Case report: multiple UGT1A1 gene variants in a patient with Crigler-Najjar syndrome

Linda Gailite,Dmitrijs Rots,Ieva Pukite,Gunta Cernevska,Madara Kreile

doi:10.1186/s12887-018-1285-6

Linda Gailite, Dmitrijs Rots + Show 3 more

Open Access

https://doi.org/10.1186/s12887-018-1285-6

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Abstract

BackgroundInherited unconjugated hyperbilirubinemia is caused by variants in the gene UGT1A1 leading to Gilbert’s syndrome and Crigler-Najjar syndrome types I and II. These syndromes are differentiated on the basis of UGT1A1 residual enzymatic activity and its affected bilirubin levels and responsiveness to phenobarbital treatment.Case presentationIn this report, we present a boy with Crigler-Najjar syndrome type II with high unconjugated bilirubin levels that decreased after phenobarbital treatment but increased in adolescence. Four different UGT1A1 gene variants have been identified for this patient, of which one is novel (g.11895_11898del) most likely confirming diagnose molecularly.ConclusionsThe presented case highlights the challenges encountered with the interpretation of molecular data upon identification of multiple variants in one gene that are causing different degree reducing effect on enzyme activity leading to several clinical conditions.

Highlights

Inherited unconjugated hyperbilirubinemia is caused by variants in the gene UDP-glucuronosyltransferase 1A1 (UGT1A1) leading to Gilbert’s syndrome and Crigler-Najjar syndrome types I and II
The presented case highlights the challenges encountered with the interpretation of molecular data upon identification of multiple variants in one gene that are causing different degree reducing effect on enzyme activity leading to several clinical conditions
Inherited unconjugated hyperbilirubinemia is caused by pathogenic variants in the UGT1A1 gene and, depending on the bilirubin levels, is categorized as Gilbert’s syndrome (GS; Online Mendelian Inheritance in Man (OMIM): 143500), Crigler-Najjar syndrome type I (CNS-I; OMIM: 218800), or Crigler-Najjar syndrome type II (CNS-II; OMIM: 606785); the total bilirubin levels range from 17.1–102.6 μmol/L, 102.6–342 μmol/L, and 342–769.5 μmol/L, respectively [1]

Summary

Conclusions

The presented case highlights the challenges encountered with the interpretation of molecular data upon identification of multiple variants in one gene that are causing different degree reducing effect on enzyme activity leading to several clinical conditions

Background

Findings

Discussion and conclusions