Biliary atresia combined Wilson disease identified by whole exome sequencing in Vietnamese patient with severe liver failure

Abstract

Rationale: Hepatobiliary diseases such as biliary atresia (BA), Wilson disease, and progressive familial intrahepatic cholestasis are common causes of morbidity and mortality in young children. Affected patients progress rapidly to end-stage cirrhosis and require liver transplantation or die. Mutations in many genes have been identified to play an important role in the pathogenesis of hepatobiliary diseases. Patient concerns and diagnosis: In this study, we identified mutations in an 8-year-old girl who had severe liver failure. The patient was first diagnosed with BA at 2.5 months of age and has undergone Kasai surgery to connect the umbilical cord and jejunum. After that, the patient suddenly had unusual developments with symptoms of jaundice, acute liver failure with hemolysis. She was tested and diagnosed with Wilson disease. Interventions and outcomes: She was treated according to the regimen for a patient with Wilson disease but had abnormal progress leading to severe liver failure. Genetic analysis was performed by whole exome sequencing and Sanger sequencing methods. The genetic analysis revealed that the patient had a homozygous mutation (p.Gly17Glyfs77∗) in the KRT18 gene, a double heterozygous mutation (p.Ser105∗ and p.Pro992Leu) in the ATP7B gene, and a homozygous variant (p.Val444Ala) in the ABCB11 gene. In silico prediction of mutations indicated that these mutations are the cause of the severe liver failure in the patient. Lesson: This is a rare clinical case of a BA patient combined with Wilson disease. Our results suggested that whole exome sequencing is an effective diagnostic tool and emphasizes the importance of early diagnosis and appropriate management to save lives and prevent serious complications in the patient.

Identification of novel compound ATP7B mutations in a child with rare Wilson disease: A case report

“…However, precise diagnosis is challenging and may be delayed if the patient manifests liver dysfunction for unknown reasons or presents with mild and nonspeci c or no symptoms. In such situations, molecular genetic tests, especially WES for detecting causative mutations in all the encoding genes, are powerful for early diagnosis and treatment (10). According to the Leipzig scoring for WD diagnosis (6), the patient in this study had 6 points, including 2 points for ceruloplasmin and 4 points for causative genetic mutations, indicating the importance of genetic tests in early diagnosis of WD.…”

Rare sequence variants associated with the risk of non‐syndromic biliary atresia

“…We examined the frequencies of 60 known BA‐related SNPs in the patient and control groups. These SNPs were selected based on the previous reports 5–28 . We confirmed that the identified SNPs were in Hardy–Weinberg equilibrium.…”

“…To date, candidate gene approaches, genome‐wide association studies, and whole exome sequencing (WES) detected 60 single‐nucleotide polymorphisms (SNPs) and 75 genes associated with the risk for non‐syndromic BA 5–28 . For example, WES by Gürünlüoğlu et al.…”