177:
25:
117:
147:
587:
A San
Francisco-based company named Audentes Therapeutics is currently investigating the treatment of Crigler–Najjar syndrome with one of their gene replacement therapy products, AT342. Preliminary success has been found in early stages of a phase 1/2 clinical trial.
570:
is seen. Drug-induced cases typically regress after discontinuation of the substance. Physiological neonatal jaundice may peak at 85–170 μmol/L and decline to normal adult concentrations within two weeks. Prematurity results in higher levels.
1034:
1019:
243:
Signs and symptoms of
Crigler–Najjar syndrome include jaundice, diarrhea, vomiting, fever, confusion, slurred speech, difficulty swallowing, change in gait, staggering, frequent falling and seizures.
419:
is effective, generally with a decrease of at least 25% in serum bilirubin. In fact, this can be used, along with these other factors, to differentiate type I and II.
255:). UGT1A1 normally catalyzes the conjugation of bilirubin and glucuronic acid within hepatocytes. Conjugated bilirubin is more water-soluble and is excreted in bile.
1407:
393:
Bilirubin levels are generally below 345 μmol/L (range 100–430 μmol/L ; thus, overlap may sometimes occur), and some cases are only detected later in life.
1239:
1187:
35:
675:
96:
68:
689:
75:
603:
1180:
402:
is pigmented, instead of pale in type I or dark as normal, and monoconjugates constitute the largest fraction of bile conjugates.
82:
948:
Crigler JF Jr, Najjar VA (February 1952). "Congenital familial nonhemolytic jaundice with kernicterus; a new clinical entity".
64:
219:
This syndrome is divided into types I and II, with the latter sometimes called Arias syndrome. These two types, along with
891:"Lifelong elimination of hyperbilirubinemia in the Gunn rat with a single injection of helper-dependent adenoviral vector"
1049:
336:(bilirubin encephalopathy) or survived until early adulthood with clear neurological impairment. Today, therapy includes
1412:
1173:
848:
Fox IJ, Chowdhury JR, Kaufman SS, Goertzen TC, Chowdhury NR, Warkentin PI, Dorko K, Sauter BV, Strom SC (May 1998).
54:
473:
235:
defects in bilirubin metabolism. Unlike
Gilbert's syndrome, only a few cases of Crigler–Najjar syndrome are known.
1273:
819:
736:
325:
limited to the bilirubin-specific A1 exon; their conjugation defect is mostly restricted to bilirubin itself.
1322:
1308:
1156:
1143:
448:
89:
1244:
251:
It is caused by abnormalities in the gene coding for uridine diphosphoglucuronate glucuronosyltransferase (
1357:
541:
286:
Intense jaundice appears in the first days of life and persists thereafter. Type 1 is characterised by a
50:
651:
1377:
224:
725:
1293:
43:
405:
UGT1A1 is present at reduced but detectable levels (typically <10% of normal), because of single
176:
1214:
1063:
477:
806:
747:
1422:
1269:
39:
889:
Toietta G, Mane VP, Norona WS, Finegold MJ, Ng P, Mcdonagh AF, Beaudet AL, Lee B (March 2005).
1103:
1347:
623:
366:
340:
317:(2 to 5), and have difficulties conjugating several additional substrates (several drugs and
220:
902:
556:
1152:
8:
1417:
1303:
1038:
627:
481:
383:
369:
before the onset of brain damage and before phototherapy becomes ineffective at later age
213:
1139:
906:
784:
353:
1125:
1043:
925:
890:
579:
Plasmapheresis and phototherapy are used for treatment. Liver transplant is curative.
1210:
1074:
965:
957:
930:
871:
776:
669:
606:(UDPGT), is an animal model for the study of Crigler–Najjar syndrome. Since only one
591:
One 10-year-old girl with
Crigler–Najjar syndrome type I was successfully treated by
436:
428:
161:
788:
1298:
920:
910:
861:
768:
547:
1114:
759:
Jansen PL (December 1999). "Diagnosis and management of
Crigler–Najjar syndrome".
