Molecular species profiles of plasma ceramides in different clinical types of X-linked adrenoleukodystrophy.

ABSTRACT

X-linked adrenoleukodystrophy (X-ALD) is a genetic disorder associated with peroxisomal dysfunction. Patients with this rare disease accumulate very long-chain fatty acids (VLCFAs) in their bodies because of impairment of peroxisomal VLCFA ?-oxidation. Several clinical types of X-ALD, ranging from mild (axonopathy in the spinal cord) to severe (cerebral demyelination), are known. However, the molecular basis for this phenotypic variability remains largely unknown. In this study, we determined plasma ceramide (CER) profile using liquid chromatography-tandem mass spectrometry. We characterized the molecular species profile of CER in the plasma of patients with mild (adrenomyeloneuropathy;AMN) and severe (cerebral) X-ALD. Eleven X-ALD patients (five cerebral, five AMN, and one carrier) and 10 healthy volunteers participated in this study. Elevation of C260 CER was found to be a common feature regardless of the clinical types. The level of C261 CER was significantly higher in AMN but not in cerebral type, than that in healthy controls. The C261 CER level in the cerebral type was significantly lower than that in the AMN type. These results suggest that a high level of C260 CER, along with a control level of C261 CER, is a characteristic feature of the cerebral type X-ALD. J. Med. Invest. 70 403-410, August, 2023.