Clinical and Genetic Profile of Pediatric and Adult Wilson's Disease in India

Abstract

Background and aims: Wilson's disease (WD) is a disorder of copper metabolism caused by a mutation in the ATP7B gene. We aimed to comprehensively evaluate the clinical and genetic profiles of patients with WD.

Methods: This was a single-center retrospective study conducted at AIG Hospitals, Hyderabad, India. Patients diagnosed and treated for WD both in outpatient and inpatient settings from June 2020 to April 2024 were included.

Results: A total of 156 patients (women being 33.3%) with a median age of 19 years (2-57) were included from June 2020 to April 2024. Forty eight percent (n = 75) patients were of pediatric age <19 years. Clinical presentation with liver disease in the pediatric population included 26.7% with acute liver failure and 20% as acute-on-chronic liver failure compared to 30.9% with decompensated cirrhosis in the adults. On Kaplan-Meier analysis, in the pediatric group, the transplant-free survival was 72% (95% confidence interval [CI], 60.4-81.8) compared to 87.7% (95% CI, 78.5-93.9) in the adult group (P = .01) after a median duration of follow-up of 1.33 years (range, 0.01-24). Thirteen percent of patients underwent living donor liver transplantation, 0.7% (n = 1) patients developed cholangiocarcinoma, and 0.7% (n = 1) underwent transjugular intrahepatic portosystemic shunt. Seventy percent of patients underwent genetic evaluation for ATP7B mutations and 54.1% (59 of 109) were homozygous or compound heterozygous for a combination of either pathogenic variant and/or variants of uncertain significance. The most common pathogenic ATP7B variants were p.Gly977Glu, p.Cys271Ter, and p.Asn1186Ser.

Conclusion: Pediatric patients with WD present more often with an acute illness and have lower transplant-free survival compared to adults, with ATP7B mutations identified in over half of those tested, highlighting the need for early genetic evaluation and tailored management.

Keywords: ATP7B Gene; Acute Liver Failure; Acute-on-Chronic Liver Failure; Cirrhosis; Leipzig Score; Liver Transplantation.

Graphical abstract

Figure 1

Kaplan–Meier analysis of TFS.

Figure 2

Genetic variants noted in the patients with WD. A total of 109 samples were recruited for the study. Based on the existing classification of variants (ClinVar database), 23 (21.10%) of the patients were identified with 2 pathogenic variants, 26 (23.85%) with 1 pathogenic variant and 60 (55.05%) with no pathogenic variant. Of the 26 patients with 1 pathogenic variant, in 18 patients, additional VUS/conflicting variants were identified in addition. In 60 patients, where no pathogenic variant was identified, 29 patients had other VUS/conflicting variants, of which 18 patients had homozygous/compound heterozygous variants. The total patients, therefore, with pathogenic/VUS/conflicting variants with homozygous/compound heterozygous genotypes is 59 (54.13%). Of the 26 patients with one pathogenic variant, 8 patients (30.76%) had no other VUS/conflicting variants. Likewise, in the no pathogenic variant group (n = 60), 29 patients had other VUS/conflicting variants, of which 11 had only one variant. The total patients therefore with only 1 variant is 19 (17.43%). The number of patients with no variants is 31 (28.44%). The background color of the numbers in the footnote match the color of the arrows in the figure.

Figure 3

Location of genetic variants on the ATP7B gene.