Two cases of Zellweger spectrum disorder with PEX26 mutations in twins

Zellweger spectrum disorders (ZSD) are a group of rare autosomal recessive diseases caused by peroxisome biogenesis defects. They are characterized by multisystem involvement, including neurological impairments, liver and kidney dysfunction, and developmental anomalies. The disease is driven by mutations in PEX genes, which regulate peroxisome formation and function. This article presents two clinical cases of ZSD in twins with a homozygous PEX26 mutation, a rare phenomenon that expands the known genotype-phenotype correlations. Clinical case. Twin boys were followed by a pediatrician from 11 months of age. Both exhibited hypotonia, progressive motor impairment, vision loss, and delayed psychomotor development. One twin had a more severe course with early liver involvement, coagulopathy, and portal hypertension. Genetic analysis identified a previously unreported homozygous c.T347A:p.L116Q mutation in exon 3 of the PEX26 gene (NM_017929), likely associated with neonatal adrenoleukodystrophy, a relatively mild ZSD variant. Conclusion. These cases contribute to the understanding of PEX26-related phenotypic manifestations and highlights the heterogeneity of ZSD. The findings suggest a possible link between residual peroxin activity and a milder disease course. Early diagnosis and multidisciplinary management are crucial for improving prognosis and quality of life in children with Zellweger spectrum disorders.