ADRENOLEUKODYSTROPHY (ALD) is an X-linked genetic disorder characterized by severe demyelination in the brain and by the presence of the unusual and perhaps unique crystalline material in the brain, adrenal and testis of patients (SCHAUMBURG et a/., 1972). Most cases in the literature reported as Schilder's disease or sudanophilic leukodystrophy with or without adrenal involvement appear to belong to this disease entity (SCHAUMBURG et a/., 1975). While the fundamental genetic defect of the disease has not been clarified, our recent study indicated presence of extremely long-chain fatty acids in cholesterol esters of the brain and adrenal, in brain gangliosides, and to much lesser degrees, in brain galactosylceramide (IGAR-ASHI et a/., 1976).

An abnormal ganglioside pattern was reported earlier in white matter of an ALD patient with increased proportions of two molecular species with thin-layer chromatographic mobilities similar to GD2-and GD,-gangliosides, respectively (SUZUKI et al., 1970). The fatty acid abnormality of ganglioside was most conspicuous in the patient with such an abnormal pattern. In such an instance, almost half of total fatty acids were longer than Czl. This is a very unusual abnormality because normal brain ganglioside contains approx 90% stearic acid and practically none longer than Cz1. These findings cast doubt on the tentative identification of the abnormally-increased gangliosides, because TLC mobility of ganglioside may be substantially altered according to the fatty acid composition. The spots identified as GU2 and GD3 might possibly be merely GDlh and G,, l, containing the very long-chain fatty acids. Other questions are also raised. Are the abnormal long-chain fatty acids only in some gangliosides, or are they evenly distributed? Are they amide-linked as in normal gangliosides or are they possibly ester-linked to any of the carbohydrate moieties? Such compounds will surely give faster TLC mobility than the parent compounds with only one amide-linked fatty acids. Analogous galactosylceramide with an additional fatty acid ester-linked to C3 or C, of galactose is known (NORTON & BROTZ, 1963; TAMAI et a/., 1967; KSHIMOTO et aE., 1968; KLENK & LOHR, 1967). Since the answers to the above questions would have important bearing in interpretation of the fatty acid abnormality with respect to the metabolic defect in ALD, we have examined the brain gangliosides in ALD further.