Dihydrolipoamide dehydrogenase deficiency is an inherited metabolic condition that is most often characterized by early-onset lactic acidosis (excess lactic acid in the body) and delayed development.
Symptoms include hypotonia and lethargy in infancy, feeding difficulties, seizures, and lactic acidosis shortly after birth, which can cause nausea, vomiting, severe breathing problems and an abnormal heartbeat. Liver problems ranging from hepatomegaly to life-threatening liver failure often accompany this condition as well. Affected infants often do not survive past their first few years of life, however those that do survive often have growth delays, intellectual disability, spasticity, ataxia, and seizures. There is no successful treatment for this disease other than treating the symptoms.
This condition is caused by pathogenic (disease-causing) variants in the DLD gene and exhibits autosomal recessive inheritance, meaning that both parents must be carriers to have a 25% chance to have a child with this condition. Carriers of this genetic mutation do not typically display any signs or symptoms. The risk of being a carrier is based on a person’s ancestry or ethnic background. For example, individuals of Ashkenazi Jewish descent have a higher incidence of this condition than the general population, with a carrier frequency of 1 in 107.
Other names for this condition include lipoamide dehydrogenase deficiency and E3 deficiency.
Resources:
Genetic and Rare Diseases Information Center (GARD)
Revised October 2023
