Monoamine Oxidase A Deficiency

Classification according to ICD-10
E70.8	Other disorders of the metabolism of aromatic amino acids
ICD-10 online (WHO version 2019)

With monoamine oxidase-A deficiency is a very rare is congenital metabolic disorder with substantial loss of monoamine oxidase A and standing in the foreground impulsive aggression , respectively.

Synonyms are: MAO-A deficiency; Brunner Syndrome; English monoamine oxidase A deficiency; Brunner syndrome , outdated term: mental retardation, X-linked - anomalies of the MAOA metabolism

The name refers to the first author of the first description from 1993 by the Dutch human geneticist H. G. Brunner and colleagues.

distribution

The frequency is unknown; fewer than 20 people have been reported to be affected. The inheritance is X-linked - recessive .

root cause

The disease is based on mutations in the MAOA gene at the locus Xp11.3, which codes for monoamine oxidase A, so that monoamine oxidase fails completely.

Clinical manifestations

Clinical criteria are:

Slight intellectual deficit
Impulsive aggressiveness to violence
Beginning in childhood

history

In 1995, in a study on mice in which the MAOA gene had been switched off, increased levels of serotonin and noradrenaline were found in the brain and the behavior of the boys was classified as fearful and that of the adult animals as aggressive. These effects could be reversed by a substance that inhibited serotonin synthesis.

The members of a family described by Brunner in 1993 all had strongly changed monoamine levels in the urine and aggressive and mentally retarded behavior. The underlying point mutation in the MAOA gene led to a complete MAO-A deficiency. Other, more than a dozen other psychiatric studies in the period up to 2001, which examined possible associations between MAO-A and various mental illnesses, did not produce clear results. The families in Brunner's 1993 and 1999 studies were the only ones completely absent from MAO-A and exhibiting consistent behavior that was later called Brunner syndrome .

literature

M. Bortolato, JC Shih: Behavioral outcomes of monoamine oxidase deficiency: preclinical and clinical evidence. In: International review of neurobiology. Vol. 100, 2011, pp. 13-42, doi: 10.1016 / B978-0-12-386467-3.00002-9 , PMID 21971001 , PMC 3371272 (free full text) (review).

Individual evidence

↑ ^a ^b ^c Monoamine oxidase A deficiency. In: Orphanet (Rare Disease Database).
^ Mental retardation, X-linked abnormalities in MAOA metabolism. In: Orphanet (Rare Disease Database).
↑ HG Brunner, MR Nelen, P. van Zandvoort, NG Abeling, AH van Gennip, EC Wolters, MA Kuiper, HH Ropers, BA van Oost: X-linked borderline mental retardation with prominent behavioral disturbance: phenotype, genetic localization, and evidence for disturbed monoamine metabolism. In: American Journal of Human Genetics . Vol. 52, No. 6, June 1993, pp. 1032-1039, PMID 8503438 , PMC 1682278 (free full text).
^ Brunner syndrome. In: Online Mendelian Inheritance in Man . (English)
^ Cases O, Seif I, Grimsby J, et al. : Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA . In: Science . 268, No. 5218, June 1995, pp. 1763-1766. PMID 7792602 .
↑ Brunner HG, Nelen M, Breakefield XO, Ropers HH, van Oost BA: Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A . In: Science . 262, No. 5133, October 1993, pp. 578-580. PMID 8211186 .
↑ Table 1 in Shih JC, Thompson RF: Monoamine oxidase in neuropsychiatry and behavior . In: Am. J. Hum. Genet. . 65, No. 3, September 1999, pp. 593-598. doi : 10.1086 / 302562 . PMID 10441564 . PMC 1377964 (free full text).
↑ Jorm AF, Henderson AS, Jacomb PA, et al. : Association of a functional polymorphism of the monoamine oxidase A gene promoter with personality and psychiatric symptoms . In: Psychiatr. Genet. . 10, No. 2, June 2000, pp. 87-90. PMID 10994647 .
↑ Manuck SB, Flory JD, Ferrell RE, Mann JJ, Muldoon MF: A regulatory polymorphism of the monoamine oxidase-A gene may be associated with variability in aggression, impulsivity, and central nervous system serotonergic responsivity . In: Psychiatry Res . 95, No. 1, July 2000, pp. 9-23. PMID 10904119 .
^ Parsian A, Cloninger CR: Serotonergic pathway genes and subtypes of alcoholism: association studies . In: Psychiatr. Genet. . 11, No. 2, June 2001, pp. 89-94. PMID 11525423 .

Web links

[Orpha-1] Monoamine oxidase A deficiency. In: Orphanet (Rare Disease Database).

[2] Mental retardation, X-linked abnormalities in MAOA metabolism. In: Orphanet (Rare Disease Database).

[3] HG Brunner, MR Nelen, P. van Zandvoort, NG Abeling, AH van Gennip, EC Wolters, MA Kuiper, HH Ropers, BA van Oost: X-linked borderline mental retardation with prominent behavioral disturbance: phenotype, genetic localization, and evidence for disturbed monoamine metabolism. In: American Journal of Human Genetics . Vol. 52, No. 6, June 1993, pp. 1032-1039, PMID 8503438 , PMC 1682278 (free full text).

[4] Brunner syndrome. In: Online Mendelian Inheritance in Man . (English)

[5] Cases O, Seif I, Grimsby J, et al. : Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA . In: Science . 268, No. 5218, June 1995, pp. 1763-1766. PMID 7792602 .

[6] Brunner HG, Nelen M, Breakefield XO, Ropers HH, van Oost BA: Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A . In: Science . 262, No. 5133, October 1993, pp. 578-580. PMID 8211186 .

[7] Table 1 in Shih JC, Thompson RF: Monoamine oxidase in neuropsychiatry and behavior . In: Am. J. Hum. Genet. . 65, No. 3, September 1999, pp. 593-598. doi : 10.1086 / 302562 . PMID 10441564 . PMC 1377964 (free full text).

[8] Jorm AF, Henderson AS, Jacomb PA, et al. : Association of a functional polymorphism of the monoamine oxidase A gene promoter with personality and psychiatric symptoms . In: Psychiatr. Genet. . 10, No. 2, June 2000, pp. 87-90. PMID 10994647 .

[9] Manuck SB, Flory JD, Ferrell RE, Mann JJ, Muldoon MF: A regulatory polymorphism of the monoamine oxidase-A gene may be associated with variability in aggression, impulsivity, and central nervous system serotonergic responsivity . In: Psychiatry Res . 95, No. 1, July 2000, pp. 9-23. PMID 10904119 .

[10] Parsian A, Cloninger CR: Serotonergic pathway genes and subtypes of alcoholism: association studies . In: Psychiatr. Genet. . 11, No. 2, June 2001, pp. 89-94. PMID 11525423 .