Neonatal adrenoleukodystrophy

Neonatal adrenoleukodystrophy (NALD) is a rare inherited peroxisomal disorder belonging to the Zellweger spectrum disorders (also known as peroxisome biogenesis disorders). It represents an intermediate form on this spectrum, less severe than Zellweger syndrome but more severe than infantile Refsum disease. NALD is caused by mutations in genes involved in peroxisome biogenesis, most commonly PEX1, PEX10, PEX13, and PEX26, among others. These mutations lead to defective peroxisome formation and function, resulting in the accumulation of very long-chain fatty acids (VLCFAs) and other metabolites in tissues throughout the body. The disease primarily affects the brain and nervous system, the adrenal glands, and the liver. Key clinical features include hypotonia (low muscle tone) presenting at birth or in early infancy, seizures, progressive white matter disease (leukodystrophy), sensorineural hearing loss, visual impairment including retinal dystrophy, hepatomegaly with liver dysfunction, and adrenal insufficiency. Affected infants typically show developmental delay and intellectual disability, with progressive neurological deterioration over time. Mild facial dysmorphism may also be present, though less pronounced than in classic Zellweger syndrome. There is currently no cure for neonatal adrenoleukodystrophy. Treatment is supportive and symptomatic, focusing on management of seizures with anticonvulsant medications, adrenal hormone replacement therapy for adrenal insufficiency, nutritional support, physical and occupational therapy, and management of hearing and vision impairments. Dietary supplementation with docosahexaenoic acid (DHA) has been explored but has not demonstrated clear clinical benefit. Prognosis varies but is generally poor, with many affected individuals surviving into childhood, though some may live into their teens or beyond depending on disease severity.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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