Alpha 2.0
Login Register
» Articles » PMID: 12434311

3-Methylglutaconic Aciduria Type I is Caused by Mutations in AUH

Overview
Journal Am J Hum Genet
Publisher Cell Press
Specialty Genetics
Date 2002 Nov 16
PMID 12434311
Citations 33
Authors
Lodewijk Ijlst
Ference J Loupatty
Jos P N Ruiter
Marinus Duran
Willy Lehnert
Ronald J A Wanders
Affiliations
Soon will be listed here.
Abstract

3-Methylglutaconic aciduria type I is an autosomal recessive disorder clinically characterized by various symptoms ranging from delayed speech development to severe neurological handicap. This disorder is caused by a deficiency of 3-methylglutaconyl-CoA hydratase, one of the key enzymes of leucine degradation. This results in elevated urinary levels of 3-methylglutaconic acid, 3-methylglutaric acid, and 3-hydroxyisovaleric acid. By heterologous expression in Escherichia coli, we show that 3-methylglutaconyl-CoA hydratase is encoded by the AUH gene, whose product had been reported elsewhere as an AU-specific RNA-binding protein. Mutation analysis of AUH in two patients revealed a nonsense mutation (R197X) and a splice-site mutation (IVS8-1G-->A), demonstrating that mutations in AUH cause 3-methylglutaconic aciduria type I.

Citing Articles

Mitochondrial membrane synthesis, remodelling and cellular trafficking.

Messina M, Vaz F, Rahman S J Inherit Metab Dis. 2024; 48(1):e12766.

PMID: 38872485 PMC: 11730691. DOI: 10.1002/jimd.12766.

Genetic outcomes in children with developmental language disorder: a systematic review.

van Wijngaarden V, de Wilde H, Mink van der Molen D, Petter J, Stegeman I, Gerrits E Front Pediatr. 2024; 12:1315229.

PMID: 38298611 PMC: 10828955. DOI: 10.3389/fped.2024.1315229.

Asymptomatic 3-methylglutaconic aciduria type 1 detected by high C5-OH on newborn screening.

Itonaga T, Maeda M, Koga H, Hasegawa Y, Ihara K Mol Genet Metab Rep. 2023; 38:101024.

PMID: 38077954 PMC: 10709048. DOI: 10.1016/j.ymgmr.2023.101024.

N-acetylglutamate synthase deficiency with associated 3-methylglutaconic aciduria: A case report.

Selvanathan A, Demetriou K, Lynch M, Lipke M, Bursle C, Elliott A JIMD Rep. 2022; 63(5):420-424.

PMID: 36101823 PMC: 9458610. DOI: 10.1002/jmd2.12318.

Diversion of Acetyl CoA to 3-Methylglutaconic Acid Caused by Discrete Inborn Errors of Metabolism.

Jones D, Jennings E, Ryan R Metabolites. 2022; 12(5).

PMID: 35629880 PMC: 9146172. DOI: 10.3390/metabo12050377.

References
1.
Narisawa K, Gibson K, Sweetman L, Nyhan W . 3-Methylglutaconyl-CoA hydratase, 3-methylcrotonyl-CoA carboxylase and 3-hydroxy-3-methylglutaryl-CoA lyase deficiencies: a coupled enzyme assay useful for their detection. Clin Chim Acta. 1989; 184(1):57-64. DOI: 10.1016/0009-8981(89)90256-8. View
2.
Ensenauer R, Muller C, Schwab K, Gibson K, Brandis M, Lehnert W . 3-Methylglutaconyl-CoA hydratase deficiency: a new patient with speech retardation as the leading sign. J Inherit Metab Dis. 2000; 23(4):341-4. DOI: 10.1023/a:1005670911799. View
3.
Kurimoto K, Fukai S, Nureki O, Muto Y, Yokoyama S . Crystal structure of human AUH protein, a single-stranded RNA binding homolog of enoyl-CoA hydratase. Structure. 2001; 9(12):1253-63. DOI: 10.1016/s0969-2126(01)00686-4. View
4.
Duran M, Beemer F, Tibosch A, Bruinvis L, Ketting D, WADMAN S . Inherited 3-methylglutaconic aciduria in two brothers--another defect of leucine metabolism. J Pediatr. 1982; 101(4):551-4. DOI: 10.1016/s0022-3476(82)80698-7. View
5.
Narisawa K, Gibson K, Sweetman L, Nyhan W, Duran M, WADMAN S . Deficiency of 3-methylglutaconyl-coenzyme A hydratase in two siblings with 3-methylglutaconic aciduria. J Clin Invest. 1986; 77(4):1148-52. PMC: 424450. DOI: 10.1172/JCI112415. View