Disorders of the γ-glutamyl cycle

Abstract

This chapter is concerned with the treatment the following disorders: 2-ketoglutarate dehydrogenase complex deficiency (2-ketoglutarate dehydrogenase deficiencyanddihydrolipoamide S-succinyltransferse deficiency); fumarasedeficiency; malonyl CoA decarboxylase deficiency; l-2-hydroxyglutaric aciduria; d-2-hydroxyglutaric aciduria and aspartoacylase deficiency (Canavan disease) (see Nomenclature section). 2-Ketoglutarate dehydrogenase and fumarase deficiency are disorders involving enzymes of theKrebs cycle; malonyl CoA decarboxylase is responsible for the conversion of intramitochondrial malonyl-CoA to acetyl-CoA and plays an important role in fatty acid oxidation; no enzyme deficiencies have yet been found for either l-2-hydroxyglutaric aciduria or d-2-hydroxyglutaric aciduria; aspartoacylase is a key enzyme within the central nervous system. All these disorders are rare. In the section Clinical Features and Prognosis is a summary of the clinical presentation and prognosis of these disorders. The method of diagnosis and further details of the clinical presentation are described in the corresponding chapter of the Physicians Guide to the Laboratory Diagnosis of Metabolic Diseases.