Zellweger spectrum disorder presenting with opsoclonus-myoclonus-ataxia syndrome: a case report on immunotherapy.

Introduction: Zellweger spectrum disorder (ZSD) refers to a group of autosomal recessive genetic disorders that affect multiple organ systems and are predominantly caused by pathogenic variants in PEX genes. ZSD present a wide clinical spectrum, ranging from the most severe form, Zellweger syndrome, to the mildest form, Heimler syndrome.

Case Report: A 14-month-old male patient was brought to our clinic with recent-onset ocular tremors and unsteady gait. Based on the preliminary suspicion of an infection-related autoimmune disease, the patient received intravenous immunoglobulin (IVIG) and pulse steroid therapy. Although initial clinical improvement was observed in opsoclonus and ataxia, ocular symptoms later recurred. Peroxisomal profile revealed elevated plasma levels of phytanic acid, pristanic acid, and very long-chain fatty acids (C26), raising suspicion for ZSD. Consequently, dietary restrictions for very long-chain fatty acids, phytanic acid, and pristanic acid, along with vitamin supplementation (A, D, E, and K), were initiated. Molecular genetic testing identified a homozygous c.2528G > A, p.(Gly843Asp) pathogenic variant in the PEX1 gene, confirming the diagnosis.

Conclusion: Zellweger spectrum disorder presents with a wide range of clinical manifestations. While no effective treatment currently exists, a diet restricted in very long-chain and branched-chain fatty acids, supplementation with vitamins A, D, E, and K, and bile acid therapy are commonly used. In our patient, IVIG and pulse steroid therapy were administered due to a preliminary suspicion of an autoimmune process, resulting in a short-term partial clinical response. To our knowledge, the use of immunotherapy in ZSD has not been previously reported in the literature.