Dihydrolipoamide dehydrogenase deficiency

What causes dihydrolipoamide dehydrogenase deficiency?

Dihydrolipoamide dehydrogenase (DLD) deficiency is caused by changes (mutations) in the DLD gene. This gene gives the body instructions to make an enzyme called dihydrolipoamide dehydrogenase (DLD). DLD is one part of 3 different groups of enzymes that work together (enzyme complexes). These enzyme complexes are involved in breaking down amino acids commonly found in protein-rich foods, and in other reactions that help to convert energy from food into a form that our cells can use.

Mutations in the DLD gene impair the function of DLD, preventing the 3 enzyme complexes from functioning properly. This causes a build-up of molecules that are normally broken down, which in turn leads to tissue damage, lactic acidosis and other chemical imbalances. The brain is especially sensitive to the buildup of molecules and lack of cellular energy, which is why there are neurological problems associated with DLD deficiency.

Last updated on 05-01-20

How is dihydrolipoamide dehydrogenase deficiency inherited?

Dihydrolipoamide dehydrogenase (DLD) deficiency is inherited in an autosomal recessive manner. This means that a person must have a mutation in both copies of the responsible gene in each cell to be affected. The parents of an affected person usually each carry one mutated copy of the gene and are referred to as carriers. Carriers typically do not have any signs or symptoms of the condition. When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) risk to be affected, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25% to be unaffected and not be a carrier.

Last updated on 05-01-20

What is the long-term outlook for people with dihydrolipoamide dehydrogenase deficiency?

The long-term outlook (prognosis) for people with dihydrolipoamide dehydrogenase (DLD) deficiency depends on the specific symptoms and severity in each person. Children diagnosed in the newborn period often do not survive their first episode or die within the first few years of life. However, multiple people have been reported surviving into their second and third decade of life. Those who survive past early childhood often have delayed growth and various neurological problems including intellectual disability, spasticity, ataxia, and seizures.

Those who become symptomatic after the neonatal period typically have milder signs and symptoms, with a significantly lower mortality rate. However, given the limited amount of information available in the medical literature, the degree of morbidity that surviving people experience is difficult to determine. The frequency of acute episodes reportedly decreases with age in most people with DLD deficiency.

Last updated on 05-01-20

How might dihydrolipoamide dehydrogenase deficiency be treated?

There are currently no consensus recommendations for the management of dihydrolipoamide dehydrogenase (DLD) deficiency. Management can be hard because various metabolic pathways are affected and 3 enzyme complexes are involved. Deficiencies in enzyme pathways vary depending on the specific mutation(s) each affected person has.

Unfortunately, the treatments that have been attempted in children with the early-onset neurologic form do not appear to significantly alter the course of the disease. Even with treatment, children often do not survive infancy or have varying degrees of chronic neurologic impairment if they survive the initial episode. Depending on individual enzyme complex deficiencies, treatment may involve certain dietary restrictions or certain diets; use of medical foods; and/or supplementation of specific amino acids or other substances.

There is limited data for the chronic management of people with the primarily hepatic (liver-related) form of the disease. Management typically involves supportive therapy during times of acute liver injury or failure, and may include nutritional support; IV glucose for hypoglycemia; correction of metabolic acidosis; correction of coagulopathy; and avoidance of liver-toxic medications.

More detailed information about the management of DLD deficiency can be viewed on the GeneReviews Web site. GeneReviews is intended for use by genetics professionals. Those not familiar with the principles discussed on the GeneReviews Web site are encouraged to speak with a genetics professional or other healthcare provider regarding information of interest.

Last updated on 05-01-20

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