950:
very strictly to a diet, in general monitored on a day-to-day basis by a specialist metabolic dietitian. In many cases, as the fetus' liver begins to develop and produce PAH normally, the mother's blood Phe levels will drop, requiring an increased intake to remain within the safe range of 2â6 mg/dL. The mother's daily Phe intake may double or even triple by the end of the pregnancy, as a result. When maternal blood Phe levels fall below 2 mg/dL, anecdotal reports indicate that the mothers may experience adverse effects, including headaches, nausea, hair loss, and general malaise. When low phenylalanine levels are maintained for the duration of pregnancy, there are no elevated levels of risk of birth defects compared with a baby born to a non-PKU mother.
383:
likely to develop neurological problems or have seizures and intellectual disability (though such clinical disorders are still possible including asthma, eczema, anemia, weight gain, renal insufficiency, osteoporosis, gastritis, esophagus, and kidney deficiencies, kidney stones, and hypertension). Additionally, major depressive disorders occur 230% higher than controls; dizziness and giddiness occur 180% higher; chronic ischemic heart disease, asthma, diabetes, and gastroenteritis occur 170% higher; and stress and adjustment disorders occur 160% higher. In general, however, outcomes for people treated for PKU are good. Treated people may have no detectable physical, neurological, or developmental problems at all.
631:
735:
49:
1240:, Følling saw a young woman named Borgny Egeland. She had two children, Liv and Dag, who had been normal at birth but subsequently developed intellectual disability. When Dag was about a year old, the mother noticed a strong smell to his urine. Følling obtained urine samples from the children and, after many tests, he found that the substance causing the odor in the urine was phenylpyruvic acid. The children, he concluded, had excess phenylpyruvic acid in the urine, the condition which came to be called phenylketonuria (PKU).
686:
305:
392:
908:
CGMP is a peptide ensures that the absorption rate of its amino acids is prolonged compared to free amino acids and thereby results in improved protein retention and increased satiety compared to free amino acids. Another important benefit of CGMP is that the taste is significantly improved when CGMP substitutes part of the free amino acids and this may help ensure improved compliance to the PKU diet.
825:, and other grain-based foods, which contain a significant amount of Phe. Many fruits and vegetables are lower in Phe and can be eaten in larger quantities. Infants may still be breastfed to provide all of the benefits of breastmilk, but the quantity must also be monitored and supplementation for missing nutrients will be required. The sweetener
516:
are able to tolerate larger amounts of phenylalanine in their diets. Without dietary intervention, mild HPA patients have blood Phe levels higher than those with normal PAH activity. There is currently no international consensus on the definition of mild HPA, however, it is most frequently diagnosed at blood Phe levels between 2â6 mg/dL.
3991:
Mild oxidation of the purified substance produced a compound which smelled of benzoic acid, leading Følling to postulate that the compound was phenylpyruvic acid.3 There was no change in the melting point upon mixing of the unknown compound with phenylpyruvic acid thus confirming the mystery compound
1200:
The average number of new cases of PKU varies in different human populations. United States
Caucasians are affected at a rate of 1 in 10,000. Turkey has the highest documented rate in the world, with 1 in 2,600 births, while countries such as Finland and Japan have extremely low rates with fewer than
859:
Supplementary "protein substitute" formulas are typically prescribed for people PKU (starting in infancy) to provide the amino acids and other necessary nutrients that would otherwise be lacking in a low-phenylalanine diet. Tyrosine, which is normally derived from phenylalanine and which is necessary
816:
are generally acceptable in controlled amounts, but the quantity of Phe consumed from these foods must be monitored. A corn-free diet may be prescribed in some cases. A food diary is usually kept to record the amount of Phe consumed with each meal, snack, or drink. An "exchange" system can be used to
718:
PKU is not curable. However, if it is diagnosed early enough, an affected newborn can grow up with normal brain development by managing and controlling phenylalanine ("Phe") levels through diet, or a combination of diet and medication. If dietary treatment is not initiated within 2 weeks after birth,
2818:
Opladen T, LĂłpez-Laso E, Cortès-Saladelafont E, Pearson TS, Sivri HS, Yildiz Y, Assmann B, Kurian MA, Leuzzi V, Heales S, Pope S, Porta F, GarcĂa-Cazorla A, HonzĂk T, Pons R, Regal L, Goez H, Artuch R, Hoffmann GF, Horvath G, ThĂśny B, Scholl-BĂźrgi S, Burlina A, Verbeek MM, Mastrangelo M, Friedman J,
1294:
introduced the newborn screening test for PKU in the early 1960s. With the knowledge that PKU could be detected before symptoms were evident, and treatment initiated, screening was quickly adopted around the world. Ireland was the first country to introduce a national screening programme in
February
515:
PAH deficiency causes a spectrum of disorders, including classic phenylketonuria (PKU) and mild hyperphenylalaninemia (also known as "hyperphe" or "mild HPA"), a less severe accumulation of phenylalanine. Compared to classic PKU patients, patients with "hyperphe" have greater PAH enzyme activity and
949:
In most countries, women with PKU who wish to have children are advised to lower their blood Phe levels (typically to between 2 and 6 mg/dL) before they become pregnant, and carefully control their levels throughout the pregnancy. This is achieved by performing regular blood tests and adhering
907:
Another treatment strategy is casein glycomacropeptide (CGMP), which is a milk peptide naturally free of Phe in its pure form CGMP can substitute for the main part of the free amino acids in the PKU diet and provides several beneficial nutritional effects compared to free amino acids. The fact that
864:
from releasing Phe stored in the muscles and other tissues into the blood. Many PKU patients have their highest Phe levels after a period of fasting (such as overnight) because fasting triggers catabolism. A diet that is low in phenylalanine but does not include protein substitutes may also fail to
527:(LNAAT). If phenylalanine is in excess in the blood, it will saturate the transporter. Excessive levels of phenylalanine tend to decrease the levels of other LNAAs in the brain. As these amino acids are necessary for protein and neurotransmitter synthesis, Phe buildup hinders the development of the
945:
For women with PKU, it is important for the health of their children to maintain low Phe levels before and during pregnancy. Though the developing fetus may only be a carrier of the PKU gene, the intrauterine environment can have very high levels of phenylalanine, which can cross the placenta. The
488:
When phenylalanine (Phe) cannot be metabolized by the body, a typical diet that would be healthy for people without PKU causes abnormally high levels of Phe to accumulate in the blood, which is toxic to the brain. If left untreated (and often even in treatment), complications of PKU include severe
335:
Because the mother's body is able to break down phenylalanine during pregnancy, infants with PKU are normal at birth. The disease is not detectable by physical examination at that time, because no damage has yet been done. Newborn screening is performed to detect the disease and initiate treatment
415:
are required for an individual to experience symptoms of the disease. For a child to inherit PKU, both parents must have and pass on the defective gene. If both parents are carriers for PKU, there is a 25% chance any child they have will be born with the disorder, a 50% chance the child will be a
382:
The damage done to the brain if PKU is untreated during the first months of life is not reversible. It is critical to control the diet of infants with PKU very carefully so that the brain has an opportunity to develop normally. Affected children who are detected at birth and treated are much less
727:
People who follow the prescribed dietary treatment from birth may (but not always) have no symptoms. Their PKU would be detectable only by a blood test. People must adhere to a special diet low in Phe for optimal brain development. Since Phe is necessary for the synthesis of many proteins, it is
1462:
or 'PAL'), which is an enzyme substitution therapy in which the missing PAH enzyme is replaced with an analogous enzyme that also breaks down Phe. PEG-PAL was in Phase 2 clinical development as of 2015, but was put on clinical hold in
September 2021. In February 2022, the FDA issued a statement
3837:
Borg C, Mondot S, Mestre M, Cavero I (November 1991). "Nicorandil: differential contribution of K+ channel opening and guanylate cyclase stimulation to its vasorelaxant effects on various endothelin-1-contracted arterial preparations. Comparison to aprikalim (RP 52891) and nitroglycerin".
1243:
His analysis of the urine of the two affected siblings led him to request many physicians near Oslo to test the urine of other affected patients. This led to the discovery of the same substance he had found in eight other patients. He conducted tests and found reactions that gave rise to
1232:
in 1934 when he noticed hyperphenylalaninemia (HPA) was associated with intellectual disability. In Norway, this disorder is known as Følling's disease, named after its discoverer. Følling was one of the first physicians to apply detailed chemical analysis to the study of disease.
262:, meaning that both copies of the gene must be mutated for the condition to develop. There are two main types, classic PKU and variant PKU, depending on whether any enzyme function remains. Those with one copy of a mutated gene typically do not have symptoms. Many countries have
538:
Recent research suggests that neurocognitive, psychosocial, quality of life, growth, nutrition, bone pathology are slightly suboptimal even for patients who are treated and maintain their Phe levels in the target range, if their diet is not supplemented with other amino acids.
4110:
Kasper DC, Ratschmann R, Metz TF, Mechtler TP, MĂśslinger D, Konstantopoulou V, Item CB, Pollak A, Herkner KR (2010). "The
National Austrian Newborn Screening Program â Eight years experience with mass spectrometry. Past, present, and future goals".
4203:
van
Wegberg AM, MacDonald A, Ahring K, BĂŠlanger-Quintana A, Blau N, Bosch AM, Burlina A, Campistol J, Feillet F, GiĹźewska M, Huijbregts SC, Kearney S, Leuzzi V, Maillot F, Muntau AC, van Rijn M, Trefz F, Walter JH, van Spronsen FJ (October 2017).
591:
can be supplemented as treatment. Those with this form of hyperphenylalaninemia may have a deficiency of tyrosine (which is created from phenylalanine by PAH), in which case treatment is supplementation of tyrosine to account for this deficiency.
