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

Saskia B. Wortmann, Marinus Duran, Yair Anikster, Peter G. Barth, Wolfgang Sperl, Johannes Zschocke, Eva Morava-Kozicz, Ron A. Wevers

Research output: Contribution to journalArticle

46 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)923-928
Number of pages6
JournalJournal of Inherited Metabolic Disease
Volume36
Issue number6
DOIs
StatePublished - Nov 1 2013
Externally publishedYes

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Inborn Errors Metabolism
Terminology
Barth Syndrome
Mitochondrial Diseases
Mitochondrial Membranes
Leucine
Names
Phospholipids
3-Methylglutaconic Aciduria
Phenotype
3-methylglutaconic acid
Proteins

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature : Proper classification and nomenclature. / Wortmann, Saskia B.; Duran, Marinus; Anikster, Yair; Barth, Peter G.; Sperl, Wolfgang; Zschocke, Johannes; Morava-Kozicz, Eva; Wevers, Ron A.

In: Journal of Inherited Metabolic Disease, Vol. 36, No. 6, 01.11.2013, p. 923-928.

Research output: Contribution to journalArticle

Wortmann, Saskia B. ; Duran, Marinus ; Anikster, Yair ; Barth, Peter G. ; Sperl, Wolfgang ; Zschocke, Johannes ; Morava-Kozicz, Eva ; Wevers, Ron A. / Inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature : Proper classification and nomenclature. In: Journal of Inherited Metabolic Disease. 2013 ; Vol. 36, No. 6. pp. 923-928.
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AU - Barth, Peter G.

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