1264:
1068:
850:"Treatment of the Crigler–Najjar syndrome type I with hepatocyte transplantation"
310:
291:
866:
849:
714:
268:
This is a very rare disease (estimated at 0.6–1.0 per million live births), and
1382:
988:
895:
Proceedings of the
National Academy of Sciences of the United States of America
523:
488:
444:
349:
228:
1079:
1028:
1401:
983:
961:
518:
416:
306:
269:
1165:
915:
737:
https://my.clevelandclinic.org/health/diseases/22949-crigler-najjar-syndrome
208:, which results in high levels of unconjugated bilirubin and often leads to
1160:
1147:
969:
934:
780:
611:
508:
452:
440:
329:
287:
272:
increases the risk of this condition (other rare diseases may be present).
875:
1098:
456:
333:
318:
290:
bilirubin usually above 345 μmol/L (range 310–755 μmol/L ) (whereas the
273:
209:
1011:
614:
for
Crigler-Najjar is a theoretical option which is being investigated.
1120:
772:
592:
389:
However, type II differs from type I in a number of different aspects:
190:
170:
166:
53:
if you can. Unsourced or poorly sourced material may be challenged and
1327:
1219:
1205:
1109:
567:
563:
531:
527:
469:
409:
406:
322:
280:
277:
202:
194:
154:
827:
726:
https://medlineplus.gov/genetics/condition/crigler-najjar-syndrome/
599:
537:
514:
498:
494:
363:
phosphate and carbonate to form complexes with bilirubin in the gut
232:
205:
560:
396:
Because of lower serum bilirubin, kernicterus is rare in type II.
360:
302:
1057:
1054:
1023:
807:
https://rarediseases.org/rare-diseases/crigler-najjar-syndrome/
748:
https://rarediseases.org/rare-diseases/crigler-najjar-syndrome/
607:
432:
313:. Most patients (type IA) have a mutation in one of the common
298:
462:
Hyperbilirubinemia of the unconjugated type may be caused by:
314:
216:
manner. The annual incidence is estimated at 1 in 1,000,000.
16:
Rare inherited disorder affecting the metabolism of bilirubin
146:
1196:
847:
399:
198:
888:
820:"AT342 – Crigler-Najjar Syndrome – Audentes Therapeutics"
555:
In
Crigler–Najjar syndrome and Gilbert syndrome, routine
201:
in red blood cells. The disorder results in a form of non
305:
tissue. Hence, there is no response to treatment with
356:(although the effect of the drug decreases over time)
1001:
626:(1919 – May 13, 2018), an American pediatrician and
1265:
Gunther disease/congenital erythropoietic porphyria
947:
321:). A smaller percentage of patients (type IB) have
1399:
690:"Crigler-Najjar Syndrome Symptoms and Treatment"
803:National Organization for Rare Disorders (NORD)
696:. University of Pittsburgh Medical Center. 2023
630:(1914–2002), a Lebanese-American pediatrician.
197:, a chemical formed from the breakdown of the
49:Please review the contents of the article and
1195:
1181:
715:https://www.ncbi.nlm.nih.gov/books/NBK562171/
1408:Syndromes affecting the hepatobiliary system
352:inhibitors to reduce transient worsening of
674:: CS1 maint: numeric names: authors list (
382:Crigler–Najjar syndrome types I and II are
189:is a rare inherited disorder affecting the
1188:
1174:
175:
145:
924:
914:
865:
758:
604:uridine diphosphate glucuronyltransferase
423:
950:American Journal of Diseases of Children
566:usually is normal, too. No evidence for
1400:
294:for total bilirubin is 2–14 μmol/L ).
1169:
238:
650:RESERVED, INSERM US14-- ALL RIGHTS.
649:
645:
643:
18:
854:The New England Journal of Medicine
652:"Orphanet: Crigler Najjar syndrome"
13:
301:expression can be detected in the
212:. The disorder is inherited in an
14:
1434:
997:
694:Children's Hospital of Pittsburgh
640:
474:hemolytic disease of the newborn
343:in the immediate neonatal period
299:UDP glucuronosyltransferase 1-A1
115:
23:
1153:Crigler–Najjar syndrome, type 2
1140:Crigler–Najjar syndrome, type 1
976:
941:
882:
841:
431:may develop in the presence of
1274:Hepatoerythropoietic porphyria
812:
795:
761:European Journal of Pediatrics
752:
741:
730:
719:
708:
682:
51:add the appropriate references
1:
1323:Hereditary hyperbilirubinemia
1309:Erythropoietic protoporphyria
633:
449:hypertrophic pyloric stenosis
1245:Acute intermittent porphyria
574:
546:Crigler–Najjar syndrome and
378:The inheritance patterns of
258:
7:
867:10.1056/NEJM199805143382004
622:The condition is named for
582:
328:Before the availability of
36:reliable medical references
10:
1439:
415:Therefore, treatment with
373:
1413:Heme metabolism disorders
1366:
1336:
1321:
1294:Hereditary coproporphyria
1282:
1253:
1228:
1204:
1089:
1005:
801:Crigler Najjar Syndrome.
