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G.V. Volynets

Veltishchev Research Clinical Institute of Pediatrics and Pediatric Surgery — Pirogov Russian National Research Medical University;
Pirogov Russian National Research Medical University

T.A. Skvortsova

Veltishchev Research Clinical Institute of Pediatrics and Pediatric Surgery — Pirogov Russian National Research Medical University;
Pirogov Russian National Research Medical University;
Morozovskaya Children’s City Clinical Hospital

A.V. Nikitin

Veltishchev Research Clinical Institute of Pediatrics and Pediatric Surgery — Pirogov Russian National Research Medical University;
Pirogov Russian National Research Medical University;
Morozovskaya Children’s City Clinical Hospital

Journal: Russian Journal of Evidence-Based Gastroenterology. 2025;14(1): 118–129

Two cases of Zellweger spectrum disorder with PEX26 mutations in twins

Authors:

G.V. Volynets, T.A. Skvortsova, A.V. Nikitin

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DOI: 10.17116/dokgastro202514011118

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Volynets GV, Skvortsova TA, Nikitin AV. Two cases of Zellweger spectrum disorder with PEX26 mutations in twins. Russian Journal of Evidence-Based Gastroenterology. 2025;14(1):118‑129. (In Russ., In Engl.).
https://doi.org/10.17116/dokgastro202514011118

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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.

Keywords:

Zellweger spectrum disorder
peroxisomal diseases
PEX26 mutation
neonatal adrenoleukodystrophy
peroxins

Authors:

G.V. Volynets

Veltishchev Research Clinical Institute of Pediatrics and Pediatric Surgery — Pirogov Russian National Research Medical University;
Pirogov Russian National Research Medical University

T.A. Skvortsova

Veltishchev Research Clinical Institute of Pediatrics and Pediatric Surgery — Pirogov Russian National Research Medical University;
Pirogov Russian National Research Medical University;
Morozovskaya Children’s City Clinical Hospital

A.V. Nikitin

Veltishchev Research Clinical Institute of Pediatrics and Pediatric Surgery — Pirogov Russian National Research Medical University;
Pirogov Russian National Research Medical University;
Morozovskaya Children’s City Clinical Hospital

Received:

25.12.2024

Accepted:

21.01.2025

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