Encyclopedia of Medical Immunology

Living Edition
| Editors: Ian MacKay, Noel R. Rose

3-Methylglutaconic Aciduria

  • Gesmar Rodrigues Silva SegundoEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-9209-2_140-1


3-methylglutaconic aciduria (3-MGA-uria) is a nonspecific biochemical finding related with a group of inborn errors of metabolism, particularly mitochondrial disorders. 3-MGA is a branched-chain organic acid and intermediate of leucine degradation and the mevalonate shunt pathway. The clinical features of the 3-MGA-uria syndromes are varied and are classified into five types, each with substantial heterogeneity. In all types, with the exception of 3-MGA-uria type I, the activities of 3-methylglutaconyl-CoA hydratase and other enzymes of leucine degradation are normal, and the 3-MGA-uria is considered secondary to defects in phospholipid remodeling or integrity of mitochondrial membranes, leading to electron transport chain dysfunction. 3-MGA-uria type I is an inborn error of leucine metabolism, caused by variants in AUH. AUHencodes 3-methylglutaconyl-CoA hydratase, which catalyzes the fifth step of leucine catabolism, whereby 3-methylglutaconyl-CoA is converted to...

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  1. Capo-Chichi JM, Boissel S, Brustein E, Pickles S, Fallet-Bianco C, Nassif C, et al. Disruption of CLPB is associated with congenital microcephaly, severe encephalopathy and 3-methylglutaconic aciduria. J Med Genet. 2015;52:303–11.CrossRefGoogle Scholar
  2. Kanabus M, Shahni R, Saldanha JW, Murphy E, Plagnol V, Hoff WV, et al. Bi-allelic CLPB mutations cause cataract, renal cysts, nephrocalcinosis and 3-methylglutaconic aciduria, a novel disorder of mitochondrial protein disaggregation. J Inherit Metab Dis. 2015;38:211–9.CrossRefGoogle Scholar
  3. Kiykim A, Garncarz W, Karakoc-Aydiner E, Ozen A, Kiykim E, Yesil G, et al. Novel CLPB mutation in a patient with 3-methylglutaconic aciduria causing severe neurological involvement and congenital neutropenia. Clin Immunol. 2016;165:1–3.CrossRefGoogle Scholar
  4. Saunders C, Smith L, Wibrand F, Ravn K, Bross P, Thiffault I, et al. CLPB variants associated with autosomal-recessive mitochondrial disorder with cataract, neutropenia, epilepsy, and methylglutaconic aciduria. Am J Hum Genet. 2015;96:258–65.CrossRefGoogle Scholar
  5. Wortmann SB, Ziętkiewicz S, Kousi M, Szklarczyk R, Haack TB, Gersting SW, et al. CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder. Am J Hum Genet. 2015;96:245–57.CrossRefGoogle Scholar

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© Springer Science+Business Media LLC 2018

Authors and Affiliations

  1. 1.Pediatrics Allergy and ImmunologyUniversidade Federal de UberlandiaUberlandiaBrazil

Section editors and affiliations

  • Antonio Condino-Neto
    • 1
  1. 1.Institute of Biomedical SciencesUniversity of São PauloSão PauloBrazil