617:
602:, which lacks the enzyme
346:12 hours/day phototherapy
332:, these children died of
263:
231:, make up the five known
160:
153:
144:
136:
131:
65:"Crigler–Najjar syndrome"
42:or relies too heavily on
478:hereditary spherocytosis
246:
1358:Lucey–Driscoll syndrome
1353:Crigler–Najjar syndrome
1270:Porphyria cutanea tarda
1126:Crigler–Najjar syndrome
916:10.1073/pnas.0500930102
610:is working improperly,
542:Lucey–Driscoll syndrome
513:physiological neonatal
311:CYP450 enzyme induction
210:brain damage in infants
187:Crigler–Najjar syndrome
132:Crigler–Najjar syndrome
1378:Dubin–Johnson syndrome
424:Differential diagnosis
225:Dubin–Johnson syndrome
624:John Fielding Crigler
466:increased production
367:liver transplantation
341:exchange transfusions
1231:early mitochondrial:
1199:metabolism disorders
767:(Suppl 2): S89–S94.
557:liver function tests
505:decreased clearance
1304:Variegate porphyria
1285:late mitochondrial:
907:2005PNAS..102.3930T
628:Victor Assad Najjar
482:sickle cell disease
384:autosomal recessive
214:autosomal recessive
1348:Gilbert's syndrome
1090:External resources
824:www.audentestx.com
773:10.1007/PL00014330
354:hyperbilirubinemia
239:Signs and symptoms
221:Gilbert's syndrome
1395:
1394:
1391:
1390:
1317:
1316:
1135:
1134:
595:transplantation.
526:such as advanced
429:Neonatal jaundice
184:
183:
126:Medical condition
124:
123:
100:
1430:
1371:
1341:
1334:
1333:
1299:Harderoporphyria
1287:
1258:
1233:
1226:
1225:
1190:
1183:
1176:
1167:
1166:
1003:
1002:
991:
980:
974:
973:
945:
939:
938:
928:
918:
886:
880:
879:
869:
845:
839:
838:
836:
835:
826:. Archived from
816:
810:
799:
793:
792:
756:
750:
745:
739:
734:
728:
723:
717:
712:
706:
705:
703:
701:
686:
680:
679:
673:
665:
663:
662:
647:
559:are normal, and
548:Gilbert syndrome
180:
179:
149:
129:
128:
119:
118:
110:
107:
101:
99:
58:
27:
26:
19:
1438:
1437:
1433:
1432:
1431:
1429:
1428:
1427:
1398:
1397:
1396:
1387:
1367:
1362:
1337:
1325:
1313:
1283:
1278:
1254:
1249:
1229:
1217:
1209:
1200:
1194:
1136:
1131:
1130:
1085:
1084:
1014:
1000:
995:
994:
981:
977:
946:
942:
887:
883:
846:
842:
833:
831:
818:
817:
813:
800:
796:
757:
753:
746:
742:
735:
731:
724:
720:
713:
709:
699:
697:
688:
687:
683:
667:
666:
660:
658:
648:
641:
636:
620:
598:The homozygous
585:
577:
493:massive tissue
426:
376:
309:, which causes
292:reference range
266:
261:
249:
241:
174:
127:
120:
116:
111:
105:
102:
59:
48:
44:primary sources
28:
24:
17:
12:
11:
5:
1436:
1426:
1425:
1423:Rare syndromes
1420:
1415:
1410:
1393:
1392:
1389:
1388:
1386:
1385:
1383:Rotor syndrome
1380:
1374:
1372:
1364:
1363:
1361:
1360:
1355:
1350:
1344:
1342:
1331:
1319:
1318:
1315:
1314:
1312:
1311:
1306:
1301:
1296:
1290:
1288:
1280:
1279:
1277:
1276:
1267:
1261:
1259:
1251:
1250:
1248:
1247:
1242:
1240:ALAD porphyria
1236:
1234:
1223:
1215:erythropoietic
1202:
1201:
1193:
1192:
1185:
1178:
1170:
1164:
1163:
1150:
1133:
1132:
1129:
1128:
1117:
1106:
1094:
1093:
1091:
1087:
1086:
1083:
1082:
1071:
1060:
1046:
1031:
1015:
1010:
1009:
1007:
1006:Classification
999:
998:External links
996:
993:
992:
975:
940:
901:(11): 3930–5.
