Dihydrolipoamide Dehydrogenase Deficiency

Alternative Names

  • DLDD
  • DLD Deficiency
  • E3 Deficiency
  • Lipoamide Dehydrogenase Deficiency, Lactic Acidosis due to
  • Maple Syrup Urine Disease, Type III
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WHO-ICD-10 version:2010

Endocrine, nutritional and metabolic diseases

Metabolic disorders

OMIM Number

246900

Mode of Inheritance

Autosomal recessive

Gene Map Locus

7q31.1

Description

Dihydrolipoamide dehydrogenase deficiency, also known as maple syrup urine disease type III, is a rare autosomal recessive disease of variable onset and severity. It is characterized by recurrent episodes of vomiting, abdominal pain, and encephalopathy. The onset of the disease is usually in early neonatal period, although later onsets have also been noted. Infants with this condition present with neonatal lactic acidosis, delayed psychomotor development, hypotonia, ataxia, dystonia, and seizures. Some patients may also show hepatomegaly and liver dysfunction. The severity of the condition varies highly, with some patients having normal psychomotor development. To date, about 20 patients with DLD deficiency have been reported worldwide.

Diagnosis of dihydrolipoamide dehydrogenase deficiency is based on clinical and biochemical features. Most patients show elevated blood levels of pyruvate, branched-chain amino acids, and alpha-ketoglutarate. Abnormal liver enzymes may also be seen in some patients. There is no cure for this disease. Dietary modifications may be helpful in slowing the progression of the disease, but are not always successful.

Molecular Genetics

Dihydrolipoamide dehydrogenase deficiency is caused by mutations in the DLD gene. This gene encodes a mitochondrial enzyme called dihydrolipoamide dehydrogenase that oxidizes dihydrolipoamide to lipoamide. This enzyme also forms a subunit that is shared by several enzyme complexes, including the pyruvate dehydrogenase complex that plays an important role in converting pyruvate to acetyl-CoA within the cells. Most of the mutations in this gene that result in DLD Deficiency are single amino acid substitutions. The p.G229C missense mutation in this gene was found to be the most common mutation among the Ashkenazi Jewish origin.

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
246900.1.1PalestineFemaleYesYes Death in infancy; Episodic vomiting; ...NM_000108.5:c.685G>THomozygousAutosomal, RecessiveHong et al. 2003 The patient had two ...
246900.1.2PalestineMaleYesYes Episodic vomiting; Encephalopathy; ...NM_000108.5:c.685G>THomozygousAutosomal, RecessiveHong et al. 2003 Brother of 246900.1....
246900.2.1AlgeriaMaleYesYes Death in childhood; Axial hypotonia; R...NM_000108.5:c.1444A>GHomozygousAutosomal, RecessiveOdièvre et al. 2005; Bonnefont et al, 1992
246900.2.2AlgeriaMaleYesYes Death in childhood; Axial hypotonia; ...NM_000108.5:c.1444A>GHomozygousAutosomal, RecessiveOdièvre et al. 2005; Bonnefont et al, 1992 Brother of 246900.2....
246900.2.3AlgeriaMaleYesYes Death in infancy; Axial hypotonia; ...NM_000108.5:c.1444A>GHomozygousAutosomal, RecessiveOdièvre et al. 2005; Bonnefont et al, 1992 Brother of 246900.2....
246900.3PalestineMaleYes Respiratory distress; Left ventricular h...NM_000108.5:c.1436A>THomozygousAutosomal, RecessiveAl-Jasmi et al. 2016
246900.4PalestineMaleYes Lactic acidosis; Nystagmus; Sensorineura...NM_000108.5:c.1436A>THomozygousAutosomal, RecessiveAl-Jasmi et al. 2016
246900.5United Arab EmiratesMaleYes Vomiting; Seizure; Hypoglycemia; Global ...NM_000108.5:c.685G>THomozygousAutosomal, RecessiveAl-Jasmi et al. 2016
246900.6Saudi ArabiaFemale Delayed speech and language development;...NM_000108.5:c.685G>THomozygousAutosomal, RecessiveMonies et al. 2017
246900.G.1United Arab EmiratesNM_000108.5:c.685G>THomozygousAutosomal, RecessiveAl-Shamsi et al. 2014 Group of 2 patients
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