343:
If a child is not diagnosed during the routine newborn screening test and a phenylalanine-restricted diet is not introduced, then phenylalanine levels in the blood will increase over time. Toxic levels of phenylalanine (and insufficient levels of
3504:
Rouse B, Azen C, Koch R, Matalon R, Hanley W, de la Cruz F, Trefz F, Friedman E, Shifrin H (1997). "Maternal phenylketonuria collaborative study (MPKUCS) offspring: Facial anomalies, malformations, and early neurological sequelae".
360:, a carboxylic acid produced by the oxidation of phenylacetone). In most cases, a repeat test should be done at approximately two weeks of age to verify the initial test and uncover any phenylketonuria that was initially missed.
542:
Classic PKU affects myelination and white matter tracts in untreated infants; this may be one major cause of neurological problems associated with phenylketonuria. Differences in white matter development are observable with
1299:
4330:
Burgard P, Ullrich K, Ballhausen D, Hennermann JB, Hollak CE, Langeveld M, Karall D, Konstantopoulou V, Maier EM, Lang F, Lachmann R, Murphy E, Garbade S, Hoffmann GF, KĂślker S, Lindner M, Zschocke J (September 2017).
697:
panel of many countries, with varied detection techniques. Most babies born in Europe, North
America, and Australia are screened for PKU soon after birth. Screening for PKU is done with bacterial inhibition assay
4548:
4529:
4514:
946:
child may develop congenital heart disease, growth retardation, microcephaly and intellectual disability as a result. PKU-affected women themselves are not at risk of additional complications during pregnancy.
865:
lower blood Phe levels, since a nutritionally insufficient diet may also trigger catabolism. For all these reasons, the prescription formula is an important part of the treatment for patients with classic PKU.
817:
calculate the amount of Phe in a portion of food from the protein content identified on a nutritional information label. Lower-protein "medical food" substitutes are often used in place of normal
2689:
Adler-Abramovich L, Vaks L, Carny O, Trudler D, Magno A, Caflisch A, Frenkel D, Gazit E (August 2012). "Phenylalanine assembly into toxic fibrils suggests amyloid etiology in phenylketonuria".
3113:"CFR â Code of Federal Regulations, Title 21, Part 172: Food additives permitted for direct addition to food for human consumption. Subpart I â Multipurpose Additives; Sec. 172.804 Aspartame"
860:
for normal brain function, is usually supplemented. Consumption of the protein substitute formulas can actually reduce phenylalanine levels, probably because it stops the process of protein
911:
Furthermore, CGMP contains a high amount of the Phe-lowering LNAAs, which constitutes about 41 g per 100 g protein and will therefore help maintain plasma Phe levels in the target range.
657:. If this reaction does not take place, phenylalanine accumulates and tyrosine is deficient. Excessive phenylalanine can be metabolized into phenylketones through the minor route, a
3963:
4482:
1205:
population with an extremely high incidence of PKU (one case in 40 births) due to extensive inbreeding. It is the most common amino acid metabolic problem in the United
Kingdom.
277:. The diet should begin as soon as possible after birth and be continued for life. People who are diagnosed early and maintain a strict diet can have normal health and a normal
2548:
Enns GM, Koch R, Brumm V, Blakely E, Suter R, Jurecki E (1 October 2010). "Suboptimal outcomes in patients with PKU treated early with diet alone: Revisiting the evidence".
5513:
5503:
634:
Pathophysiology of phenylketonuria, which is due to the absence of functional phenylalanine hydroxylase (classical subtype) or functional enzymes for the recycling of
851:
Different people can tolerate different amounts of Phe in their diet. Regular blood tests are used to determine the effects of dietary Phe intake on blood Phe level.
677:. Elevated levels of phenylalanine in the blood and detection of phenylketones in the urine is diagnostic, however most patients are diagnosed via newborn screening.
1213:
Before the causes of PKU were understood, PKU caused severe disability in most people who inherited the relevant mutations. Nobel and
Pulitzer Prize winning author
4698:
508:(PAH), which converts the amino acid phenylalanine ("Phe") to other essential compounds in the body, in particular tyrosine. Tyrosine is a conditionally essential
904:
into the brain. Its use is limited in the US due to the cost but is available in most countries as part of a low protein / PHE diet to replace missing nutrients.
3542:
2425:
Regier DS, Greene CL (July 25, 1993). "Phenylalanine
Hydroxylase Deficiency". In Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJ, Gripp KW, Amemiya A (eds.).
2114:"Clinical burden of illness in patients with phenylketonuria (PKU) and associated comorbidities - a retrospective study of German health insurance claims data"
1586:
363:
Untreated children often fail to attain early developmental milestones, develop microcephaly, and demonstrate progressive impairment of cerebral function.
1500:
269:
Treatment is with a diet that (1) is low in foods that contain phenylalanine, and which (2) includes special supplements. Babies should use a special
2939:
2163:
2098:
3412:
Michals-Matalon K (February 2008). "Sapropterin dihydrochloride, 6-R-L-erythro-5,6,7,8-tetrahydrobiopterin, in the treatment of phenylketonuria".
489:
intellectual disability, brain function abnormalities, microcephaly, mood disorders, irregular motor functioning, and behavioral problems such as
4779:
3887:
Følling A (1 January 1934). "Ăber
Ausscheidung von Phenylbrenztraubensäure in den Harn als Stoffwechselanomalie in Verbindung mit Imbezillität".
3623:
DiLella AG, Kwok SC, Ledley FD, Marvit J, Woo SL (1986). "Molecular structure and polymorphic map of the human phenylalanine hydroxylase gene".
749:
or equivalently 2 to 6 mg/dL. This is optimally to be achieved during at least the first 10 years, to allow the brain to develop normally.
258:
responsible for the metabolism of excess phenylalanine. This results in the buildup of dietary phenylalanine to potentially toxic levels. It is
5165:
5026:
4984:
340:, typically performed 2â7 days after birth. This test can reveal elevated phenylalanine levels after one or two days of normal infant feeding.
3914:
Centerwall SA, Centerwall WR (2000). "The discovery of phenylketonuria: the story of a young couple, two affected children, and a scientist".
3098:
4887:
1707:
5049:
4691:
4443:
453:
Carriers of a single PKU allele do not exhibit symptoms of the disease but appear to be protected to some extent against the fungal toxin
5347:
4784:
3056:
476:
in the bands 12q22-q24.2. As of 2000, around 400 disease-causing mutations had been found in the PAH gene. This is an example of allelic
3518:
1831:
1862:
1749:
554:
diseases, such as Alzheimer's disease and Parkinson's disease, due to the formation of toxic amyloid-like assemblies of phenylalanine.
1221:
Many untreated PKU patients born before widespread newborn screening are still alive, largely in dependent living homes/institutions.
324:. It may also result in a musty smell and lighter skin. A baby born to a mother who has poorly treated PKU may have heart problems, a
229:. It may also result in a musty smell and lighter skin. A baby born to a mother who has poorly treated PKU may have heart problems, a
900:) may compete with phe for specific carrier proteins that transport LNAAs across the intestinal mucosa into the blood and across the
3740:
5498:
5388:
1217:
had a daughter named Carol who lived with PKU before treatment was available, and wrote an account of its effects in a book called
547:. Abnormalities in gray matter can also be detected, particularly in the motor and pre-motor cortex, thalamus and the hippocampus.
490:
2905:
4684:
3330:"Breakfast with glycomacropeptide compared with amino acids suppresses plasma ghrelin levels in individuals with phenylketonuria"
1953:
Berry SA, Brown C, Grant M, Greene CL, Jurecki E, Koch J, Moseley K, Suter R, van Calcar SC, Wiles J, Cederbaum S (August 2013).
288:
Phenylketonuria affects about 1 in 12,000 babies. Males and females are affected equally. The disease was discovered in 1934 by
5493:
4711:
4421:
4392:
3818:
FerĂĄk V, SivĂĄkovĂĄ D, SieglovĂĄ Z (1987). "SlovenskĂ CigĂĄni (RĂłmovia) â populĂĄcia s najvyĹĄĹĄĂm koeficientom inbrĂdingu v EurĂłpe".
1923:
1769:
1547:
375:
are major clinical problems later in life. A characteristic "musty or mousy" odor on the skin, as well as a predisposition for
2177:
5362:
5357:
3074:
2315:
2210:
5279:
3281:"Improved nutritional management of phenylketonuria by using a diet containing glycomacropeptide compared with amino acids"
3873:
719:
the child is likely to develop permanent intellectual disability, even if dietary interventions begin shortly thereafter.
501:
Classical PKU, and its less severe forms "mild PKU" and "mild hyperphenylalaninemia" are caused by a mutated gene for the
5508:
5115:
4563:
1876:
Martinez M, Harding CO, Schwank G, ThĂśny B (January 2024). "State-of-the-art 2023 on gene therapy for phenylketonuria".
3539:
4867:
4487:
4013:
2358:
1856:
1825:
1743:
619:. By contrast, in classical PKU (without dihydrobiopterin involvement), prolactin levels would be relatively normal.
348:) can interfere with infant development in ways that have permanent effects. The disease may present clinically with
3112:
1700:"National Institutes of Health Consensus Development Conference Statement Phenylketonuria: Screening and Management"
5488:
5366:
3716:
1578:
1291:
5170:
4086:
1486:
1298:
In 2017, the European Guidelines were published. They were called for by the patient organizations such as the
769:
569:
563:
512:
for PKU patients because without PAH it cannot be produced in the body through the breakdown of phenylalanine.
5415:
5383:
5251:
2376:"Psychiatric and Cognitive Aspects of Phenylketonuria: The Limitations of Diet and Promise of New Treatments"
493:, as well as physical symptoms such as a "musty" odor, eczema, and unusually light skin and hair coloration.
461:
suggested that this accounted for the persistence of the allele in certain populations, in that it confers a
2501:"Large neutral amino acids block phenylalanine transport into brain tissue in patients with phenylketonuria"
630:
572:, which occurs when the PAH enzyme is normal, and a defect is found in the biosynthesis or recycling of the
5054:
1667:
5457:
4789:
1459:
829:, present in many diet foods and soft drinks, must also be avoided, as aspartame contains phenylalanine.