881:
860:(20): 1422–6.
840:
811:
794:
751:
740:
729:
718:
707:
681:
638:
637:
635:
632:
619:
616:
584:
581:
576:
573:
553:
552:
551:
550:
544:
534:
524:liver diseases
521:
511:
503:
502:
501:
491:
489:erythropoiesis
485:
445:hypothyroidism
425:
422:
421:
420:
413:
403:
397:
394:
375:
372:
371:
370:
364:
357:
350:heme oxygenase
347:
344:
265:
262:
260:
257:
248:
245:
240:
237:
229:Rotor syndrome
182:
181:
164:
158:
157:
151:
150:
142:
141:
138:
134:
133:
125:
122:
121:
114:
112:
31:
29:
22:
15:
9:
6:
4:
3:
2:
1435:
1424:
1421:
1419:
1416:
1414:
1411:
1409:
1406:
1405:
1403:
1384:
1381:
1379:
1376:
1375:
1373:
1370:
1365:
1359:
1356:
1354:
1351:
1349:
1346:
1345:
1343:
1340:
1339:unconjugated:
1335:
1332:
1329:
1324:
1320:
1310:
1307:
1305:
1302:
1300:
1297:
1295:
1292:
1291:
1289:
1286:
1281:
1275:
1271:
1268:
1266:
1263:
1262:
1260:
1257:
1252:
1246:
1243:
1241:
1238:
1237:
1235:
1232:
1227:
1224:
1221:
1216:
1212:
1207:
1203:
1198:
1191:
1186:
1184:
1179:
1177:
1172:
1171:
1168:
1162:
1161:Rare Diseases
1159:'s Office of
1158:
1154:
1151:
1149:
1148:Rare Diseases
1146:'s Office of
1145:
1141:
1138:
1137:
1127:
1123:
1122:
1118:
1116:
1112:
1111:
1107:
1105:
1101:
1100:
1096:
1095:
1092:
1088:
1081:
1077:
1076:
1072:
1070:
1066:
1065:
1061:
1059:
1056:
1052:
1051:
1047:
1045:
1041:
1040:
1036:
1032:
1030:
1026:
1025:
1021:
1017:
1016:
1013:
1008:
1004:
990:
989:Who Named It?
986:
985:
979:
971:
967:
963:
959:
956:(2): 259–60.
955:
951:
944:
936:
932:
927:
922:
917:
912:
908:
904:
900:
896:
892:
885:
877:
873:
868:
863:
859:
855:
851:
844:
830:on 2019-02-11
829:
825:
821:
815:
808:
804:
798:
790:
786:
782:
778:
774:
770:
766:
762:
755:
749:
744:
738:
733:
727:
722:
716:
711:
695:
691:
685:
677:
671:
657:
656:www.orpha.net
653:
646:
644:
639:
631:
629:
625:
615:
613:
609:
605:
601:
596:
594:
589:
580:
572:
569:
565:
562:
558:
549:
545:
543:
539:
535:
533:
529:
525:
522:
520:
516:
512:
510:
507:
506:
504:
500:
496:
492:
490:
486:
483:
479:
475:
471:
468:
467:
465:
464:
463:
460:
458:
454:
450:
446:
442:
438:
434:
430:
418:
417:phenobarbital
414:
411:
408:
404:
401:
398:
395:
392:
391:
390:
387:
385:
381:
368:
365:
362:
358:
355:
351:
348:
345:
342:
339:
338:
337:
335:
331:
326:
324:
320:
316:
312:
308:
307:phenobarbital
304:
300:
295:
293:
289:
284:
282:
279:
275:
271:
270:consanguinity
256:
254:
244:
236:
234:
230:
226:
222:
217:
215:
211:
207:
204:
200:
196:
192:
188:
178:
172:
168:
165:
163:
159:
156:
152:
148:
143:
139:
135:
130:
113:
109:
98:
95:
91:
88:
84:
81:
77:
74:
70:
67: –
66:
62:
61:Find sources:
56:
52:
46:
45:
41:
37:
32:This article
30:
21:
20:
1368:
1352:
1338:
1284:
1256:cytoplasmic:
1255:
1230:
