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Introduction <p>Peroxisome biogenesis disorders (PBDs) are rare autosomal recessive neurodegenerative diseases caused by variants in Peroxin (<i>PEX)</i> genes, leading to defective peroxisome assembly and multisystem dysfunction. The <i>PEX12</i> variant NM_000286.3: c.1047_1049del (NP_000277.1: p.Gln349del) has been described almost exclusively in Egyptian patients, suggesting a founder effect. We present the first Egyptian case with this variant showing bilateral optic atrophy, expanding the known clinical phenotype of <i>PEX12</i>-related PBD.</p> Case presentation <p>A six-year-old Egyptian boy, born to first-cousin parents, presented with early hypotonia, developmental regression, visual inattention, and sensorineural hearing loss. Early milestones were initially normal, followed by progressive motor and cognitive decline beginning at age three. Ophthalmologic examination revealed bilateral optic atrophy, and audiologic testing confirmed profound sensorineural hearing loss. Brain Magnetic Resonance Imaging (MRI) showed bilateral periventricular and cerebellar white matter hyperintensities, with restricted diffusion in the involved areas and corpus callosum involvement. Laboratory studies were unremarkable, but trio whole-exome sequencing identified a homozygous <i>PEX12</i> deletion (c.1047_1049del), confirming a diagnosis within the Zellweger spectrum of peroxisome biogenesis disorders. The patient was managed with supportive multidisciplinary care, including levetiracetam for seizure control, physiotherapy, nutritional support, and regular follow-up. At one-year follow-up, seizures were controlled, but severe neurological disability persisted.</p> Conclusion <p>This case highlights a rare <i>PEX12</i>-related peroxisome biogenesis disorder with optic atrophy—an unreported feature of this variant—broadening its phenotypic spectrum. It underscores the diagnostic value of whole-exome sequencing when biochemical tests are inconclusive and emphasizes the need for increased awareness of founder variants in populations with high consanguinity to enable earlier diagnosis, counseling, and targeted screening.</p>

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Early hypotonia and visual regression as presenting features of peroxisome biogenesis disorder: an Egyptian case report

  • 期刊论文

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  • 发表日期：

    2026年5月18日

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  • Abdelrahim A. Sadek,
  • Mohammed A. Aladawy,
  • Khaled Hassan,
  • Tarek M. M. Mansour,
  • Mohamed Naser,
  • Mohamed M. Elmoursy,
  • Sohieb Hedewy,
  • Ahmed Hagag,
  • Kawashty Ragab Mohamed,
  • Elsayed Abdelkreem

摘要

Introduction

Peroxisome biogenesis disorders (PBDs) are rare autosomal recessive neurodegenerative diseases caused by variants in Peroxin (PEX) genes, leading to defective peroxisome assembly and multisystem dysfunction. The PEX12 variant NM_000286.3: c.1047_1049del (NP_000277.1: p.Gln349del) has been described almost exclusively in Egyptian patients, suggesting a founder effect. We present the first Egyptian case with this variant showing bilateral optic atrophy, expanding the known clinical phenotype of PEX12-related PBD.

Case presentation

A six-year-old Egyptian boy, born to first-cousin parents, presented with early hypotonia, developmental regression, visual inattention, and sensorineural hearing loss. Early milestones were initially normal, followed by progressive motor and cognitive decline beginning at age three. Ophthalmologic examination revealed bilateral optic atrophy, and audiologic testing confirmed profound sensorineural hearing loss. Brain Magnetic Resonance Imaging (MRI) showed bilateral periventricular and cerebellar white matter hyperintensities, with restricted diffusion in the involved areas and corpus callosum involvement. Laboratory studies were unremarkable, but trio whole-exome sequencing identified a homozygous PEX12 deletion (c.1047_1049del), confirming a diagnosis within the Zellweger spectrum of peroxisome biogenesis disorders. The patient was managed with supportive multidisciplinary care, including levetiracetam for seizure control, physiotherapy, nutritional support, and regular follow-up. At one-year follow-up, seizures were controlled, but severe neurological disability persisted.

Conclusion

This case highlights a rare PEX12-related peroxisome biogenesis disorder with optic atrophy—an unreported feature of this variant—broadening its phenotypic spectrum. It underscores the diagnostic value of whole-exome sequencing when biochemical tests are inconclusive and emphasizes the need for increased awareness of founder variants in populations with high consanguinity to enable earlier diagnosis, counseling, and targeted screening.