Chapter 91 - Monoamine Oxidase Deficiency

Abstract

Monoamine oxidase A (MAO-A) and B (MAO-B) catalyze the oxidative deamination of biogenic monoamines. The genes encoding MAO-A and MAO-B are located close to the gene for Norrie disease (ND). Exclusive deletion of the ND gene results in X-linked congenital blindness, and in 30–50% patients, to progressive hearing loss and mild mental retardation. Loss of MAO-A and MAO-B activity was reflected neurochemically by severely reduced plasma and urinary concentrations of catecholamine deaminated metabolites, including dihydroxyphenylglycol (DHPG), the deaminated metabolite of norepinephrine and epinephrine. MAO-A knock-out mice demonstrated aggressive behavior, probably related to impaired metabolic degradation of 5-HT in an experiment. These mice showed significantly increased 5-HT levels in several brain areas and architectural alterations in the somatosensory cortex. Apart from different affinities for monoamine substrate, the importance of MAO-A for catecholamine metabolism likely reflects selective expression of MAO-A in catecholaminergic neurons, the cellular compartment where most catecholamine deamination takes place. Two patients have been identified with deletions of MAO-B and ND genes, but with the MAO-A gene intact.