Dihydrolipoamide dehydrogenase deficiency

Preferred Label : Dihydrolipoamide dehydrogenase deficiency;

Symbol : DLDD;

CISMeF acronym : DLDD;

Type : Phenotype, molecular basis known;

Alternative titles and symbols : E3 deficiency; Lipoamide dehydrogenase deficiency, lactic acidosis due to; Dld deficiency; Maple syrup urine disease, type III; MSUD3;

Description : DLD deficiency is an autosomal recessive metabolic disorder characterized biochemically by a combined deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), pyruvate dehydrogenase complex (PDC), and alpha-ketoglutarate dehydrogenase complex (KGDC). This is the result of E3 being a common component of all 3 mitochondrial multienzyme complexes. Clinically, affected individuals have lactic acidosis and neurologic deterioration due to sensitivity of the central nervous system to defects in oxidative metabolism. E3 deficiency is often associated with increased urinary excretion of alpha-keto acids, such as pyruvate (summary by Hong et al., 1996). E3 deficiency can also be associated with increased concentrations of branched-chain amino acids, as observed in maple syrup urine disease (MSUD; 248600), and is sometimes referred to as 'MSUD type III,' although patients with E3 deficiency have additional biochemical defects (Chuang and Shih, 2001; Robinson, 2001).;

Inheritance : Autosomal recessive;

Molecular basis : Caused by mutation in the dihydrolipoamide dehydrogenase gene (DLD, 238331.0001);

Laboratory abnormalities : Elevated pyruvate (in most patients); Hypoglycemia; Abnormal liver enzymes (in some patients); Elevated branched-chain amino acids (in most patients); Decreased activities of the pyruvate dehydrogenase complex, the alpha-ketoglutarate dehydrogenase complex, and the branched-chain alpha-keto acid dehydrogenase complex; Elevated alpha-ketoglutarate (in most patients);

Prefixed ID : #246900;

Details

Origin ID

246900;

UMLS CUI

C5574660;

Automatic exact mappings (from CISMeF team)
- Pyruvate dehydrogenase complex E3 subunit deficiency [ICD-11 More detail]
- maple syrup urine disease [DO Concept]
Currated CISMeF NLP mapping
- Dihydrolipoamide dehydrogenase deficiency (disorder) [SNOMED CT concept]
- Pyruvate dehydrogenase E3 deficiency [ORDO Disease]
- dihydrolipoamide dehydrogenase deficiency [SNOMED Notion]
- dihydrolipoamide dehydrogenase deficiency [Disease (Nov.)]
- lactic acidosis, congenital infantile, due to LAD deficiency [MeSH Supplementary Concept]
- lactic acidosis, congenital infantile, due to LAD deficiency [MeSH concept]
DO Cross reference
- maple syrup urine disease [DO Concept]
Genes related to phenotype
- Dihydrolipoamide dehydrogenase [OMIM gene]
HPO term(s)
- Ataxia [HPO term]
- Autosomal recessive inheritance [HPO term]
- Decreased liver function [HPO term]
- Dystonia [HPO term]
- Elevated hepatic transaminase [HPO term]
- Encephalopathy [HPO term]
- Feeding difficulties [HPO term]
- Generalized hypotonia [HPO term]
- Global developmental delay [HPO term]
- Hepatomegaly [HPO term]
- Hypertrophic cardiomyopathy [HPO term]
- Hypoglycemia [HPO term]
- Hypotonia [HPO term]
- Lactic acidosis [HPO term]
- Lethargy [HPO term]
- Metabolic acidosis [HPO term]
- Microcephaly [HPO term]
- Seizure [HPO term]
- Variable expressivity [HPO term]
ORDO concept(s)
- Pyruvate dehydrogenase E3 deficiency [ORDO Disease]
- Pyruvate dehydrogenase deficiency [ORDO Disease]
Semantic type(s)
- Disease or Syndrome [UMLS semantic type]
UMLS correspondences (same concept)
- Autosomal recessive congenital methemoglobinemia (disorder) [SNOMED CT concept]
- Deficiency of cytochrome-b>5< reductase (disorder) [SNOMED CT concept]
- Dihydrolipoamide dehydrogenase deficiency (disorder) [SNOMED CT concept]
- NADH cytochrome B5 reductase deficiency [MeSH Supplementary Concept]
- NADH cytochrome B5 reductase deficiency [MeSH concept]
- NADH cytochrome b5 reductase deficiency [MedDRA LLT]
- cytochrome-b reductase deficiency [SNOMED Notion]
- dihydrolipoamide dehydrogenase deficiency [SNOMED Notion]

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