Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013 Nov;36(6):923-8.
doi: 10.1007/s10545-012-9580-0. Epub 2013 Jan 8.

Inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature: proper classification and nomenclature

Saskia B Wortmann  1 , Marinus Duran, Yair Anikster, Peter G Barth, Wolfgang Sperl, Johannes Zschocke, Eva Morava, Ron A Wevers
Affiliations
Review

Inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature: proper classification and nomenclature

Saskia B Wortmann et al. J Inherit Metab Dis. 2013 Nov.

Abstract

Increased urinary 3-methylglutaconic acid excretion is a relatively common finding in metabolic disorders, especially in mitochondrial disorders. In most cases 3-methylglutaconic acid is only slightly elevated and accompanied by other (disease specific) metabolites. There is, however, a group of disorders with significantly and consistently increased 3-methylglutaconic acid excretion, where the 3-methylglutaconic aciduria is a hallmark of the phenotype and the key to diagnosis. Until now these disorders were labelled by roman numbers (I-V) in the order of discovery regardless of pathomechanism. Especially, the so called "unspecified" 3-methylglutaconic aciduria type IV has been ever growing, leading to biochemical and clinical diagnostic confusion. Therefore, we propose the following pathomechanism based classification and a simplified diagnostic flow chart for these "inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature". One should distinguish between "primary 3-methylglutaconic aciduria" formerly known as type I (3-methylglutaconyl-CoA hydratase deficiency, AUH defect) due to defective leucine catabolism and the--currently known--three groups of "secondary 3-methylglutaconic aciduria". The latter should be further classified and named by their defective protein or the historical name as follows: i) defective phospholipid remodelling (TAZ defect or Barth syndrome, SERAC1 defect or MEGDEL syndrome) and ii) mitochondrial membrane associated disorders (OPA3 defect or Costeff syndrome, DNAJC19 defect or DCMA syndrome, TMEM70 defect). The remaining patients with significant and consistent 3-methylglutaconic aciduria in whom the above mentioned syndromes have been excluded, should be referred to as "not otherwise specified (NOS) 3-MGA-uria" until elucidation of the underlying pathomechanism enables proper (possibly extended) classification.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Am J Hum Genet. 2002 Dec;71(6):1463-6 - PubMed
    1. NMR Biomed. 2006 Apr;19(2):271-8 - PubMed
    1. J Neurol Sci. 1983 Dec;62(1-3):327-55 - PubMed
    1. Development. 2010 Aug 1;137(15):2587-96 - PubMed
    1. Nat Genet. 2012 Jun 10;44(7):797-802 - PubMed

MeSH terms

Supplementary concepts

LinkOut - more resources