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Myopathy in an infant with a fatal peroxisomal disorder
1Department of Pediatrics, University of California San Diego, La Jolla 92093.
Insights
Neonatal adrenoleukodystrophy caused severe hypotonia and seizures in an infant. The study found impaired fatty acid oxidation and reduced plasmalogen synthesis, indicating mitochondrial and peroxisomal dysfunction.
Area of Science:
- Biochemistry
- Cell Biology
- Pediatric Neurology
Background:
- Neonatal adrenoleukodystrophy (NALD) is a severe peroxisomal biogenesis disorder.
- It presents with neurological and adrenal dysfunction.
- Early diagnosis and understanding of pathogenic mechanisms are crucial.
Observation:
- An infant diagnosed with NALD exhibited profound hypotonia and continuous convulsions by four months of age.
- Histopathological examination revealed myopathy and mitochondrial inclusions.
- Clinical deterioration led to the infant's death.
Findings:
- Elevated very long-chain fatty acids (VLCFAs) in blood and fibroblasts confirmed NALD.
- Defective oxidation of fatty acids and increased urinary pipecolic acid were observed.
- Reduced activity of dihydroxyacetone phosphate acyltransferase indicated impaired plasmalogen synthesis.
Implications:
- This case highlights the severe neurological impact of NALD.
- It underscores the importance of identifying biochemical markers like VLCFAs and pipecolic acid.
- Understanding peroxisomal and mitochondrial dysfunction is key for NALD management.
Abstract:
An infant with neonatal adrenoleukodystrophy experienced extreme hypotonia and virtually continuous convulsions at four months of age and died. Light and electron microscopic examination revealed evidence of myopathy and the presence of mitochondrial inclusions. Concentrations of very long-chain fatty acids were elevated in blood and fibroblasts and the oxidation of 14C-labeled fatty acids was defective. Urinary pipecolic acid content was increased. Activity of the peroxisomal dihydroxyacetone phosphate acyltransferase, which catalyzes the first step in plasmalogen synthesis, was decreased.