Specific genetic deficiencies of the A and B isoenzymes of monoamine oxidase are characterized by distinct neurochemical and clinical phenotypes.
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.
Lenders
J W
JW
Department of Medicine, Division of General Internal Medicine, St. Radboud University Hospital, Nijmegen, The Netherlands.
Eisenhofer
G
G
Abeling
N G
NG
Berger
W
W
Murphy
D L
DL
Konings
C H
CH
Wagemakers
L M
LM
Kopin
I J
IJ
Karoum
F
F
van Gennip
A H
AH
Brunner
H G
HG
D000328:Adult; D001766:Blindness / Q000235:genetics; D001792:Blood Platelets / Q000737:chemistry; D002395:Catecholamines / Q000378:metabolism*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D008995:Monoamine Oxidase / Q000172:deficiency*; D010641:Phenotype; D017384:Sequence Deletion; D012701:Serotonin / Q000097:blood; D014960:X Chromosome
D002395:Catecholamines; D012701:Serotonin; D008995:Monoamine Oxidase