1119:
1108:
1097:
1073:
1062:
1048:
1033:
1018:
982:
978:
953:
949:
943:
898:
894:
884:
857:
853:
843:
832:. Retrieved
828:the original
823:
814:
802:
797:
764:
760:
754:
743:
732:
721:
710:
698:. Retrieved
693:
684:
659:. Retrieved
655:
621:
612:gene therapy
597:
590:
586:
578:
554:
536:breast milk
509:drug-induced
487:ineffective
461:
453:galactosemia
441:hypoglycemia
427:
388:
379:
377:
330:phototherapy
327:
296:
285:
267:
252:
250:
242:
218:
186:
185:
103:
93:
86:
79:
72:
60:
40:verification
33:
1369:conjugated:
1099:MedlinePlus
519:prematurity
457:fructosemia
334:kernicterus
319:xenobiotics
274:Inheritance
137:Other names
34:needs more
1418:Hepatology
1402:Categories
1121:Patient UK
1075:DiseasesDB
834:2019-03-09
661:2021-03-10
634:References
593:liver cell
233:hereditary
191:metabolism
171:hepatology
167:Pediatrics
106:March 2022
76:newspapers
1328:bilirubin
1220:porphyrin
1206:Porphyria
1110:eMedicine
962:0096-8994
575:Treatment
568:hemolysis
564:histology
532:cirrhosis
528:hepatitis
499:hematomas
497:or large
470:hemolysis
410:mutations
407:base pair
323:mutations
281:recessive
278:autosomal
259:Diagnosis
203:hemolytic
195:bilirubin
162:Specialty
155:Bilirubin
970:14884759
935:15753292
805:. 2016;
789:24242888
781:10603107
670:cite web
600:Gunn rat
583:Research
538:jaundice
515:jaundice
495:necrosis
206:jaundice
1211:hepatic
1115:med/476
1069:D003414
984:synd/86
903:Bibcode
876:9580649
700:17 June
561:hepatic
472:(e.g.,
459:, etc.
437:hypoxia
374:Type II
361:calcium
90:scholar
55:removed
1104:001127
1058:606785
1055:218800
968:
960:
933:
926:554836
923:
874:
787:
779:
618:Eponym
608:enzyme
433:sepsis
264:Type I
253:UGT1A1
227:, and
173:
92:
85:
78:
71:
63:
1044:277.4
1029:E80.5
785:S2CID
359:oral
315:exons
303:liver
288:serum
247:Cause
97:JSTOR
83:books
1213:and
1197:Heme
1080:3176
1064:MeSH
1050:OMIM
1039:9-CM
966:PMID
958:ISSN
931:PMID
872:PMID
777:PMID
702:2023
676:link
540:and
517:and
400:Bile
380:both
199:heme
69:news
38:for
1157:NIH
1155:at
1144:NIH
1142:at
1035:ICD
1020:ICD
987:at
921:PMC
911:doi
899:102
862:doi
858:338
769:doi
765:158
530:or
297:No
276:is
193:of
140:CNS
1404::
1124::
1113::
1102::
1078::
1067::
1053::
1042::
1027::
1024:10
964:.
954:83
952:.
929:.
919:.
909:.
897:.
893:.
870:.
856:.
852:.
822:.
783:.
775:.
763:.
692:.
672:}}
668:{{
654:.
642:^
480:,
476:,
455:,
451:,
447:,
443:,
439:,
435:,
386:.
283:.
223:,
169:,
57:.
1330:)
1326:(
1272:/
1222:)
1218:(
1208:,
1189:e
1182:t
1175:v
1037:-
1022:-
1012:D
972:.
937:.
913::
905::
878:.
864::
837:.
809:.
791:.
771::
704:.
678:)
664:.
484:)
412:.
108:)
104:(
94:·
87:·
80:·
73:·
47:.
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
