Dihydrolipoamide Dehydrogenase Deficiency
Pyruvate dehydrogenase deficiency (PDHD) is a rare neurometabolic disorder characterized by a wide range of clinical signs with metabolic and neurological components of varying severity. Manifestations range from often fatal, severe, neonatal lactic acidosis to later-onset neurological disorders.
The disorder is caused by mutations in the DLD gene (7q31-q32). The pattern of inheritance is autosomal recessive. The main mutation is c.685G>T (p.Gly229Cys). In the Ashkenazi Jew population, the carrier frequency of this pathogenic variant is estimated between 1/94 and 1/110 with an estimated disease frequency of 1/35,000 to 1/48,000.
Most of the patients present neonatal lactic acidosis, developmental delay and hypotonia during childhood. A few patients present in childhood ataxia and dystonia with normal cognitive development. May appear episodes of vomiting, abdominal pain, encephalopathy, and liver cell dysfunction. In some patients, there is evidence of a dehydrogenase deficiency of branched-chain alpha-ketoacids, with high concentrations of branched-chain amino acids and their metabolites. However, clinical manifestations appear to be related in most cases to pyruvate dehydrogenase deficiency.
Gene or region studied