Spectrum of Pathogenic Variants in ATP7B Gene Causing Wilson Disease in Mexican Patients.

BACKGROUND

Wilson disease (WD) is a multisystemic disorder caused by a disturbance in copper homeostasis due to pathogenic biallelic variants in the ATP7B gene.

AIM: To identify the pathogenic variants in the ATP7B gene in Mexican individuals with WD and describe their phenotypic presentation.

METHODS

We included 19 individuals from 11 unrelated families with molecularly confirmed WD.

RESULTS

52.6% of the WD patients were male, and three were asymptomatic at diagnosis. The median age at presentation was 19 years. Of the symptomatic individuals, 84.2% had hepatic manifestations, 62.5% had neurological symptoms, 25.0% had psychiatric manifestations, and 90.9% had Kayser-Fleischer rings. The phenotypic distribution was as follows: combined (52.6%), acute liver failure (26.3%), chronic liver disease (5.3%), and asymptomatic (15.8%). Modified Leipzig scores ranged from 8 to 16. Five patients underwent liver transplantation, and eight patients were treated with copper chelators. Eight different pathogenic variants were identified, including the recurrent c.3207C>A and c.3809A>G, as described in other series.

CONCLUSIONS

We present the first and largest case series of Mexican patients with WD confirmed by molecular testing. All patients exhibited hepatic manifestations. The most frequent phenotypes were combined (52.6%) and acute liver failure (26.3%). A statistically significant difference in the frequency of asymptomatic patients was observed between the homozygous c.3207C>A genotype group and the group with other genotypes (p = 0.036). The modified Leipzig score is a valuable diagnostic tool for WD.