Dihydrolipoamide Dehydrogenase Deficiency

Dihydrolipoamide dehydrogenase deficiency is an autosomal recessive disease affecting metabolism, usually occurring in infancy and characterized by lactic acidosis and growth retardation. It may have a late onset and lead to liver dysfunction.

Dihydrolipoamide dehydrogenase deficiency is a rare metabolic disorder causing neurological and hepatic impairment. Specific changes in urinary and plasma metabolite levels are the hallmark of the disease.

It is a pathology caused by variants in the DLD gene with an autosomal recessive inheritance pattern and its prevalence in the general population is less than 1 case per 1,000,000 inhabitants.

Symptoms

Symptoms may have an early onset with neurological manifestations or begin in adults, usually with liver failure.

Most commonly, the disease develops in childhood with growth retardation, neurological disturbances (intellectual disability, spasticity, ataxia and seizures) and hypotonia with lactic acidosis. Liver failure may present as early as childhood and is the typical symptom in patients with late onset of the disease.

Acute metabolic episodes are frequently associated with lactate elevations, hyperammonemia and hepatomegaly or enlarged liver. Less frequently patients may present with myopathy (muscle cramps, weakness and elevated creatine kinase).

Disease management

Following a specific diet supervised by specialists in metabolic diseases and avoiding certain medications that may damage the liver. Routine medical visits to monitor liver function and follow-up of peripheral neuropathy.

Genes analyzed

DLD

Bibliography

Brassier A, Ottolenghi C, Boutron A, et al . Dihydrolipoamide dehydrogenase deficiency: a still overlooked cause of recurrent acute liver failure and Reye-like syndrome. Mol Genet Metab. 2013 May;109(1):28-32.

Quinonez SC, Thoene JG. Dihydrolipoamide Dehydrogenase Deficiency. 2014 Jul 17 [updated 2021 Sep 30]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022.

Szabo E, Wilk P, Nagy B, et al . Underlying molecular alterations in human dihydrolipoamide dehydrogenase deficiency revealed by structural analyses of disease-causing enzyme variants. Hum Mol Genet. 2019 Oct 15;28(20):3339-3354.

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