The objective of this study is to evaluate 200 chronically ill psychiatric patients for the presence of a leukodystrophy or the leukodystrophic carrier state and to relate the metabolic defect in these patients with neurocognitive impairment. The presence of metachromatic leukodystrophy (MLD) is indicated by a decrease in Aryl sufatase A (ASA) activity. The presence of globoid cell leukodystrophy is indicated by a deficiency in galactosyl ceramide B-galacto-sidase activity and the presence of adrenoleukodystrophy is indicated by the accumulation of a very long chain fatty acids (VLCFA) in body tissues. The specific enzymatic defect causing accumulation of long chain fatty acids is unknown. There is strong evidence, however, of the loss of capacity to degrade very long chain fatty acid caused by a single defective peroxisomal enzyme. Inherited metabolic disorders such as metachromatic leukodystrophy (MLD) are known to occur with greater frequency in psychiatric patients than in the general population. Because the frequency of occurrence is not well appreciated, these diseases which involve characteristic brain pathology are often misdiagnosed as unrelated psychiatric disorder. Carriers (heterozygotes) for these metabolic disorders have been regarded as clinically unaffected. However, the less than 50% of normal enzyme activity expected in the carriers of the leukodystrophies may not be enough for normal functioning. Moreover, different alleles at the same locus can result in very low enzyme activity in carriers and in some of their relatives. Individuals with very low levels of enzyme activities may be more susceptible to dysfunction. Also, detection of the carrier condition is important for genetic counseling.
| Shah, S N; Johnson, R C; Minn, K et al. (1995) Arylsulfatase A and beta-galactosidase activities in leukocytes and lymphocytes from normal and psychiatric subjects. Effects of blood-processing delay and interleukin-2 stimulation. Mol Chem Neuropathol 24:43-52 |
