Pitfall in metabolic screening in a patient with fatal peroxisomal beta-oxidation defect.

Abstract

We present a rare case of peroxisomal acyl-CoA oxidase deficiency that was not detected by the common metabolic screening program for peroxisomal disorders. The patient presented with a typical MRI pattern showing pachygyria, perisylvian polymicrogyria, cerebral and cerebellar white matter abnormalities, and facial dysmorphia, progressive psychomotor retardation, deafness, retinopathy, peripheral neuropathy, and infantile seizures strongly indicative for a peroxisomal disorder. Yet, repetitive measurements of very long-chain fatty acids (VLCFAs) and phytanic acid in serum and plasma as well as plasmalogens in erythrocytes revealed normal values apparently excluding a peroxisomal defect (methods of measurement published by Moser and co-workers in 1980 [4 ] and 1981 [2 ]). Subsequent biochemical investigation in cultured skin fibroblasts of the patient, however, revealed elevated concentrations of VLCFAs, deficient oxidation of C26:0, but normal oxidation of both phytanic acid and pristanic acid and normal DE NOVO plasmalogen synthesis, indicative for a defect in the peroxisomal beta-oxidation system. Enzymatic studies in these fibroblasts pointed to peroxisomal acyl-CoA oxidase deficiency and subsequent molecular analyses revealed a homozygous acceptor splice site mutation IVS3-1G>A in the ACOX1 gene (MIM *609751).

• Authors: H Rosewich, H R Waterham, R J A Wanders, S Ferdinandusse, M Henneke, D Hunneman, J Gärtner
• Journal: Neuropediatrics (Neuropediatrics) Vol. 37 Issue 2 Pg. 95-8 (Apr 2006) ISSN: 0174-304X [Print] Germany
• PMID: 16773508 (Publication Type: Case Reports, Journal Article)

Chemical References

• Fatty Acids
• Acyl-CoA Oxidase

Topics

• Acyl-CoA Oxidase (deficiency, genetics)
• Fatty Acids (metabolism)
• Humans
• Infant
• Male
• Peroxisomal Disorders (diagnosis, genetics, metabolism)