dihydrolipoamide dehydrogenase deficiency
Definition An autosomal recessive metabolic disorder (OMIM:246900) characterised by lactic acidosis and neurologic deterioration.
Clinical findings Lactic acidosis and neurologic deterioration due to sensitivity of the CNS to defective oxidative metabolism.
Biochemical findings Combined deficiency of:
• Alpha-ketoglutarate dehydrogenase complex
• Branched-chain alpha-keto acid dehydrogenase complex
• Pyruvate dehydrogenase complex
Molecular pathology Defects of DLD, which encodes a moonlighting protein that, as a homodimer, regulates energy metabolism and as a monomer acts as a protease, cause dihydrolipoamide dehydrogenase deficiency.
Synonyms DLD deficiency, E3 deficiency, lactic acidosis due to maple syrup urine diseasetype III, lipoamide dehydrogenase deficiency