Monoamine oxidase (
MAO) exists as two
isoenzymes and plays a central role in the metabolism of monoamine
neurotransmitters. In this study we compared the neurochemical phenotypes of previously described subjects with genetically determined selective lack of
MAO-A or a lack of both
MAO-A and
MAO-B with those of two subjects with a previously described X chromosome microdeletion in whom we now demonstrate selective
MAO-B deficiency. Mapping of the distal deletion breakpoint demonstrates its location in intron 5 of the
MAO-B gene, with the deletion extending proximally into the
Norrie disease gene. In contrast to the borderline
mental retardation and abnormal behavioral phenotype in subjects with selective
MAO-A deficiency and the severe
mental retardation in patients with combined
MAO-A/
MAO-B deficiency and
Norrie disease, the
MAO-B-deficient subjects exhibit neither abnormal behavior nor
mental retardation. Distinct neurochemical profiles characterize the three groups of
MAO-deficient patients. In
MAO-A-deficient subjects, there is a marked decrease in deaminated
catecholamine metabolites and a concomitant marked elevation of O-methylated
amine metabolites. These neurochemical changes are only slightly exaggerated in patients with combined lack of
MAO-A and
MAO-B. In contrast, the only biochemical abnormalities detected in subjects with the
MAO-B gene deletion are a complete absence of platelet
MAO-B activity and an increased urinary excretion of phenylethylamine. The differences in neurochemical profiles indicate that, under normal conditions,
MAO-A is considerably more important than
MAO-B in the metabolism of
biogenic amines,
a factor likely to contribute to the different clinical phenotypes.