Lenders J W, Eisenhofer G, Abeling N G, Berger W, Murphy D L, Konings C H, Wagemakers L M, Kopin I J, Karoum F, van Gennip A H, Brunner H G
Department of Medicine, Division of General Internal Medicine, St. Radboud University Hospital, Nijmegen, The Netherlands.
J Clin Invest. 1996 Feb 15;97(4):1010-9. doi: 10.1172/JCI118492.
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.
单胺氧化酶（MAO）以两种同工酶的形式存在，在单胺类神经递质的代谢中起核心作用。在本研究中，我们将先前描述的、经基因测定选择性缺乏MAO - A或同时缺乏MAO - A和MAO - B的受试者的神经化学表型，与两名先前描述有X染色体微缺失的受试者（我们现在证实他们存在选择性MAO - B缺乏）的神经化学表型进行了比较。远端缺失断点的定位显示其位于MAO - B基因的内含子5中，缺失向近端延伸至诺里病基因。与选择性MAO - A缺乏的受试者的边缘智力迟钝和异常行为表型以及MAO - A/MAO - B联合缺乏和诺里病患者的严重智力迟钝不同，MAO - B缺乏的受试者既没有异常行为也没有智力迟钝。三组MAO缺乏患者具有不同的神经化学特征。在MAO - A缺乏的受试者中，脱氨基儿茶酚胺代谢产物显著减少，同时O - 甲基化胺代谢产物显著升高。这些神经化学变化在MAO - A和MAO - B联合缺乏的患者中仅略有加剧。相比之下，在MAO - B基因缺失的受试者中检测到的唯一生化异常是血小板MAO - B活性完全缺失以及苯乙胺尿排泄增加。神经化学特征的差异表明，在正常情况下，MAO - A在生物胺代谢中比MAO - B重要得多，这一因素可能导致了不同的临床表型。
