Dihydrolipoamide Dehydrogenase Deficiency

Gene : DLD

What is Dihydrolipoamide Dehydrogenase deficiency?

Dihydrolipoamide dehydrogenase deficiency (DLDD) is an inherited disorder caused by lack of the enzyme DLD which provides instructions for the breakdown of three amino acids present in many kinds of foods rich in protein. This leads to a toxic accumulation of these amino acids in the brain and other organs. Symptoms associated with DLDD have variable onset and severity, characterized by recurrent episodes of vomiting, abdominal pain, and brain dysfunction. Affected infants may also have feeding problems, fatigue, seizures, and death may occur soon after birth if the condition is not treated properly. The more severely affected individuals often have some degree of intellectual disability and growth deficiencies. Individuals with the more mild form of DLDD may only show symptoms of liver injury or failure, with no intellectual disability or neurologic deficit. Symptoms arise anytime from infancy into adulthood. There is currently no cure for DLDD, but efforts can be taken to alleviate the symptoms, including dietary restriction of the amino acids that cannot be broken down. However, dietary modifications may not always be effective. This deficiency is caused by pathogenic variants in the DLD gene.

How is Dihydrolipoamide Dehydrogenase deficiency inherited?

Dihydrolipoamide Dehydrogenase Deficiency is inherited in an autosomal recessive manner. This type of inheritance requires the presence of two copies of a pathogenic variant in the gene for a person to have the genetic disease. Both parents must be carriers of a pathogenic variant in the gene in order to be at risk to have an affected child. The child must inherit a pathogenic variant from each carrier parent in order to be affected. There is a 1 in 4 chance that a baby will inherit two mutated copies of the gene and be affected when both parents are carriers.

What does it mean to be a carrier?

There are no signs or symptoms associated with being a carrier DLDD. However, the risk to have a child affected with DLDD. Testing of reproductive partners is recommended for carriers of DLDD.

How common is Dihydrolipoamide Dehydrogenase deficiency?

DLDD is observed in 1 out of 925,000 newborns. This condition is relatively frequent in the Ashkenazi Jewish population, with about 1 out of 35,000 newborns affected.

Family References and Resources
Clinician References
What is Analyzed?
  • Full gene sequencing
Affected Systems

Brain

Muscle

Heart

Liver

GI Tract

Metabolic

Carrier Rates
Ethnicity
Detection Rate
Carrier Frequency
Ashkenazi Jewish 99% 1 in 94
General Population 96% 1 in 500

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