282:
165:
4664:
5523:
5447:
5426:
5098:
4707:
2632:
Hawks Z, Hood AM, Lerman-Sinkoff DB, Shimony JS, Rutlin J, Lagoni D, Grange DK, White DA (2019-01-01).
544:
203:
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5342:
5059:
5031:
4799:
1229:
643:
505:
431:
289:
263:
251:
141:
3779:
Bickel, H., Bachmann, C., Beckers, R., Brandt, N.J., Clayton, B.E., Corrado, G, et al. (1981).
4746:
4741:
4574:
3090:
703:
3064:
1699:
868:
Evidence supports dietary supplementation with large neutral amino acids (LNAAs). The LNAAs (e.g.
706:(MS/MS). Measurements done using MS/MS determine the concentration of Phe and the ratio of Phe to
5247:
4912:
4403:
3065:
Behrman, Richard E., Kliegman, Robert, Nelson, Waldo E., Karen Marcdante, Jenson, Hal B. (2006).
1455:
901:
573:
532:
520:
424:
313:
218:
89:
2111:
1668:"Press Announcements - FDA approves a new treatment for PKU, a rare and serious genetic disease"
5518:
5241:
5110:
4892:
2821:"Consensus guideline for the diagnosis and treatment of tetrahydrobiopterin (BH4) deficiencies"
2769:"Consensus guideline for the diagnosis and treatment of tetrahydrobiopterin (BH4) deficiencies"
466:
368:
4614:
3658:
Lee DH, Koo SK, Lee KS, Yeon YJ, Oh HJ, Kim SW, Lee SJ, Kim SS, Lee JE, Jo I, Jung SC (2004).
3053:
2348:
2056:
1815:
923:
which metabolizes phenylalanine. It is for adults who are poorly managed on other treatments.
5396:
4831:
4523:
4372:
2157:
2092:
1846:
1733:
742:
734:
702:), immunoassays using fluorometric or photometric detection, or amino acid measurement using
477:
473:
4281:"Requirements for a minimum standard of care for phenylketonuria: the patients' perspective"
4156:"The Manchester regional screening programme: A 10-year exercise in patient and family care"
2870:
Michals K, Matalon R (1985). "Phenylalanine metabolites, attention span and hyperactivity".
519:
Phenylalanine is a large, neutral amino acid (LNAA). LNAAs compete for transport across the
5257:
5207:
4962:
4719:
2634:"White and gray matter brain development in children and young adults with phenylketonuria"
1765:"ADHD symptoms in neurometabolic diseases: Underlying mechanisms and clinical implications"
1492:
837:
622:
As of 2020, tetrahydrobiopterin deficiency was known to result from defects in five genes.
608:
404:
396:
356:(excessively fair hair and skin), and a "musty odor" to the baby's sweat and urine (due to
296:
that aim to directly restore liver PAH activity are a promising and active research field.
20:
3279:
van Calcar SC, MacLeod EL, Gleason ST, Etzel MR, Clayton MK, Wolff JA, Ney DM (Apr 2009).
2002:
1275:
and John Gerrard published a paper that described how they created a diet that was low in
416:
carrier and a 25% chance the child will neither develop nor be a carrier for the disease.
8:
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4631:
4552:
3762:
3748:
2600:
2340:
1476:
926:
746:
635:
600:
576:
434:(PAH), rendering it nonfunctional. This enzyme is necessary to metabolize the amino acid
372:
337:
259:
128:
4676:
1630:
5197:
5120:
5087:
4756:
4307:
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3481:
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3437:
3394:
3354:
3329:
3305:
3280:
3209:
3184:
3160:
3136:"Does a single plasma phenylalanine predict the quality of control in phenylketonuria?"
3135:
3031:
2998:
2967:
Longo N (2022). "Chapter 420: Inherited Disorders of Amino Acid Metabolism in Adults".
2847:
2820:
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2633:
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2584:
2476:
2451:
2402:
2375:
2283:
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2140:
2113:
2059:"Prevalence of comorbid conditions among adult patients diagnosed with phenylketonuria"
1979:
1954:
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1735:
Nutrition Management of Inherited Metabolic Diseases: Lessons from Metabolic University
1639:
1614:
1315:
1261:
83:
4557:
4349:
4332:
2525:
2500:
2112:
Trefz KF, Muntau AC, Kohlscheen KM, Altevers J, Jacob C, Braun S, et al. (2019).
840:
in people with phenylalanine hydroxylase deficiency. Thus, in addition to the careful
5467:
4939:
4585:
4354:
4312:
4279:
Hagedorn TS, van Berkel P, Hammerschmidt G, LhotĂĄkovĂĄ M, Saludes RP (December 2013).
4237:
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3640:
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3522:
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3214:
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2800:
2741:
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2671:
2653:
2614:
2565:
2530:
2481:
2432:
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2311:
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2206:
2145:
2080:
1984:
1905:
1893:
1852:
1821:
1800:
1788:
1739:
1644:
1287:
694:
666:
462:
458:
442:(Tyr). When PAH activity is reduced, phenylalanine accumulates and is converted into
357:
136:
63:
4429:
4140:
4063:
3943:
3804:
3693:
2753:
2057:
Burton BK, Jones KB, Cederbaum S, Rohr F, Waisbren S, Irwin DE, et al. (2018).
1931:
1783:
1764:
1539:
1300:
European Society for Phenylketonuria and Allied Disorders Treated as Phenylketonuria
738:
Warning for people with phenylketonuria on a label for an aspartame-containing drink
5422:
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5285:
5102:
5077:
4625:
4407:
4344:
4302:
4292:
4227:
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3671:
3632:
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3514:
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3468:
3421:
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3341:
3300:
3292:
3248:
3204:
3196:
3183:
van Spronsen FJ, de Groot MJ, Hoeksma M, Reijngoud DJ, van Rijn M (December 2010).
3155:
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2832:
2790:
2780:
2733:
2698:
2661:
2645:
2604:
2596:
2557:
2520:
2512:
2471:
2463:
2397:
2387:
2332:
2278:
2242:
2135:
2125:
2070:
2036:
1974:
1966:
1901:
1885:
1778:
1634:
1626:
1339:
1280:
1225:
408:
353:
329:
234:
152:
68:
48:
4255:
2585:"Age-related gray matter volume changes in the brain during non-elderly adulthood"
5410:
5405:
5237:
4957:
4761:
4579:
4477:
4377:
4046:
4029:
3546:
3060:
2344:
1763:
Cannon Homaei S, Barone H, Kleppe R, Betari N, Reif A, Haavik J (November 2021).
1272:
321:
226:
97:
3345:
2561:
2467:
2374:
Ashe K, Kelso W, Farrand S, Panetta J, Fazio T, De Jong G, Walterfang M (2019).
2075:
2058:
5317:
5271:
5082:
5021:
4751:
4628:
3865:
2837:
2785:
2649:
1237:
1179:
1009:
805:
797:
765:
674:
670:
443:
270:
4653:
4642:
4590:
4542:
4538:
4222:
4206:"The complete European guidelines on phenylketonuria: diagnosis and treatment"
4124:
3676:
3659:
3425:
3200:
2130:
5482:
5352:
5211:
5144:
4999:
4472:
3778:
3022:
2657:
2499:
Pietz J, Kreis R, Rupp A, Mayatepek E, Rating D, Boesch C, Bremer HJ (1999).
2450:
de la Parra A, GarcĂa MI, Waisbren SE, Cornejo V, Raimann E (December 2015).
2426:
2392:
2247:
2230:
1897:
1332:
1276:
1257:
1214:
1202:
1189:
662:
650:
435:
364:
214:
56:
4297:
4096:
3472:
3296:
3253:
3236:
3185:"Large neutral amino acids in the treatment of PKU: from theory to practice"
2883:
2224:
2222:
1458:
is conducting clinical trials to investigate PEG-PAL (PEGylated recombinant
5188:
5004:
4934:
4929:
4872:
4358:
4316:
4241:
4202:
4171:
4132:
4055:
4003:
3986:
3935:
3685:
3609:
3519:
10.1002/(SICI)1096-8628(19970303)69:1<89::AID-AJMG17>3.0.CO;2-K
3490:
3457:"Maternal phenylketonuria: report from the United Kingdom Registry 1978â97"
3433:
3363:
3314:
3262:
3218:
3040:
2856:
2817:
2804:
2745:
2710:
2675:
2618:
2569:
2534:
2485:
2436:
2411:
2149:
2084:
1988:
1909:
1792:
1648:
1449:
1268:
1249:
1245:
777:
699:
658:
454:
325:
293:
230:
4422:"BioMarin : Pipeline : Pipeline Overview : BMN 165 for PKU"
3927:
3851:
3644:
3526:
3169:
2891:
2702:
2292:
1955:"Newborn screening 50 years later: access issues faced by adults with PKU"
685:
638:(new variant subtype) utilized in the first step of the metabolic pathway.
281:. Effectiveness is monitored through periodic blood tests. The medication
5337:
5180:
4648:
4609:
4189:
3151:
2935:
2219:
1279:
and the patient recovered. Bickel, Gerrard and Hickmans were awarded the
1119:
1099:
1089:
781:
728:
required for appropriate growth, but levels must be strictly controlled.
528:
274:
4278:
3636:
2999:"Phenylketonuria in Children and Mothers: Genes, Environments, Behavior"
1970:
1286:
PKU was the first disorder to be routinely diagnosed through widespread
1201:
one case of PKU in 100,000 births. A 1987 study from Slovakia reports a
752:
The diet requires restricting or eliminating foods high in Phe, such as
5431:
5400:
5192:
5069:
5041:
4809:
4723:
4637:
4079:
Robert Guthrie--the PKU story : crusade against mental retardation
4004:
Marelene Rayner-Canham, Geoff Rayner-Canham (2008), "Evelyn Hickmans",
3796:
2737:
1889:
920:
889:
881:
877:
861:
773:
647:
509:
420:
211:
207:
169:
160:
72:
4506:
2819:
Wassenberg T, Jeltsch K, KulhĂĄnek J, Kuseyri HĂźbschmann O (May 2020).
