Peroxisomal disorders are inherited diseases affecting the formation or function of peroxisomes, cellular organelles involved in very-long-chain fatty-acid metabolism, plasmalogen synthesis and other essential pathways. Epilepsy is especially important in severe Zellweger-spectrum and related disorders.
Zellweger spectrum disorder
Zellweger spectrum disorder (ZSD) is caused by biallelic pathogenic variants in one of several PEX genes required for peroxisome biogenesis.
The spectrum ranges from severe neonatal disease to milder childhood or adult phenotypes.
Severe neonatal ZSD
Severely affected newborns can have profound hypotonia, poor feeding, liver dysfunction, craniofacial features, neuronal migration abnormalities and seizures.
Renal cysts and skeletal abnormalities may also occur.
Why seizures occur
Seizures may result from cortical malformations, abnormal neuronal migration and widespread biochemical dysfunction.
The epilepsy therefore forms part of a multisystem disease.
Milder Zellweger-spectrum disease
People with milder ZSD may present later with hearing loss, retinal disease, leukodystrophy, ataxia, neuropathy, adrenal dysfunction or liver disease.
Epilepsy can occur but may not dominate the phenotype.
Other peroxisomal conditions
Peroxisomal disease also includes rhizomelic chondrodysplasia punctata and single-enzyme disorders such as X-linked adrenoleukodystrophy.
The seizure risk and neurological phenotype differ substantially between disorders.
Diagnosis
Testing can include very-long-chain fatty acids, plasmalogens, bile-acid intermediates and other specialised biochemical markers.
Molecular testing identifies the responsible gene.
MRI
Severe ZSD can show neuronal migration abnormalities and white-matter disease.
Later-onset peroxisomal disorders can show progressive leukodystrophy.
Treatment
There is no single treatment for all peroxisomal disorders.
Seizures are treated according to type while liver, nutritional, adrenal, visual, hearing and respiratory problems are managed simultaneously.
Supportive epilepsy care
Medication selection should consider liver dysfunction and feeding difficulties.
Rescue plans may be necessary in people with prolonged seizures.
Adrenal insufficiency
Some peroxisomal diseases, particularly X-linked adrenoleukodystrophy and some ZSD phenotypes, can involve adrenal insufficiency.
Adrenal crisis can itself cause altered consciousness and systemic deterioration and must be distinguished from seizures.
Hearing and vision
Sensorineural hearing loss and retinal disease are common in milder ZSD.
Communication and developmental assessment should account for these sensory impairments.
Genetics
ZSD is autosomal recessive.
More than a dozen PEX genes can cause the condition, with PEX1 among the most common.
Worldwide access
Diagnosis requires specialised biochemical testing that may not be available in many health systems.
Genomic sequencing can identify a PEX-gene diagnosis but biochemical confirmation remains important for characterising peroxisomal function.
The central point
Epilepsy in peroxisomal disease is usually one feature of a multisystem metabolic disorder involving brain development, white matter, liver, vision, hearing and sometimes adrenal function.
Related reading
Sources
Medical note: suspected peroxisomal disease requires specialist metabolic and genetic assessment because neurological symptoms may coexist with serious systemic complications.
Evidence checked: September 2026.