Lipoamide Dehydrogenase Deficiency (DLD)

Lipoamide dehydrogenase deficiency is an autosomal recessive disorder caused by pathogenic variants in the gene DLD. While patients have been observed from many different ethnicities, there is an increased prevalence in individuals of Ashkenazi Jewish descent due to the presence of a founder mutation. The classical form of this disease presents in infancy with severe and progressive neurological impairment, persistent lactic acidosis and high mortality. However, a continuum of disease severity exists, and some patients may be diagnosed in childhood, adolescence or adulthood with liver disease and no neurologic involvement. However, liver failure may be fatal in some patients. All individuals with liver disease and no neurologic involvement have been homozygous for the Ashkenazi Jewish founder mutation, but some individuals homozygous for this variant have also had the early onset form of the disease. Therefore, it is not currently possible to predict the severity of the disease based on genotype.

For information about carrier frequency and residual risk, please see the residual risk table.