557:
5327:
4976:
4972:
4921:
4907:
4620:
3767:
2350:
The Molecular and Genetic Basis of Neurologic and Psychiatric Disease
2028:
1481:
1464:
969:
930:
897:
885:
826:
757:
616:
278:
176:
76:
42:
Phenylalanine hydroxylase deficiency, PAH deficiency, Følling disease
3390:
3182:
2516:
603:
is required to convert Phe to Tyr and is required to convert Tyr to
5322:
5267:
5233:
5221:
5148:
5135:
4883:
4841:
4659:
4006:
Chemistry was Their Life: Pioneer British Women Chemists, 1880â1949
2724:
Surtees R, Blau N (2000). "The neurochemistry of phenylketonuria".
1139:
873:
833:
785:
753:
707:
689:
Blood is taken from a two-week-old baby to test for phenylketonuria
654:
612:
596:
588:
439:
427:
345:
304:
246:
241:
124:
4329:
1295:
1966, Austria also started screening in 1966 and England in 1968.
336:
before any damage is done. The blood sample is usually taken by a
5225:
4949:
4879:
4854:
4845:
4771:
1253:
1059:
1029:
1019:
869:
789:
551:
349:
317:
222:
93:
4568:
4444:"BioMarin Provides Updates on Progress in Gene Therapy Programs"
4153:
2688:
2449:
391:
5013:
4732:
4533:
4518:
4491:
4397:
1762:
1326:
1320:
1169:
1159:
1129:
1109:
1039:
989:
979:
893:
809:
801:
761:
604:
502:
412:
376:
255:
3959:"Phenylketonuria: an inborn error of phenylalanine metabolism"
3584:"Phenylketonuria: an inborn error of phenylalanine metabolism"
2631:
2330:
1423:
1381:
1366:
1348:
292:, with the importance of diet determined in 1935. As of 2023,
3328:
MacLeod EL, Clayton MK, van Calcar SC, Ney DM (August 2010).
3278:
3134:
MacDonald A, Rylance GW, Asplin D, Hall SK, Booth IW (1998).
1149:
1079:
1069:
1049:
999:
934:
822:
818:
813:
587:
is necessary for proper activity of the enzyme PAH, and this
447:
4109:
3741:"Philippine Society for Orphan Disorders â Current Registry"
1615:"Phenylketonuria: a review of current and future treatments"
155:
low in foods that contain phenylalanine; special supplements
3327:
1875:
1463:
requiring further data from non-clinical studies to assess
1432:
1399:
1387:
1384:
1372:
1354:
793:
524:
446:(also known as phenylketone), which can be detected in the
3133:
1378:
1252:, which led him to conclude that the compound contained a
4706:
4154:
Komrower GM, Sardharwalla IB, Fowler B, Bridge C (1979).
3840:
The Journal of Pharmacology and Experimental Therapeutics
1851:. Springer Science & Business Media. pp. 89â92.
1411:
2582:
1496:, which features a character who has mental retardation.
4027:
3622:
3454:
3377:
Burton BK, Kar S, Kirkpatrick P (2008). "Sapropterin".
2984:
Pediatric Endocrinology and Inborn Errors of Metabolism
2498:
2373:
1579:"What are common treatments for phenylketonuria (PKU)?"
1264:, which indicated that the substance was in the urine.
379:, persist throughout life in the absence of treatment.
250:
gene, which can result in inefficient or nonfunctional
3956:
3836:
3581:
919:
In 2018, the FDA approved an enzyme substitute called
4333:"Issues with European guidelines for phenylketonuria"
4081:. Pasadena, Calif.: Hope Pub. House. pp. 65â66.
3817:
3582:
Williams RA, Mamotte CD, Burnett JR (February 2008).
2452:"Cognitive functioning in mild hyperphenylalaninemia"
1952:
1820:(7 ed.). Elsevier Health Sciences. p. 150.
1612:
1420:
1408:
1402:
1396:
1393:
1363:
1360:
1351:
1345:
1342:
4496:
3913:
3889:
Hoppe-Seyler's Zeitschrift fĂźr Physiologische Chemie
3503:
3376:
2547:
1429:
1414:
1369:
1357:
599:
can be used to distinguish between these two types.
5514:
Biology of attention deficit hyperactivity disorder
5504:
Skin conditions resulting from errors in metabolism
3660:"The molecular basis of phenylketonuria in Koreans"
2203:
Andrews' Diseases of the Skin: clinical Dermatology
1448:Other therapies are under investigation, including
1375:
558:
Tetrahydrobiopterin-deficient hyperphenylalaninemia
244:genetic disorder. It is caused by mutations in the
2981:
4839:
3781:"Neonatal mass screening for metabolic disorders"
2929:
2766:
1813:
1731:
933:of phenylalanine) when taken by mouth can reduce
5480:
4147:
4103:
3577:
3575:
3455:Lee PJ, Ridout D, Walter JH, Cockburn F (2005).
3237:"Manufacture and use of dairy protein fractions"
615:. Low levels of dopamine lead to high levels of
550:It was recently suggested that PKU may resemble
4780:3-hydroxy-3-methylglutaryl-CoA lyase deficiency
3573:
3571:
3569:
3567:
3565:
3563:
3561:
3559:
3557:
3555:
3411:
3274:
3272:
3230:
3228:
3115:. US Food and Drug Administration. 1 April 2018
2583:Terribilli D, Schaufelberger MS (10 May 2020).
2310:. Chicago, IL: Wm. C. Brown. pp. 247â248.
2267:"The heterozygote advantage in phenylketonuria"
5166:6-Pyruvoyltetrahydropterin synthase deficiency
3755:
2869:
2228:
1305:
1302:. They have received some critical reception.
411:. As an autosomal recessive disorder, two PKU
4692:
4028:Mitchell JJ, Trakadis YJ, Scriver CR (2011).
3657:
2178:"Phenylketonuria (PKU) - Symptoms and causes"
745:(or "target ranges") are between 120 and 360
5050:2-Methylbutyryl-CoA dehydrogenase deficiency
3957:Williams RA, Mamotte CD, Burnett JR (2008).
3552:
3405:
3321:
3269:
3225:
2986:. New York: McGraw Hill Medical. p. 26.
2811:
2541:
2424:
2162:: CS1 maint: multiple names: authors list (
2105:
2097:: CS1 maint: multiple names: authors list (
2050:
1848:Teratology in the Twentieth Century Plus Ten
1662:
1660:
1658:
1613:Al Hafid N, Christodoulou J (October 2015).
5348:Carbamoyl phosphate synthetase I deficiency
4785:3-Methylcrotonyl-CoA carboxylase deficiency
3003:Current Directions in Psychological Science
2982:Sarafoglou K, Hoffmann GF, Roth KS (eds.).
2723:
2200:
1573:
1571:
1569:
1567:
1565:
848:to ensure that nutritional needs are met.
4699:
4685:
3285:The American Journal of Clinical Nutrition
2975:
2969:Harrison's Principles of Internal Medicine
1727:
1725:
937:levels of this amino acid in some people.
854:
47:
19:"PKU" redirects here. For other uses, see
4348:
4306:
4296:
4231:
4221:
4179:
4045:
4021:
3976:
3675:
3599:
3480:
3353:
3304:
3252:
3208:
3159:
3030:
2846:
2836:
2794:
2784:
2665:
2608:
2524:
2475:
2456:Molecular Genetics and Metabolism Reports
2401:
2391:
2299:
2282:
2246:
2139:
2129:
2074:
1978:
1782:
1694:
1692:
1690:
1688:
1655:
1638:
1534:
1532:
1530:
1528:
1526:
1524:
1522:
1520:
1518:
1503:, a movie version of Flowers for Algernon
568:A rarer form of hyperphenylalaninemia is
4481:) is being considered for deletion. See
4337:The Lancet. Diabetes & Endocrinology
3234:
1608:
1606:
1604:
1562:
733:
684:
629:
491:attention deficit hyperactivity disorder
390:
371:abnormalities, and seizures, and severe
303:
5027:Isobutyryl-CoA dehydrogenase deficiency
3886:
3880:
3414:Expert Opinion on Investigational Drugs
2996:
2971:(21st ed.). New York: McGraw Hill.
2767:Opladen T, LĂłpez-Laso E (26 May 2020).
2194:
1722:
5481:
4853:
4030:"Phenylalanine hydroxylase deficiency"
3189:Journal of Inherited Metabolic Disease
2872:American Journal of Clinical Nutrition
2353:. Butterworth-Heinemann. p. 820.
1878:Journal of Inherited Metabolic Disease
1844:
1838:
1770:Neuroscience and Biobehavioral Reviews
1732:Bernstein LE, Rohr F, Helm JR (2015).
1685:
1515:
1224:Phenylketonuria was discovered by the
5363:Ornithine transcarbamylase deficiency
5358:N-Acetylglutamate synthase deficiency
4680:
3866:"NPKUA > Education > About PKU"
3711:
3709:
3707:
3705:
3703:
2966:
2962:
2960:
2958:
2956:
2492:
2431:. University of Washington, Seattle.
2305:
2261:
2255:
1601:
914:
710:, the ratio will be elevated in PKU.
625:
299:
5280:Dopamine beta hydroxylase deficiency
4654:Phenylalanine Hydroxylase Deficiency
4076:
3997:
3507:American Journal of Medical Genetics
2601:10.1016/j.neurobiolaging.2009.02.008
2009:. Madriella Network. 14 October 2016
525:large neutral amino acid transporter
308:Abnormally small head (microcephaly)
5116:Methylmalonyl-CoA mutase deficiency
3533:
3105:
2906:"Phenylketonuria (PKU) - Diagnosis"
1710:from the original on 5 October 2016
1631:10.3978/j.issn.2224-4336.2015.10.07
1589:from the original on 5 October 2016
1467:resulting from PEG-PAL treatments.
