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Case report: A rare case of pyruvate kinase deficiency and Crigler-Najjar syndrome type II with a novel pathogenic variant of PKLR and UGT1A1 mutation
Pyruvate Kinase Deficiency (PKD) and Crigler-Najjar syndrome are rare autosomal recessive liver diseases. PKD is caused by homozygous or compound heterozygous mutations in the PKLR gene, leading to non-spherocytic hereditary hemolytic anemia. On the other hand, Crigler-Najjar syndrome (CNS-II) is ch...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10475990/ https://www.ncbi.nlm.nih.gov/pubmed/37671043 http://dx.doi.org/10.3389/fgene.2023.1229271 |
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author | Wu, Huan Wu, Long Zhang, Quan Zhang, Bao-fang |
author_facet | Wu, Huan Wu, Long Zhang, Quan Zhang, Bao-fang |
author_sort | Wu, Huan |
collection | PubMed |
description | Pyruvate Kinase Deficiency (PKD) and Crigler-Najjar syndrome are rare autosomal recessive liver diseases. PKD is caused by homozygous or compound heterozygous mutations in the PKLR gene, leading to non-spherocytic hereditary hemolytic anemia. On the other hand, Crigler-Najjar syndrome (CNS-II) is characterized by the loss or reduced activity of UDP-glucuronosyltransferase, resulting in elevated levels of unconjugated bilirubin, which is the primary cause of disease manifestation. To date, there have been no reported cases of patients with both conditions. In this case report, we present the unique clinical course of a 15-year-old Chinese patient with both PKD and CNS-II. The patient was admitted for evaluation of hyperbilirubinemia and exhibited yellowish skin color, icteric sclera, and splenomegaly upon physical examination. Extensive laboratory examinations ruled out viral, hemolytic, autoimmune, and inborn or acquired metabolic etiologies of liver injury. Histopathological findings indicated benign recurrent intrahepatic cholestasis (BRIC) and hemosiderosis. Surprisingly, targeted next-generation sequencing (NGS) of the patient’s blood did not reveal any mutation sites associated with BRIC. Instead, it identified a novel homozygous pathogenic variant of the PKLR gene [c.1276C>T (p.Arg426Trp)] and a rare heterozygous variant of UGT1A1 gene [c.-55_-54insAT, c.1091C>T (p.Pro364Leu)]. These findings strongly suggest a diagnosis of PKD and CNS-II in the patient. Treatment with 500 mg/day of ursodeoxycholic acid proved to be effective, rapidly reducing the patient’s total bilirubin levels and shortening the symptomatic period. This case highlights the importance of genetic diagnosis in accurately identifying the underlying cause of hyperbilirubinemia, especially in patients with rare hereditary diseases. Furthermore, NGS can provide valuable insights into the genotype-phenotype correlation of PKD and CNS-II. |
format | Online Article Text |
id | pubmed-10475990 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-104759902023-09-05 Case report: A rare case of pyruvate kinase deficiency and Crigler-Najjar syndrome type II with a novel pathogenic variant of PKLR and UGT1A1 mutation Wu, Huan Wu, Long Zhang, Quan Zhang, Bao-fang Front Genet Genetics Pyruvate Kinase Deficiency (PKD) and Crigler-Najjar syndrome are rare autosomal recessive liver diseases. PKD is caused by homozygous or compound heterozygous mutations in the PKLR gene, leading to non-spherocytic hereditary hemolytic anemia. On the other hand, Crigler-Najjar syndrome (CNS-II) is characterized by the loss or reduced activity of UDP-glucuronosyltransferase, resulting in elevated levels of unconjugated bilirubin, which is the primary cause of disease manifestation. To date, there have been no reported cases of patients with both conditions. In this case report, we present the unique clinical course of a 15-year-old Chinese patient with both PKD and CNS-II. The patient was admitted for evaluation of hyperbilirubinemia and exhibited yellowish skin color, icteric sclera, and splenomegaly upon physical examination. Extensive laboratory examinations ruled out viral, hemolytic, autoimmune, and inborn or acquired metabolic etiologies of liver injury. Histopathological findings indicated benign recurrent intrahepatic cholestasis (BRIC) and hemosiderosis. Surprisingly, targeted next-generation sequencing (NGS) of the patient’s blood did not reveal any mutation sites associated with BRIC. Instead, it identified a novel homozygous pathogenic variant of the PKLR gene [c.1276C>T (p.Arg426Trp)] and a rare heterozygous variant of UGT1A1 gene [c.-55_-54insAT, c.1091C>T (p.Pro364Leu)]. These findings strongly suggest a diagnosis of PKD and CNS-II in the patient. Treatment with 500 mg/day of ursodeoxycholic acid proved to be effective, rapidly reducing the patient’s total bilirubin levels and shortening the symptomatic period. This case highlights the importance of genetic diagnosis in accurately identifying the underlying cause of hyperbilirubinemia, especially in patients with rare hereditary diseases. Furthermore, NGS can provide valuable insights into the genotype-phenotype correlation of PKD and CNS-II. Frontiers Media S.A. 2023-08-21 /pmc/articles/PMC10475990/ /pubmed/37671043 http://dx.doi.org/10.3389/fgene.2023.1229271 Text en Copyright © 2023 Wu, Wu, Zhang and Zhang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Wu, Huan Wu, Long Zhang, Quan Zhang, Bao-fang Case report: A rare case of pyruvate kinase deficiency and Crigler-Najjar syndrome type II with a novel pathogenic variant of PKLR and UGT1A1 mutation |
title | Case report: A rare case of pyruvate kinase deficiency and Crigler-Najjar syndrome type II with a novel pathogenic variant of PKLR and UGT1A1 mutation |
title_full | Case report: A rare case of pyruvate kinase deficiency and Crigler-Najjar syndrome type II with a novel pathogenic variant of PKLR and UGT1A1 mutation |
title_fullStr | Case report: A rare case of pyruvate kinase deficiency and Crigler-Najjar syndrome type II with a novel pathogenic variant of PKLR and UGT1A1 mutation |
title_full_unstemmed | Case report: A rare case of pyruvate kinase deficiency and Crigler-Najjar syndrome type II with a novel pathogenic variant of PKLR and UGT1A1 mutation |
title_short | Case report: A rare case of pyruvate kinase deficiency and Crigler-Najjar syndrome type II with a novel pathogenic variant of PKLR and UGT1A1 mutation |
title_sort | case report: a rare case of pyruvate kinase deficiency and crigler-najjar syndrome type ii with a novel pathogenic variant of pklr and ugt1a1 mutation |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10475990/ https://www.ncbi.nlm.nih.gov/pubmed/37671043 http://dx.doi.org/10.3389/fgene.2023.1229271 |
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