3-methylglutacon aciduria type 1

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Classification according to ICD-10
E71.1 Other disorders of the metabolism of branched amino acids
ICD-10 online (WHO version 2019)

The 3-Methylglutaconazidurie type 1 is a very rare congenital , to the 3-Methylglutaconazidurien associated metabolic disorder with an enzyme defect in leucine -Metabolism and an increased excretion of 3-methylglutaconic acid and 3-methylglutaric acid in the urine .

Synonyms are: 3-methylglutaconyl-CoA hydratase deficiency; 3MG-coA hydratase deficiency; MGA type I; MGA1

The first description was probably made in 1976 by BH Robinson and colleagues.

pathology

It is an isolated 3-methylglutaconyl-CoA hydratase deficiency, the conversion of 3-methylglutaconyl-CoA into 3-hydroxy-3-mMethylglutaryl-CoA (HMG-CoA) is disturbed.

In contrast to the other types of 3-methylglutacon aciduria, this type can be regarded as the “primary” form.

distribution

The frequency is given as less than 1 in 1,000,000, so far about 20 people have been reported. Inheritance is autosomal - recessive .

root cause

Of the disease are mutations in the AUH - gene in the chromosome 9 at locus , which is involved in the metabolism of leucine-q22.31 based encoding for the 3-methylglutaconyl-CoA hydratase.

Clinical manifestations

The appearance varies , ranging from only mild language impairment to psychomotor retardation , coma , failure to thrive , metabolic acidosis and dystonia .

The onset of the disease is often in early childhood, but can also only become visible in adults as a neurodegenerative disease with ataxia , spasticity .

diagnosis

The diagnosis is made by determining the activity of 3-methylglutaconyl-CoA hydratase in fibroblasts or leukocytes or by measuring the excretion in the urine .

Compared to the other types of this group of diseases, the concentration of 3-methyl-glutaconic acid is significantly higher, and 3-hydroxy-isovaleric acid is only increased in type I.

In patients with signs of neurodegeneration, changes in the basal ganglia can often be detected on magnetic resonance imaging .

Differential diagnosis

The other types of 3-methylglutacon aciduria must be distinguished.

literature

  • AR Tavasoli, R. Shervin Badv, J. Zschocke, MR Ashrafi, P. Rostami: Early infantile presentation of 3-methylglutaconic aciduria type 1 with a novel mutation in AUH gene: A case report and literature review. In: Brain & development. Vol. 39, No. 8, September 2017, pp. 714-716, doi: 10.1016 / j.braindev.2017.04.007 , PMID 28438368 .
  • S. Mercimek-Mahmutoglu, T. Tucker, B. Casey: Phenotypic heterogeneity in two siblings with 3-methylglutaconic aciduria type I caused by a novel intragenic deletion. In: Molecular Genetics and Metabolism. Vol. 104, No. 3, November 2011, pp. 410-413, doi: 10.1016 / j.ymgme.2011.07.021 , PMID 21840233 .

Individual evidence

  1. ↑ a b c d 3-methylglutaconic aciduria type 1. In: Orphanet (database for rare diseases).
  2. ^ BH Robinson, WG Sherwood, M. Lampty, JA Lowden: β-Methylglutaconic aciduria: a new disorder of leucine metabolism. In: Pediatric Research Vol. 10, 1976, p. 371A
  3. ↑ L. IJlst, FJ Loupatty, JP Ruiter, M. Duran, W. Lehnert, RJ Wanders: 3-Methylglutaconic aciduria type I is caused by mutations in AUH. In: American Journal of Human Genetics . Vol. 71, No. 6, December 2002, pp. 1463-1466, doi: 10.1086 / 344712 , PMID 12434311 , PMC 378594 (free full text).
  4. ↑ SB Wortmann, M. Duran, Y. Anikster, PG Barth, W. Sperl, J. Zschocke, E. Morava, RA Wevers: Inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature: proper classification and nomenclature. In: Journal of inherited metabolic disease. Vol. 36, No. 6, November 2013, pp. 923-928, doi: 10.1007 / s10545-012-9580-0 , PMID 23296368 (review).
  5. ↑ a b 3-methylglutaconic aciduria, type I.  In: Online Mendelian Inheritance in Man . (English)
  6. ↑ A. Arbelaez, M. Castillo, J. Stone: MRI in 3-methylglutaconic aciduria type 1. In: Neuroradiology. Vol. 41, No. 12, December 1999, pp. 941-942, PMID 10639672 .

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