611:. L-DOPA, in turn, is converted to
430:in the gene for the hepatic enzyme
395:Phenylketonuria is inherited in an
13:
3700:
2953:
2271:American Journal of Human Genetics
2229:Gonzalez J, Willis MS (Feb 2010).
483:
14:
5535:
4868:Glutathione synthetase deficiency
4485:to help reach a consensus. âş
4464:
4285:Orphanet Journal of Rare Diseases
4210:Orphanet Journal of Rare Diseases
4008:, World Scientific, p. 198,
3334:Molecular Genetics and Metabolism
2825:Orphanet Journal of Rare Diseases
2773:Orphanet Journal of Rare Diseases
2550:Molecular Genetics and Metabolism
2505:Journal of Clinical Investigation
1814:Marcdante K, Kliegman RM (2014).
1550:from the original on 27 July 2016
1256:ring. Further testing showed the
3876:from the original on 2015-01-01.
3588:The Clinical Biochemist. Reviews
3461:Archives of Disease in Childhood
3140:Archives of Disease in Childhood
3101:from the original on 2015-05-05.
3091:"Foods highest in Phenylalanine"
3015:10.1111/j.1467-8721.2009.01604.x
2930:Mayo Clinic Staff (2007-12-20).
1865:from the original on 2017-09-11.
1834:from the original on 2017-09-11.
1752:from the original on 2017-09-11.
1338:
844:of Phe in the diet, Tyr must be
693:PKU is commonly included in the
496:
5499:Amino acid metabolism disorders
4436:
4414:
4385:
4365:
4323:
4272:
4248:
4196:
4070:
3964:The Clinical Biochemist Reviews
3950:
3907:
3858:
3830:
3811:
3772:
3733:
3717:"PKU: Closing the Gaps in Care"
3651:
3616:
3549:Genetics and Louisiana Families
3497:
3448:
3370:
3176:
3127:
3083:
3067:Nelson essentials of pediatrics
3047:
2990:
2942:from the original on 2008-03-17
2923:
2898:
2863:
2760:
2717:
2682:
2625:
2576:
2443:
2418:
2367:
2324:
2170:
2021:
1995:
1946:
1916:
1869:
1817:Nelson Essentials of Pediatrics
1784:10.1016/j.neubiorev.2021.11.012
953:
5171:Tetrahydrobiopterin deficiency
4378:Merriam-Webster.com Dictionary
4113:Wiener Klinische Wochenschrift
3992:was indeed phenylpyruvic acid.
3901:10.1515/bchm2.1934.227.1-4.169
3785:European Journal of Pediatrics
2726:European Journal of Pediatrics
1807:
1756:
1487:Tetrahydrobiopterin deficiency
570:tetrahydrobiopterin deficiency
564:Tetrahydrobiopterin deficiency
1:
5494:Autosomal recessive disorders
5416:Lysinuric protein intolerance
4790:3-Methylglutaconic aciduria 1
4470:
4350:10.1016/S2213-8587(17)30201-2
3379:Nature Reviews Drug Discovery
1508:
1283:in 1962 for their discovery.
16:Amino acid metabolic disorder
5055:Beta-ketothiolase deficiency
4047:10.1097/GIM.0b013e3182141b48
2201:James WD, Berger TG (2006).
1924:"Phenylketonuria (PKU) Test"
713:
680:
467:heterozygote is advantageous
217:. Untreated PKU can lead to
181:Normal health with treatment
7:
5458:Ethylmalonic encephalopathy
4256:"Consensus Paper - E.S.PKU"
3820:BratislavskĂŠ LekĂĄrske Listy
3346:10.1016/j.ymgme.2010.04.003
2562:10.1016/j.ymgme.2010.05.017
2468:10.1016/j.ymgmr.2015.10.009
2076:10.1016/j.ymgme.2018.09.006
1470:
1460:phenylalanine ammonia lyase
1443:
1306:Etymology and pronunciation
472:The PAH gene is located on
386:
320:, behavioral problems, and
283:sapropterin dihydrochloride
225:, behavioral problems, and
166:Sapropterin dihydrochloride
10:
5540:
5509:Disorders causing seizures
5448:2-Hydroxyglutaric aciduria
5427:Oculocerebrorenal syndrome
2838:10.1186/s13023-020-01379-8
2786:10.1186/s13023-020-01379-8
2650:10.1016/j.nicl.2019.101916
1208:
940:
929:(BH4) (a cofactor for the
561:
545:magnetic resonance imaging
312:Untreated PKU can lead to
264:newborn screening programs
206:that results in decreased
204:inborn error of metabolism
142:Newborn screening programs
18:
5453:Aminoacylase 1 deficiency
5440:
5382:
5343:Argininosuccinic aciduria
5312:
5302:
5266:
5252:HermanskyâPudlak syndrome
5220:
5179:
5156:
5143:
5133:
5096:
5068:
5060:Maple syrup urine disease
5040:
5032:Maple syrup urine disease
5012:
4997:
4971:
4948:
4920:
4905:
4830:
4808:
4800:Maple syrup urine disease
4770:
4731:
4718:
4600:
4500:
4223:10.1186/s13023-017-0685-2
4125:10.1007/s00508-010-1457-3
3677:10.1007/s10038-004-0197-5
3664:Journal of Human Genetics
3426:10.1517/13543784.17.2.245
3201:10.1007/s10545-010-9216-1
2997:Widaman KF (2009-02-01).
2131:10.1186/s13023-019-1153-y
1219:The Child Who Never Grew.
963:
960:
808:. Starchy foods, such as
644:phenylalanine hydroxylase
506:phenylalanine hydroxylase
465:âin other words, being a
432:phenylalanine hydroxylase
252:phenylalanine hydroxylase
185:
175:
159:
148:
135:
120:
112:
104:
82:
62:
55:
46:
38:
33:
4742:Glutaric acidemia type 1
4483:templates for discussion
3241:The Journal of Nutrition
2393:10.3389/fpsyt.2019.00561
2248:10.1309/LM62LVV5OSLUJOQF
1738:. Springer. p. 91.
1619:Translational Pediatrics
704:tandem mass spectrometry
438:(Phe) to the amino acid
419:PKU is characterized by
5489:Intellectual disability
5248:Oculocutaneous albinism
4404:Oxford University Press
4298:10.1186/1750-1172-8-191
4160:British Medical Journal
3473:10.1136/adc.2003.037762
3297:10.3945/ajcn.2008.27280
2932:"Phenylketonuria (PKU)"
2691:Nature Chemical Biology
2007:Madriella Doula Network
2003:"Phenylketonuria (PKU)"
1706:. October 16â18, 2000.
1544:Genetics Home Reference
855:Nutritional supplements
722:
533:intellectual disability
314:intellectual disability
285:may be useful in some.
273:with a small amount of
219:intellectual disability
96:, behavioral problems,
90:intellectual disability
5367:translocase deficiency
5111:Methylmalonic acidemia
4893:Glycine encephalopathy
4172:10.1136/bmj.2.6191.635
2231:"Ivar AsbjÜrn Følling"
2037:Wishart Research Group
739:
690:
665:. Metabolites include
646:normally converts the
639:
400:
309:
240:Phenylketonuria is an
5397:Solute carrier family
4712:amino acid metabolism
4400:UK English Dictionary
3928:10.1542/peds.105.1.89
3254:10.1093/jn/134.4.996S
3235:Etzel MR (Apr 2004).
3069:. Elsevier/Saunders.
2884:10.1093/ajcn/42.2.361
2703:10.1038/nchembio.1002
2589:Neurobiology of Aging
2205:. Saunders Elsevier.
1546:. September 8, 2016.
743:Optimal health ranges
737:
688:
633:
478:genetic heterogeneity
425:compound heterozygous
394:
373:learning disabilities
307:
189:~1 in 12,000 newborns
5258:Waardenburg syndrome
5208:Tyrosinemia type III
4963:Prolidase deficiency
4034:Genetics in Medicine
3152:10.1136/adc.78.2.122
3054:Chapter 55, page 255
2638:NeuroImage: Clinical
1959:Genetics in Medicine
1493:Flowers for Algernon
1230:Ivar Asbjørn Følling
653:into the amino acid
609:tyrosine hydroxylase
290:Ivar Asbjørn Følling
21:PKU (disambiguation)
5463:Fumarase deficiency
5203:Tyrosinemia type II
4863:D-Glyceric acidemia
4818:Hypertryptophanemia
4795:Isovaleric acidemia
3637:10.1021/bi00352a001
2439:– via PubMed.
2235:Laboratory Medicine
2118:Orphanet J Rare Dis
1971:10.1038/gim.2013.10
1477:Hyperphenylalanemia
1336:; it is pronounced
927:Tetrahydrobiopterin
902:bloodâbrain barrier
636:tetrahydrobiopterin
601:Tetrahydrobiopterin
577:tetrahydrobiopterin
521:bloodâbrain barrier
463:selective advantage
405:autosomal recessive
397:autosomal recessive
260:autosomal recessive
129:autosomal recessive
5198:Tyrosinemia type I
5121:Propionic acidemia
5088:Hypermethioninemia
4757:Pipecolic acidemia
4601:External resources
4448:BioMarin Investors
4381:. Merriam-Webster.
4119:(21â22): 607â613.
3922:(1 Pt 1): 89â103.
