Characteristic acylcarnitine profiles in inherited defects of peroxisome biogenesis: a novel tool for screening diagnosis using tandem mass spectrometry.
Patients with inherited defects of peroxisomal metabolism, a class of diseases with marked clinical and genetic heterogeneity, show a characteristic phenotype in most cases with severe neurologic impairment, craniofacial abnormalities, and hepatic and kidney dysfunction. For the differential diagnosis of clinically suspected cases, a complex biochemical and genetic approach is required. Analysis of plasma very-long-chain fatty acids is a reliable screening method to detect most but not all peroxisomal disorders. To study the potential presence of abnormal acylcarnitine species in plasma and blood, we screened by tandem mass spectrometry a series of patients affected by a peroxisome biogenesis disorder (PBD) and compared the results with those obtained in patients with isolated peroxisomal defects (e.g. D-bifunctional protein deficiency, X-linked adrenoleukodystrophy) and mitochondrial long-chain fatty acid oxidation defects. The most relevant finding observed in plasma of patients with PBD was a significant increase of long-chain dicarboxylic C16- and C18-carnitine, i.e. hexadecanedioyl- and octadecanedioyl-carnitine, with high dicarboxylycarnitine/monocarboxylylcarnitine ratio. Elevation of very long-chain acylcarnitines C24- and C26-, i.e. lignoceroyl- and cerotoyl-carnitine, was detected in some PBDs and in D-bifunctional protein deficiency. Similar abnormalities were also found in neonatal screening blood spots. Detection of these compounds alone, in the absence of other shorter-chain acylcarnitines, is highly specific and characteristic of PBD, as confirmed by the differing profiles observed in patients with adrenoleukodystrophy and mitochondrial long-chain fatty acid oxidation defects. Our study adds a novel method to the diagnosis of PBD, which may also be of benefit for future neonatal mass screening programs based on acylcarnitine profiling.
Rizzo
Cristiano
C
Division of Metabolism, Bambino Gesù Research Institute, 00165 Rome, Italy.
Boenzi
Sara
S
Wanders
Ronald J A
RJ
Duran
Marinus
M
Caruso
Ubaldo
U
Dionisi-Vici
Carlo
C
D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D018901:Peroxisomal Disorders / Q000175:diagnosis*; D020675:Peroxisomes / Q000378:metabolism*
C116917:acylcarnitine; D002331:Carnitine