Dihydrolipoamide dehydrogenase deficiency, which is also known as DLDD, DLD, E3 deficiency, pyruvate dehydrogenase E3 deficiency, DLD deficiency, E3-deficient maple syrup urine disease, is a rare inherited inborn error of metabolism. DLD deficiency occurs in an estimated 1 in 35 000 to 48 000 individuals of Ashkenazi Jewish descent. DLDD is an autosomal recessive metabolic disorder characterized by mutations to the DLD gene, which codes for dihydrolipoamide dehydrogenase (DLD). DLD is a flavoprotein enzyme that oxidizes dihydrolipoamide to lipoamide. The DLD homodimer functions as the E3 component of the pyruvate, alpha-ketoglutarate, and branched-chain amino acid-dehydrogenase complexes and the glycine cleavage system, all of which are located in the mitochondrial matrix. DLDD is a combined deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), pyruvate dehydrogenase complex (PDC), and alpha-ketoglutarate dehydrogenase complex (KGDC). A common feature of dihydrolipoamide dehydrogenase deficiency is a potentially life-threatening buildup of lactic acid in tissues (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat. Neurological problems are also common in this condition; the first symptoms in affected infants are often decreased muscle tone (hypotonia) and extreme tiredness (lethargy). E3 deficiency is often associated with increased urinary excretion of alpha-keto acids, such as pyruvate. E3 deficiency can also be associated with increased concentrations of branched-chain amino acids, as observed in maple syrup urine disease (MSUD) and is sometimes referred to as MSUD type III, although patients with E3 deficiency have additional biochemical defects.

Pyruvate Dehydrogenase Deficiency (E3) References