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

Frontiers in Genetics

Genetics

Long Wu¹  Bao-fang Zhang²  Huan Wu²  Quan Zhang² 

[1] Department of Anus and Intestinal Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China;Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China;

关键词: pyruvate kinase deficiency;    Crigler-Najjar syndrome;    next-generation sequencing;    PKLR;    UGT1A1;    case report;   

DOI  :  10.3389/fgene.2023.1229271

 received in 2023-05-26, accepted in 2023-07-05,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

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Copyright © 2023 Wu, Wu, Zhang and Zhang.