Pitfall in metabolic screening in a patient with fatal peroxisomal beta-oxidation defect.
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).
Rosewich
H
H
Department of Pediatrics and Pediatric Neurology, Georg August University Goettingen, Robert-Koch-Strasse 40, 37075 Goettingen, Germany. hendrik.rosewich@med.uni-goettingen.de
Waterham
H R
HR
Wanders
R J A
RJ
Ferdinandusse
S
S
Henneke
M
M
Hunneman
D
D
Gärtner
J
J
D042962:Acyl-CoA Oxidase / Q000172:deficiency* / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008297:Male; D018901:Peroxisomal Disorders / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*
D005227:Fatty Acids; D042962:Acyl-CoA Oxidase