, Volume 156, Issue 11, pp 821-828
Date: 04 Dec 2012

Glutaric aciduria type 1 (glutaryl-CoA-dehydrogenase deficiency): advances and unanswered questions

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Abstract

Infants with macrocephaly, young children with acute disease resembling encephalitis, and children with truncal hypotonia, ataxia, or dystonia may be affected by glutaric aciduria type I (GA 1, glutaryl-CoA-dehydrogenase deficiency), a not-so-rare autosomal recessive neurometabolic disease. Well-known features of GA1 are fronto-temporal brain atrophy with macrocephaly and acute encephalopathic episodes with striatal necrosis followed by dystonia, but some patients develop motor disease without overt crises and other biochemically affected individuals remain asymptomatic. Biochemical and molecular characterization is available and allows post- and prenatal diagnosis. The pathogenesis of fronto-temporal atrophy, macrocephaly, and basal ganglia necrosis is still not understood, and there is no close correlation between biochemical parameters and clinical outcome. There is, however, evidence suggesting that carnitine supplementation and anticatabolic treatment of intercurrent illness may arrest or prevent neurological deterioration, while the role of limitation of dietary lysine and tryptophane is not yet clear. Although pathogenetic aspects are poorly understood, the natural course of glutaric aciduria type 1 can be changed by early diagnosis and treatment. Coordinated research is needed to understand the pathogenesis of brain toxicity, to define the role of dietary therapy, and to explore the possibility of neonatal screening.

The 2nd European Workshop on Glutaryl-CoA Dehydrogenase Deficiency, organized by G.F. Hoffmann (University of Marburg), was held on 29 September to 2 October 1996, in Schloss Rauischholzhausen (FRG). Speakers and chairmen were Buckel (Marburg), R.A. Chalmers (London), E. Christensen (Copenhagen), J.B.C. de Klerk (Rotterdam), R. Duran (Utrecht), O. Elpeleg (Jerusalem), S.I. Goodman (Denver), G.F. Hoffmann (Marburg), C. Jakobs (Amsterdam), B. Johnels (Göteborg), M. Kyllerman (Goöteborg), J. Leonard (London), D.H. Morton (Strasburg), E. Müller (Heidelberg), E. Naughton (Dublin), J.-M. Saudubray (Paris), A. Superti-Furga (Zürich). The contribution of speakers, chairmen and participants is acknowledged, while the authors take full responsibility for the opinions presented in the present paper. The Workshop has been supported by the HELIOS II Programme of the European Community, the Deutsche Forschungsgemeinschaft, and MILUPA AG, Germany