Pyruvate dehydrogenase deficiency

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Pyruvate dehydrogenase deficiency Classification and external resources
ICD-10	E74.4
OMIM	312170
DiseasesDB	30060
eMedicine	ped/1969
MeSH	D015325

Pyruvate Dehydrogenase Deficiency (PDH) is a human genetic disease. It follows a dominant inheritance pattern, but is approximately equally prevalent in both males and females, though where there is only one copy of the gene involved from the mother, male foetuses may not be viable. Due to the genes involved being essential to life, some of the genetic causes are extremely rare, in the order of 1 in millions. It affects a gene which codes for a critical enzyme complex, the Pyruvate dehydrogenase complex (PDC) which links the metabolic pathways of glycolysis and the citric acid cycle by transforming pyruvate into Acetyl CoA

The pyruvate dehydrogenase complex facilitates oxidative decarboxylation, the chemical reaction between glycolysis and the citric acid cycle.

[edit] Presentation

PDH causes Lactic acidosis; large amounts of lactic acid in the blood but with a normal pyruvate/lactate ratio. Symptoms are varied, and include developmental defects (especially of the brain and nervous system), muscular spasticity and early death.

[edit] Genetics

PDH is most commonly linked to the alpha unit of E1, but recessive variants exist.

v • d • e Mitochondrial diseases Myopathies MELAS - MERRF - KSS - PEO Other DAD - Friedreich's ataxia - LHON - Leigh's - NARP - MNGIE - PCD - PDHA - Pearson syndrome

v • d • e Inborn error of carbohydrate metabolism (including glycogen storage diseases) (E73-74, 271) Disaccharide catabolism Lactose intolerance - Sucrose intolerance Monosaccharide catabolism fructose: Essential fructosuria - Fructose intolerance galactose/galactosemia : Galactokinase deficiency - Galactose-1-phosphate uridylyltransferase galactosemia - Galactose epimerase deficiency Monosaccharide transport Glucose-galactose malabsorption - Inborn errors of renal tubular transport (Renal glycosuria) Glycolysis GSD type VII, Tarui's, phosphofructokinase - Triosephosphate isomerase deficiency - Pyruvate kinase deficiency Pyruvate catabolism PDHA - Fumarase deficiency Gluconeogenesis PCD - Fructose bisphosphatase deficiency - GSD type I, von Gierke, glucose 6-phosphatase Glycogenesis GSD type 0, glycogen synthase - GSD type IV, Andersen's, branching Glycogenolysis GSD type II, Pompe's, glucosidase - GSD type III, Cori's, debranching - GSD type V, McArdle, glycogen phosphorylase/GSD type VI, Hers', glycogen phosphorylase - GSD type I, von Gierke, glucose 6-phosphatas Pentose phosphate pathway Glucose-6-phosphate dehydrogenase deficiency - Pentosuria Other Hyperoxaluria see also glycolysis enzymes, pentose phosphate pathway enzymes, fructose and galactose metabolism enzymes