3797:10.1007/BF00441305
3545:2008-04-08 at the
3059:2016-05-11 at the
2738:10.1007/PL00014370
1890:10.1002/jimd.12651
1262:phenylpyruvic acid
1260:to be the same as
915:Enzyme substitutes
740:
691:
640:
626:Metabolic pathways
401:
310:
300:Signs and symptoms
88:Without treatment
5524:Newborn screening
5476:
5475:
5468:Trimethylaminuria
5378:
5377:
5374:
5373:
5298:
5297:
5294:
5293:
5129:
5128:
4993:
4992:
4940:Urocanic aciduria
4901:
4900:
4826:
4825:
4674:
4673:
4393:"Phenylketonuria"
4373:"Phenylketonuria"
4166:(6191): 635â638.
3247:(4): 996Sâ1002S.
3076:978-1-4160-0159-1
2380:Front. Psychiatry
2317:978-0-697-24030-9
2212:978-0-7216-2921-6
2029:"Phenylketonuria"
1845:Kalter H (2010).
1540:"phenylketonuria"
1288:newborn screening
1198:
1197:
695:newborn screening
294:genetic therapies
266:for the disease.
193:
192:
144:in many countries
137:Diagnostic method
28:Medical condition
5531:
5423:Fanconi syndrome
5310:
5309:
5286:Brunner syndrome
5154:
5153:
5141:
5140:
5078:Cystathioninuria
5010:
5009:
4918:
4917:
4851:
4850:
4837:
4836:
4729:
4728:
4701:
4694:
4687:
4678:
4677:
4498:
4497:
4458:
4457:
4455:
4454:
4440:
4434:
4433:
4428:. Archived from
4418:
4412:
4411:
4406:. Archived from
4389:
4383:
4382:
4369:
4363:
4362:
4352:
4327:
4321:
4320:
4310:
4300:
4276:
4270:
4269:
4267:
4266:
4252:
4246:
4245:
4235:
4225:
4200:
4194:
4193:
4183:
4151:
4145:
4144:
4107:
4101:
4100:
4074:
4068:
4067:
4049:
4025:
4019:
4018:
4001:
3995:
3994:
3980:
3954:
3948:
3947:
3911:
3905:
3904:
3895:(1â4): 169â181.
3884:
3878:
3877:
3862:
3856:
3855:
3834:
3828:
3827:
3815:
3809:
3808:
3791:(137): 133â139.
3776:
3770:
3759:
3753:
3752:
3747:. Archived from
3737:
3731:
3730:
3728:
3726:
3721:
3713:
3698:
3697:
3679:
3655:
3649:
3648:
3620:
3614:
3613:
3603:
3579:
3550:
3537:
3531:
3530:
3501:
3495:
3494:
3484:
3452:
3446:
3445:
3409:
3403:
3402:
3374:
3368:
3367:
3357:
3325:
3319:
3318:
3308:
3276:
3267:
3266:
3256:
3232:
3223:
3222:
3212:
3180:
3174:
3173:
3163:
3131:
3125:
3124:
3122:
3120:
3109:
3103:
3102:
3087:
3081:
3080:
3051:
3045:
3044:
3034:
2994:
2988:
2987:
2979:
2973:
2972:
2964:
2951:
2950:
2948:
2947:
2927:
2921:
2920:
2918:
2916:
2902:
2896:
2895:
2867:
2861:
2860:
2850:
2840:
2815:
2809:
2808:
2798:
2788:
2764:
2758:
2757:
2721:
2715:
2714:
2686:
2680:
2679:
2669:
2629:
2623:
2622:
2612:
2595:(2â6): 354â368.
2580:
2574:
2573:
2545:
2539:
2538:
2528:
2511:(8): 1169â1178.
2496:
2490:
2489:
2479:
2447:
2441:
2440:
2422:
2416:
2415:
2405:
2395:
2371:
2365:
2364:
2328:
2322:
2321:
2306:Lewis R (1997).
2303:
2297:
2296:
2286:
2259:
2253:
2252:
2250:
2226:
2217:
2216:
2198:
2192:
2191:
2189:
2188:
2174:
2168:
2167:
2161:
2153:
2143:
2133:
2109:
2103:
2102:
2096:
2088:
2078:
2054:
2048:
2047:
2045:
2043:
2025:
2019:
2018:
2016:
2014:
1999:
1993:
1992:
1982:
1950:
1944:
1943:
1941:
1939:
1930:. Archived from
1920:
1914:
1913:
1904: 10764640.
1873:
1867:
1866:
1842:
1836:
1835:
1811:
1805:
1804:
1786:
1760:
1754:
1753:
1729:
1720:
1719:
1717:
1715:
1696:
1683:
1682:
1680:
1678:
1664:
1653:
1652:
1642:
1610:
1599:
1598:
1596:
1594:
1575:
1560:
1559:
1557:
1555:
1536:
1501:1968 Film Charly
1439:
1438:
1435:
1434:
1431:
1426:
1425:
1422:
1417:
1416:
1413:
1410:
1405:
1404:
1401:
1398:
1395:
1390:
1389:
1386:
1383:
1380:
1377:
1374:
1371:
1368:
1365:
1362:
1359:
1356:
1353:
1350:
1347:
1344:
1281:John Scott Medal
958:
957:
409:genetic disorder
354:hypopigmentation
330:low birth weight
322:mental disorders
235:low birth weight
227:mental disorders
116:Classic, variant
98:mental disorders
69:Medical genetics
51:
31:
30:
5539:
5538:
5534:
5533:
5532:
5530:
5529:
5528:
5479:
5478:
5477:
5472:
5436:
5411:Iminoglycinuria
5406:Hartnup disease
5387:
5370:
5320:
5290:
5262:
5238:Ocular albinism
5216:
5175:
5158:Phenylketonuria
5125:
5092:
5064:
5036:
5003:
4989:
4967:
4958:Hyperprolinemia
4944:
4913:Îą-ketoglutarate
4911:
4897:
4888:GAMT deficiency
4822:
4804:
4766:
4762:Saccharopinuria
4735:/straight chain
4714:
4705:
4675:
4670:
4669:
4643:Phenylketonuria
4596:
4595:
4509:
4488:Phenylketonuria
4486:
4467:
4462:
4461:
4452:
4450:
4442:
4441:
4437:
4420:
4419:
4415:
4391:
4390:
4386:
4371:
4370:
4366:
4328:
4324:
4277:
4273:
4264:
4262:
4254:
4253:
4249:
4201:
4197:
4152:
4148:
4108:
4104:
4089:
4077:Koch J (1997).
4075:
4071:
4026:
4022:
4016:
4002:
3998:
3955:
3951:
3912:
3908:
3885:
3881:
3864:
3863:
3859:
3835:
3831:
3816:
3812:
3777:
3773:
3763:Phenylketonuria
3760:
3756:
3739:
3738:
3734:
3724:
3722:
3719:
3715:
3714:
3701:
3656:
3652:
3621:
3617:
3580:
3553:
3547:Wayback Machine
3538:
3534:
3502:
3498:
3453:
3449:
3410:
3406:
3391:10.1038/nrd2540
3375:
3371:
3326:
3322:
3277:
3270:
3233:
3226:
3181:
3177:
3132:
3128:
3118:
3116:
3111:
3110:
3106:
3089:
3088:
3084:
3077:
3061:Wayback Machine
3052:
3048:
2995:
2991:
2980:
2976:
2965:
2954:
2945:
2943:
2928:
2924:
2914:
2912:
2904:
2903:
2899:
2868:
2864:
2816:
2812:
2765:
2761:
2722:
2718:
2687:
2683:
2630:
2626:
2581:
2577:
2556:(2â3): 99â109.
2546:
2542:
2517:10.1172/JCI5017
2497:
2493:
2448:
2444:
2423:
2419:
2372:
2368:
2361:
2329:
2325:
2318:
2304:
2300:
2260:
2256:
2227:
2220:
2213:
2199:
2195:
2186:
2184:
2176:
2175:
2171:
2155:
2154:
2110:
2106:
2090:
2089:
2063:Mol Genet Metab
2055:
2051:
2041:
2039:
2027:
2026:
2022:
2012:
2010:
2001:
2000:
1996:
1951:
1947:
1937:
1935:
1934:on May 17, 2018
1922:
1921:
1917:
1874:
1870:
1859:
1843:
1839:
1828:
1812:
1808:
1761:
1757:
1746:
1730:
1723:
1713:
1711:
1698:
1697:
1686:
1676:
1674:
1666:
1665:
1656:
1611:
1602:
1592:
1590:
1577:
1576:
1563:
1553:
1551:
1538:
1537:
1516:
1511:
1473:
1446:
1428:
1419:
1407:
1392:
1341:
1337:
1316:combining forms
1312:phenylketonuria
1308:
1273:Evelyn Hickmans
1211:
956:
943:
917:
857:
832:The amino acid
731:
725:
716:
683:
628:
607:via the enzyme
586:
582:
566:
560:
499:
486:
484:Pathophysiology
389:
302:
196:Phenylketonuria
34:Phenylketonuria
29:
24:
17:
12:
11:
5:
5537:
5527:
5526:
5521:
5516:
5511:
5506:
5501:
5496:
5491:
5474:
5473:
5471:
5470:
5465:
5460:
5455:
5450:
5444:
5442:
5438:
5437:
5435:
5434:
5429:
5419:
5418:
5413:
5408:
5403:
5393:
5391:
5380:
5379:
5376:
5375:
5372:
5371:
5369:
5360:
5355:
5350:
5345:
5340:
5335:
5333:
5332:
5331:
5318:Hyperammonemia
5307:
5300:
5299:
5296:
5295:
5292:
5291:
5289:
5288:
5282:
5276:
5274:
5272:Norepinephrine
5264:
5263:
5261:
5260:
5255:
5245:
5230:
5228:
5218:
5217:
5215:
5214:
5205:
5200:
5195:
5185:
5183:
5177:
5176:
5174:
5173:
5168:
5162:
5160:
5151:
5138:
5131:
5130:
5127:
5126:
5124:
5123:
5118:
5113:
5107:
5105:
5094:
5093:
5091:
5090:
5085:
5083:Homocystinuria
5080:
5074:
5072:
5066:
5065:
5063:
5062:
5057:
5052:
5046:
5044:
5038:
5037:
5035:
5034:
5029:
5024:
5022:Hypervalinemia
5018:
5016:
5007:
4995:
4994:
4991:
4990:
4988:
4987:
4981:
4979:
4969:
4968:
4966:
4965:
4960:
4954:
4952:
4946:
4945:
4943:
4942:
4937:
4932:
4926:
4924:
4915:
4903:
4902:
4899:
4898:
4896:
4895:
4890:
4876:
4875:
4870:
4865:
4859:
4857:
4848:
4834:
4828:
4827:
4824:
4823:
4821:
4820:
4814:
4812:
4806:
4805:
4803:
4802:
4797:
4792:
4787:
4782:
4776:
4774:
4768:
4767:
4765:
4764:
4759:
4754:
4752:Hyperlysinemia
4749:
4744:
4738:
4736:
4726:
4716:
4715:
4704:
4703:
4696:
4689:
4681:
4672:
4671:
4668:
4667:
4656:
4645:
4634:
4632:article/947781
4617:
4605:
4604:
4602:
4598:
4597:
4594:
4593:
4582:
4571:
4560:
4545:
4526:
4510:
4505:
4504:
4502:
4501:Classification
4495:
4494:
4466:
4465:External links
4463:
4460:
4459:
4435:
4432:on 2015-01-01.
