Plasma amine oxidase activities in Norrie disease patients with an X-chromosomal deletion affecting monoamine oxidase

Abstract

Two individuals with an X-chromosomal deletion were recently found to lack the genes encoding monoamine oxidase type A (MAO-A) and MAO-B. This abnormality was associated with almost total (90%) reductions in the oxidatively deaminated urinary metabolites of the MAO-A substrate, norepinephrine, and with marked (100-fold) increases in an MAO-B substrate, phenylethylamine, confirming systemic functional consequences of the genetic enzyme deficiency. However, urinary concentrations of the deaminated metabolites of dopamine and serotonin (5-HT) were essentially normal. To investigate other deaminating systems besides MAO-A and MAO-B that might produce these metabolites of dopamine and 5-HT, we examined plasma amine oxidase (AO) activity in these two patients and two additional patients with the same X-chromosomal deletion. Normal plasma AO activity was found in all four Norrie disease-deletion patients, in four patients with classic Norrie disease without a chromosomal deletion, and in family members of patients from both groups. Marked plasma amine metabolite abnormalities and essentially absent platelet MAO-B activity were found in all four Norrie disease-deletion patients, but in none of the other subjects in the two comparison groups. These results indicate that plasma AO is encoded by gene(s) independent of those for MAO-A and MAO-B, and raise the possibility that plasma AO, and perhaps the closely related tissue AO, benzylamine oxidase, as well as other atypical AOs or MAOs encoded independently from MAO-A and MAO-B may contribute to the oxidative deamination of dopamine and 5-HT in humans.

Monoamine oxidase‐A: pharmacodynamics in humans of moclobemide, a reversible and selective inhibitor.

“…This suggests that serotonin can be metabolized to 5HIAA by enzymes other than MAO-A. Further studies of these patients have shown that they possess normal plasma amine oxidase activity [23].…”

Association analysis of the functional monoamine oxidase a gene promoter polymorphism in psychiatric disorders

“…Similar neurochemical and behavioral changes are found in male MAOA knockout mice [Cases et al, 1995]. Patients with sub-microscopic deletions of the MAO region show, in addition to the main symptoms of Norrie disease, profound mental retardation, often with psychotic features and sleep disturbance [Sims et al, 1989] as well as changes in amine metabolism [Murphy et al, 1990[Murphy et al, , 1991. The in¯uence of allelic variants on the metabolism of several key neurotransmitters indicates the MAOA gene as an interesting candidate in the genetic dissection of syndromal dimensions associated with psychiatric disorders and psychopharmacological drug response.…”

Specific genetic deficiencies of the A and B isoenzymes of monoamine oxidase are characterized by distinct neurochemical and clinical phenotypes.

“…Hybridizing fragments were assigned to specific MAO-B exons based on published data (22). The detailed description of the genetic defects in the MAO-A-and MAO-AB-deficient subjects have been reported previously (5)(6)(7)(8)(10)(11)(12).…”

“…In addition to the blindness, hearing loss, and variable mental retardation that characterize Norrie disease (10), patients with the additional deletion of both MAO genes show profound mental retardation, autistic-like behavior, atonic seizures, altered peripheral autonomic function, and profound alterations in biogenic amine metabolism (5,6,8). More recently, selective loss of MAO-A activity due to a point mutation in exon 8 of the MAO-A gene was described in a Dutch kindred (11,12).…”