Summary
Glutaryl-Coenzyme A (CoA) dehydrogenase deficiency (GDD) is an autosomal recessive neurometabolic disorder with an estimated incidence of 1:50,000 newborn Caucasians. It is caused by mutations in the glutaryl-CoA dehydrogenase gene localized on chromosome 19p13.2. Glutaryl-CoA dehydrogenase is a key mitochondrial enzyme in the catabolic pathways of the amino acids L-tryptophan, L-lysine, and L-hydroxylysine, that catalyzes the transformation of glutaryl-CoA into crotonyl-CoA. GDD is biochemically characterized by the accumulation of the dicarbonic glutaric acids, 3-hydroxyglutaric and glutaconic acids, and glutarylcarnitine. It is clinically characterized by a distinct neuropathology but only exceptionally presents with classical metabolic symptomatology, such as hypoglycemia or acidosis. During a vulnerable period of brain development, usually between the ages 6 and 12 months, a acute encephalopathy results in bilateral striatal damage via an excitotoxic mechanism and leads to a severe dystonic dyskinetic movement disorder. The preencephalopathic phase is unremarkable but most often progressive macrocephaly is apparent. Analysis of urinary organic acids in suspected patients aims at early detection of GDD or, analysis of acylcarnitine from dried blood spots may potentially become implemented in neonatal screening programs. Following presymptomatic detection, dietary treatment, carnitine supplementation and prompt intervention to treat intercurrent illnesses can be initiated early and have been shown to prevent acute neuronal damage in the majority of affected children. *Authors: Dr S. Kölker and Pr G.F. Hoffmann (June 2003)*
