Plasma amine oxidase activities in Norrie disease patients with an X-chromosomal deletion affecting monoamine oxidase.
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.
Murphy
D L
DL
Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD.
Sims
K B
KB
Karoum
F
F
Garrick
N A
NA
de la Chapelle
A
A
Sankila
E M
EM
Norio
R
R
Breakefield
X O
XO
D000293:Adolescent; D000328:Adult; D006631:Amine Oxidase (Copper-Containing); D001766:Blindness / Q000201:enzymology / Q000235:genetics*; D002872:Chromosome Deletion; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008995:Monoamine Oxidase / Q000172:deficiency* / Q000235:genetics; D009638:Norepinephrine / Q000378:metabolism; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000097:blood*; D010627:Phenethylamines / Q000378:metabolism; D012160:Retina / Q000002:abnormalities*; D012701:Serotonin / Q000378:metabolism*; D012729:Sex Chromosome Aberrations / Q000201:enzymology*; D014960:X Chromosome
D010627:Phenethylamines; D012701:Serotonin; D006631:Amine Oxidase (Copper-Containing); D008995:Monoamine Oxidase; D000587:Oxidoreductases Acting on CH-NH Group Donors; D004298:Dopamine; D009638:Norepinephrine