Dihydrolipoamide dehydrogenase deficiency, also known as maple syrup urine disease type III, is a rare autosomal recessive disease of variable onset and severity. It is characterized by recurrent episodes of vomiting, abdominal pain, and encephalopathy. The onset of the disease is usually in early neonatal period, although later onsets have also been noted. Infants with this condition present with neonatal lactic acidosis, delayed psychomotor development, hypotonia, ataxia, dystonia, and seizures. Some patients may also show hepatomegaly and liver dysfunction. The severity of the condition varies highly, with some patients having normal psychomotor development. To date, about 20 patients with DLD deficiency have been reported worldwide.

Diagnosis of dihydrolipoamide dehydrogenase deficiency is based on clinical and biochemical features. Most patients show elevated blood levels of pyruvate, branched-chain amino acids, and alpha-ketoglutarate. Abnormal liver enzymes may also be seen in some patients. There is no cure for this disease. Dietary modifications may be helpful in slowing the progression of the disease, but are not always successful.

Dihydrolipoamide dehydrogenase deficiency is caused by mutations in the DLD gene. This gene encodes a mitochondrial enzyme called dihydrolipoamide dehydrogenase that oxidizes dihydrolipoamide to lipoamide. This enzyme also forms a subunit that is shared by several enzyme complexes, including the pyruvate dehydrogenase complex that plays an important role in converting pyruvate to acetyl-CoA within the cells. Most of the mutations in this gene that result in DLD Deficiency are single amino acid substitutions. The p.G229C missense mutation in this gene was found to be the most common mutation among the Ashkenazi Jewish origin.