4413:
4410:on 2020-08-05.
4384:
4364:
4343:(9): 681â683.
4322:
4271:
4247:
4195:
4146:
4102:
4087:
4069:
4040:(8): 697â707.
4020:
4014:
3996:
3949:
3906:
3879:
3857:
3829:
3810:
3771:
3754:
3751:on 2015-01-04.
3732:
3699:
3670:(1): 617â621.
3650:
3631:(4): 743â749.
3615:
3551:
3532:
3496:
3467:(2): 143â146.
3447:
3404:
3385:(3): 199â200.
3369:
3320:
3291:(4): 1068â77.
3268:
3224:
3175:
3126:
3104:
3082:
3075:
3046:
2989:
2974:
2952:
2922:
2897:
2862:
2810:
2759:
2716:
2681:
2624:
2575:
2540:
2491:
2442:
2417:
2366:
2359:
2331:Rosenberg RN,
2323:
2316:
2308:Human Genetics
2298:
2254:
2241:(2): 118â119.
2218:
2211:
2193:
2169:
2104:
2069:(3): 228â234.
2049:
2020:
1994:
1945:
1915:
1868:
1857:
1837:
1826:
1806:
1755:
1744:
1721:
1684:
1654:
1600:
1585:. 2013-08-23.
1561:
1513:
1512:
1510:
1507:
1506:
1505:
1497:
1489:
1484:
1479:
1472:
1469:
1465:oncogenic risk
1445:
1442:
1307:
1304:
1292:Robert Guthrie
1238:Rikshospitalet
1210:
1207:
1196:
1195:
1192:
1186:
1185:
1182:
1180:United Kingdom
1176:
1175:
1172:
1166:
1165:
1162:
1156:
1155:
1152:
1146:
1145:
1142:
1136:
1135:
1132:
1126:
1125:
1122:
1116:
1115:
1112:
1106:
1105:
1102:
1096:
1095:
1092:
1086:
1085:
1082:
1076:
1075:
1072:
1066:
1065:
1062:
1056:
1055:
1052:
1046:
1045:
1042:
1036:
1035:
1032:
1026:
1025:
1022:
1016:
1015:
1012:
1010:Czechoslovakia
1006:
1005:
1002:
996:
995:
992:
986:
985:
982:
976:
975:
972:
966:
965:
962:
955:
952:
942:
939:
916:
913:
856:
853:
806:cottage cheese
766:chicken breast
724:
721:
715:
712:
682:
679:
675:phenethylamine
671:phenylpyruvate
627:
624:
584:
580:
562:Main article:
559:
556:
523:(BBB) via the
498:
495:
485:
482:
444:phenylpyruvate
388:
385:
301:
298:
191:
190:
187:
183:
182:
179:
173:
172:
163:
157:
156:
150:
146:
145:
139:
133:
132:
122:
118:
117:
114:
110:
109:
106:
102:
101:
86:
80:
79:
66:
60:
59:
53:
52:
44:
43:
40:
36:
35:
27:
15:
9:
6:
4:
3:
2:
5536:
5525:
5522:
5520:
5519:Rare diseases
5517:
5515:
5512:
5510:
5507:
5505:
5502:
5500:
5497:
5495:
5492:
5490:
5487:
5486:
5484:
5469:
5466:
5464:
5461:
5459:
5456:
5454:
5451:
5449:
5446:
5445:
5443:
5439:
5433:
5430:
5428:
5424:
5421:
5420:
5417:
5414:
5412:
5409:
5407:
5404:
5402:
5398:
5395:
5394:
5392:
5390:
5385:
5381:
5368:
5364:
5361:
5359:
5356:
5354:
5353:Citrullinemia
5351:
5349:
5346:
5344:
5341:
5339:
5336:
5334:
5329:
5326:
5325:
5324:
5319:
5315:
5311:
5308:
5306:
5301:
5287:
5283:
5281:
5278:
5277:
5275:
5273:
5269:
5265:
5259:
5256:
5253:
5249:
5246:
5243:
5239:
5235:
5232:
5231:
5229:
5227:
5223:
5219:
5213:
5212:Hawkinsinuria
5209:
5206:
5204:
5201:
5199:
5196:
5194:
5190:
5187:
5186:
5184:
5182:
5178:
5172:
5169:
5167:
5164:
5163:
5161:
5159:
5155:
5152:
5150:
5146:
5145:Phenylalanine
5142:
5139:
5137:
5132:
5122:
5119:
5117:
5114:
5112:
5109:
5108:
5106:
5104:
5100:
5095:
5089:
5086:
5084:
5081:
5079:
5076:
5075:
5073:
5071:
5067:
5061:
5058:
5056:
5053:
5051:
5048:
5047:
5045:
5043:
5039:
5033:
5030:
5028:
5025:
5023:
5020:
5019:
5017:
5015:
5011:
5008:
5006:
5001:
5000:propionyl-CoA
4996:
4986:
4983:
4982:
4980:
4978:
4974:
4970:
4964:
4961:
4959:
4956:
4955:
4953:
4951:
4947:
4941:
4938:
4936:
4933:
4931:
4928:
4927:
4925:
4923:
4919:
4916:
4914:
4909:
4904:
4894:
4891:
4889:
4885:
4881:
4878:
4877:
4874:
4871:
4869:
4866:
4864:
4861:
4860:
4858:
4856:
4852:
4849:
4847:
4843:
4838:
4835:
4833:
4829:
4819:
4816:
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4623:
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4073:
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4015:9781908978998
4011:
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4000:
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3984:
3979:
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3910:
3902:
3898:
3894:
3890:
3883:
3875:
3871:
3867:
3861:
3853:
3849:
3846:(2): 526â34.
3845:
3841:
3833:
3826:(2): 168â175.
3825:
3821:
3814:
3806:
3802:
3798:
3794:
3790:
3786:
3782:
3775:
3769:
3765:
3764:
3758:
3750:
3746:
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3435:
3431:
3427:
3423:
3420:(2): 245â51.
3419:
3415:
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3396:
3392:
3388:
3384:
3380:
3373:
3365:
3361:
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3316:
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3220:
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3202:
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3055:
3050:
3042:
3038:
3033:
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3024:
3020:
3016:
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3008:
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3000:
2993:
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2970:
2963:
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2926:
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2792:
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2782:
2778:
2774:
2770:
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2755:
2751:
2747:
2743:
2739:
2735:
2732:: S109âS113.
2731:
2727:
2720:
2712:
2708:
2704:
2700:
2696:
2692:
2685:
2677:
2673:
2668:
2663:
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2647:
2643:
2639:
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2434:
2430:
2429:
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2360:9780750673600
2356:
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2309:
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2280:
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2264:
2258:
2249:
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2240:
2236:
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2225:
2223:
2214:
2208:
2204:
2197:
2183:
2179:
2173:
2165:
2159:
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2147:
2142:
2137:
2132:
2127:
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2108:
2100:
2094:
2086:
2082:
2077:
2072:
2068:
2064:
2060:
2053:
2038:
2034:
2030:
2024:
2008:
2004:
1998:
1990:
1986:
1981:
1976:
1972:
1968:
1964:
1960:
1956:
1949:
1933:
1929:
1928:HealthLink BC
1925:
1919:
1911:
1907:
1903:
1899:
1895:
1891:
1887:
1883:
1879:
1872:
1864:
1860:
1858:9789048188208
1854:
1850:
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1829:
1827:9780323226981
1823:
1819:
1818:
1810:
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1798:
1794:
1790:
1785:
1780:
1776:
1772:
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1747:
1745:9783319146218
1741:
1737:
1736:
1728:
1726:
1709:
1705:
1701:
1695:
1693:
1691:
1689:
1673:
1669:
1663:
1661:
1659:
1650:
1646:
1641:
1636:
1632:
1628:
1625:(4): 304â17.
