Monoamine oxidase deficiency

Douglas J Lanska MD FAAN MS MSPH (

Dr. Lanska of the University of Wisconsin School of Medicine and Public Health, the Medical College of Wisconsin, and IM Sechenov First Moscow State Medical University has no relevant financial relationships to disclose.

Originally released March 30, 1995; last updated November 21, 2019; expires November 21, 2022

This article includes discussion of monoamine oxidase deficiency, monoamine oxidase-A deficiency, MAO-A deficiency, and MAO deficiency. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.


Monoamine oxidase-A deficiency is an X-linked disorder affecting the catabolism of serotonin and the catecholamines. Main symptoms are mild intellectual disability and behavioral abnormalities consisting of excessive, sometimes violent aggression. Diagnosis may be inferred from a finding of elevated urinary concentrations of the monoamine oxidase-A substrates, normetanephrine, 3-methoxytyramine, and tyramine, in combination with reduced amounts of the monoamine oxidase products, vanillylmandelic acid, homovanillic acid, 3-methoxy-4-hydroxyphenolglycol, and 5-hydroxyindoleacetic acid. Monoamine oxidase deficiency has been found as an isolated defect affecting monoamine oxidase A and, in combination with a deletion of the Norrie disease gene, as a combined deficiency of monoamine oxidase A and B or an isolated deficiency of monoamine oxidase B. Confirmation of monoamine oxidase-A deficiency is obtained by measurement of the activity of this enzyme in dexamethasone-stimulated fibroblasts. Combined monoamine oxidase-A and B deficiency has similar biochemical consequences. Presentation is with intermittent hypotonia, stereotypic hand movements, and developmental delay.

Key points


• Monoamine oxidase deficiency is inherited as an X-linked trait.


• Monoamine oxidase exists in two distinct forms encoded by separate genes, monoamine oxidase-A and monoamine oxidase-B, and each has preferential affinities for biogenic amine and other amine substrates.


• Monoamine oxidase deficiency has been described as isolated monoamine oxidase-A deficiency, as a combined monoamine oxidase-A and B deficiency, as a combined monoamine oxidase-A and B deficiency in association with Norrie disease, and as an isolated monoamine oxidase-B deficiency in association with Norrie disease.


• Individuals with monoamine oxidase deficiency should avoid foods or drugs containing amines.

Historical note and terminology

Deficiency of monoamine oxidase has been described in association with Norrie disease (an X-linked syndrome characterized by congenital blindness, hearing loss, and variable mental retardation) (de la Chapelle et al 1985; Sims et al 1989a; Sims et al 1989b), as an isolated defect affecting only monoamine oxidase-A, and as a combined deficiency of both monoamine oxidase-A and B in the absence of Norrie disease. Five patients with X chromosome deletions including monoamine oxidase-A and monoamine oxidase-B, as well as the Norrie disease gene, had severe mental retardation, autistic-like behavior, abnormal peripheral autonomic function, and atonic seizures (Collins et al 1992; Lenders et al 1996), whereas two brothers with a complex deletion involving the Norrie disease gene and a part of the monoamine oxidase-B structural gene, but with an intact monoamine oxidase-A gene, had no psychiatric symptoms or mental retardation (Berger et al 1992; Lenders et al 1996). Norrie disease may occur without affecting either monoamine oxidase-A or -B (Liu et al 2019). Involvement of deletions of the X chromosome in areas other than the structural genes for monoamine oxidase-A gene and monoamine oxidase-B impedes interpretation of the clinical data in these individuals.

In 1993, a large Dutch kindred with a new form of X-linked, non-dysmorphic, mild mental retardation was described by Dutch geneticist Han G. Brunner and colleagues at University Hospital Nijmegen in the Netherlands (Brunner et al 1993a). Affected males had a marked disturbance in their urinary monoamine profile that was compatible with a defect in monoamine oxidase. The locus for the disorder was assigned to the region of the monoamine oxidase-A gene. It was later reported by the same group that monoamine oxidase-A activity was deficient in dexamethasone-stimulated cultured skin fibroblasts from affected males and that monoamine oxidase-B activity was normal. The deficient monoamine oxidase-A activity was shown to be caused by a point mutation in exon 8 of the monoamine oxidase-A structural gene, which changes a glutamine (cytosine-adenosine-guanine) codon to a termination (thymidine-adenosine-guanine) codon (Brunner et al 1993b).

In 2001, another family was reported in whom monoamine oxidase deficiency was suspected on the basis of elevated serum serotonin concentrations. The affected mother presented with a history of flushes, headaches, and diarrhea. Her two sons had moderate intellectual impairment and attention deficit and hyperactivity disorder (Cheung and Earl 2001). Discussion relating to this family, pointed out that similar cases previously had been described (Warner 2002). In one study, nine individuals exhibited all of the same features: chronic episodic flushing, diarrhea, headache, psychiatric symptoms, irritability, prostration, increased blood serotonin, and normal or subnormal urinary 5-HIAA concentrations. Monoamine oxidase deficiency was suspected, and a number of metabolic studies were performed that supported the monoamine oxidase deficiency hypothesis (Warner 1963; Giannini et al 1986). Confirmation of the condition by enzyme or mutation analysis was not reported in any of these studies.

In 2010, two males were described with a 240kb deletion of Xp11.3-p11.4 that included both monoamine oxidase-A and B genes but excluded the Norrie disease gene (Whibley et al 2010). A similar case was reported in 2012 (O'Leary et al 2012). All had developmental delay, intermittent hypotonia, and stereotypic hand movements.

No specific defect affecting monoamine oxidase-B without involvement of the Norrie gene has been described.

Mouse models are available for deficiencies of both monoamine oxidase-A (Cases et al 1995; Scott et al 2008; Bortolato et al 2011a; Bortolato et al 2011b), monoamine oxidase-B (Grimsby et al 1997), and combined monoamine oxidase-A and B deficiency (Chen et al 2004; Bortolato and Shih 2011b; Singh et al 2013).

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