1624:
1620:
1616:
1609:
1607:
1605:
1588:
1584:
1580:
1574:
1572:
1570:
1568:
1566:
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1545:
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1531:
1529:
1527:
1525:
1523:
1521:
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1504:
1502:
1498:
1495:
1494:
1490:
1488:
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1478:
1475:
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1461:
1457:
1453:
1451:
1441:
1437:
1335:
1334:
1329:
1328:
1323:
1322:
1317:
1313:
1303:
1301:
1296:
1293:
1289:
1284:
1282:
1278:
1277:phenylalanine
1274:
1270:
1265:
1263:
1259:
1258:melting point
1255:
1251:
1247:
1241:
1239:
1234:
1231:
1227:
1222:
1220:
1216:
1215:Pearl S. Buck
1206:
1204:
1193:
1191:
1190:United States
1188:
1187:
1183:
1181:
1178:
1177:
1173:
1171:
1168:
1167:
1163:
1161:
1158:
1157:
1153:
1151:
1148:
1147:
1143:
1141:
1138:
1137:
1133:
1131:
1128:
1127:
1124:1 in 102,000
1123:
1121:
1118:
1117:
1113:
1111:
1108:
1107:
1103:
1101:
1098:
1097:
1093:
1091:
1088:
1087:
1084:1 in 125,000
1083:
1081:
1078:
1077:
1073:
1071:
1068:
1067:
1063:
1061:
1058:
1057:
1053:
1051:
1048:
1047:
1043:
1041:
1038:
1037:
1034:1 in 200,000
1033:
1031:
1028:
1027:
1023:
1021:
1018:
1017:
1013:
1011:
1008:
1007:
1003:
1001:
998:
997:
993:
991:
988:
987:
983:
981:
978:
977:
973:
971:
968:
967:
959:
951:
947:
938:
936:
932:
928:
924:
922:
912:
909:
905:
903:
899:
895:
891:
887:
883:
879:
875:
871:
866:
863:
852:
849:
847:
843:
839:
835:
830:
828:
824:
820:
815:
811:
807:
804:, and lowfat
803:
799:
795:
791:
787:
783:
779:
775:
771:
767:
763:
759:
755:
750:
748:
744:
736:
732:
729:
720:
711:
709:
705:
701:
696:
687:
678:
676:
672:
668:
667:phenylacetate
664:
661:pathway with
660:
656:
652:
651:phenylalanine
649:
645:
637:
632:
623:
620:
618:
614:
610:
606:
602:
598:
593:
590:
578:
575:
571:
565:
555:
553:
548:
546:
540:
536:
534:
530:
526:
522:
517:
513:
511:
507:
504:
497:Classical PKU
494:
492:
481:
479:
475:
474:chromosome 12
470:
468:
464:
460:
456:
451:
449:
445:
441:
437:
436:phenylalanine
433:
429:
426:
422:
417:
414:
410:
406:
398:
393:
384:
380:
378:
374:
370:
366:
365:Hyperactivity
361:
359:
358:phenylacetate
355:
351:
347:
341:
339:
333:
331:
327:
323:
319:
315:
306:
297:
295:
291:
286:
284:
280:
276:
272:
267:
265:
261:
257:
253:
249:
248:
243:
238:
236:
232:
228:
224:
220:
216:
215:phenylalanine
213:
209:
205:
201:
197:
188:
184:
180:
178:
174:
171:
167:
164:
162:
158:
154:
151:
147:
143:
140:
138:
134:
130:
126:
123:
119:
115:
111:
107:
103:
99:
95:
91:
87:
85:
81:
78:
74:
70:
67:
65:
61:
58:
57:Phenylalanine
54:
50:
45:
41:
37:
32:
26:
22:
5305:oxaloacetate
5189:Alkaptonuria
5157:
5005:succinyl-CoA
4935:Histidinemia
4930:Carnosinemia
4873:Sarcosinemia
4708:Inborn error
4658:
4647:
4636:
4619:
4608:
4584:
4573:
4562:
4547:
4528:
4513:
4476:
4451:. Retrieved
4447:
4438:
4430:the original
4425:
4416:
4408:the original
4396:
4387:
4376:
4367:
4340:
4336:
4325:
4288:
4284:
4274:
4263:. Retrieved
4259:
4250:
4213:
4209:
4198:
4163:
4159:
4149:
4116:
4112:
4105:
4078:
4072:
4037:
4033:
4023:
4005:
3999:
3990:
3971:(1): 31â41.
3968:
3962:
3952:
3919:
3915:
3909:
3892:
3888:
3882:
3869:
3860:
3843:
3839:
3832:
3823:
3819:
3813:
3788:
3784:
3774:
3761:
3757:
3749:the original
3744:
3735:
3723:. Retrieved
3667:
3663:
3653:
3628:
3625:Biochemistry
3624:
3618:
3594:(1): 31â41.
3591:
3587:
3535:
3513:(1): 89â95.
3510:
3506:
3499:
3464:
3460:
3450:
3417:
3413:
3407:
3382:
3378:
3372:
3340:(4): 303â8.
3337:
3333:
3323:
3288:
3284:
3244:
3240:
3195:(6): 671â6.
3192:
3188:
3178:
3146:(2): 122â6.
3143:
3139:
3129:
3117:. Retrieved
3107:
3094:
3085:
3066:
3049:
3009:(1): 48â52.
3006:
3002:
2992:
2983:
2977:
2968:
2944:. Retrieved
2925:
2913:. Retrieved
2909:
2900:
2878:(2): 361â5.
2875:
2871:
2865:
2828:
2824:
2813:
2776:
2772:
2762:
2729:
2725:
2719:
2697:(8): 701â6.
2694:
2690:
2684:
2641:
2637:
2627:
2592:
2588:
2578:
2553:
2549:
2543:
2508:
2504:
2494:
2459:
2455:
2445:
2428:GeneReviewsÂŽ
2427:
2420:
2386:(561): 561.
2383:
2379:
2369:
2349:
2326:
2307:
2301:
2277:(5): 773â5.
2274:
2270:
2265:(May 1986).
2257:
2238:
2234:
2202:
2196:
2185:. Retrieved
2181:
2172:
2158:cite journal
2121:
2117:
2107:
2093:cite journal
2066:
2062:
2052:
2040:. Retrieved
2032:
2023:
2011:. Retrieved
2006:
1997:
1965:(8): 591â9.
1962:
1958:
1948:
1936:. Retrieved
1932:the original
1927:
1918:
1884:(1): 80â92.
1881:
1877:
1871:
1847:
1840:
1816:
1809:
1774:
1768:
1758:
1734:
1714:12 September
1712:. Retrieved
1703:
1675:. Retrieved
1671:
1622:
1618:
1593:12 September
1591:. Retrieved
1582:
1554:12 September
1552:. Retrieved
1543:
1499:
1491:
1454:
1450:gene therapy
1447:
1331:
1325:
1319:
1311:
1309:
1297:
1285:
1269:Horst Bickel
1266:
1250:benzoic acid
1246:benzaldehyde
1242:
1235:
1223:
1218:
1212:
1199:
1194:1 in 25,000
1184:1 in 10,000
1164:1 in 20,000
1154:1 in 20,000
1114:1 in 14,500
1104:1 in 18,000
1094:1 in 41,000
1074:1 in 17,000
1054:1 in 18,300
1044:1 in 13,500
1024:1 in 12,000
1004:1 in 17,000
994:1 in 22,000
974:1 in 10,000
954:Epidemiology
948:
944:
925:
918:
910:
906:
867:
858:
850:
846:supplemented
845:
841:
831:
751:
741:
730:
726:
717:
700:Guthrie test
692:
659:transaminase
641:
621:
594:
567:
549:
541:
537:
518:
514:
500:
487:
471:
455:ochratoxin A
452:
418:
402:
381:
362:
342:
334:
311:
287:
268:
245:
239:
199:
195:
194:
100:, musty odor
25:
5338:Argininemia
5181:Tyrosinemia
4649:GeneReviews
4610:MedlinePlus
4471:âš The
3745:psod.org.ph
2936:Mayo Clinic
2910:Mayo Clinic
2341:Prusiner SB
2182:Mayo Clinic
1777:: 838â856.
1672:www.fda.gov
1236:In 1934 at
1174:1 in 2,600
1144:1 in 5,300
1134:1 in 8,000
1120:Philippines
1100:Netherlands
1064:1 in 4,500
1014:1 in 7,000
984:1 in 8,690
642:The enzyme
459:Louis Woolf
275:breast milk
105:Usual onset
39:Other names
5483:Categories
5432:Cystinosis
5401:Cystinuria
5314:Urea cycle
5193:Ochronosis
5070:Methionine
5042:Isoleucine
4810:Tryptophan
4724:acetyl-CoA
4638:Patient UK
4586:DiseasesDB
4453:2023-09-04
4291:(1): 191.
4265:2018-11-23
4216:(1): 162.
4088:0932727913
3916:Pediatrics
3540:lsuhsc.edu
2946:2008-03-13
2831:(1): 126.
2779:(1): 126.
2644:: 101916.
2345:Nestler EJ
2187:2020-03-10
2124:(1): 181.
1677:9 December
1509:References
1228:physician
964:Incidence
921:pegvaliase
862:catabolism
774:watercress
758:egg whites
648:amino acid
595:Levels of
531:, causing
510:amino acid
421:homozygous
407:metabolic
403:PKU is an
338:heel prick
326:small head
231:small head
212:amino acid
208:metabolism
170:pegvaliase
161:Medication
73:pediatrics
5389:IE of RTT
5384:Transport
5328:aspartate
5284:reverse:
4977:glutamine
4973:Glutamate
4922:Histidine
4908:glutamate
4621:eMedicine
3870:npkua.org
3768:eMedicine
3442:207475494
3399:263991793
3119:22 August
3023:0963-7214
2658:2213-1582
2462:: 72â75.
2337:DiMauro S
2333:Barchi RL
1898:0141-8955
1801:243983688
1482:Lofenalac
1310:The word
1267:In 1954,
1226:Norwegian
970:Australia
931:oxidation
842:reduction
838:essential
827:aspartame
770:spirulina
714:Treatment
681:Screening
663:glutamate
617:prolactin
428:mutations
279:life span
242:inherited
186:Frequency
177:Prognosis
149:Treatment
77:dietetics
64:Specialty
5323:arginine
5268:Tyrosine
5234:Albinism
5222:Tyrosine
5149:tyrosine
5136:fumarate
5097:General
4884:Creatine
4842:pyruvate
4660:Orphanet
4629:derm/712
4626:ped/1787
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