Pyruvate dehydrogenase complex deficiency, including:
Leigh syndrome;
Pyruvate dehydrogenase phosphatase deficiency;
Pyruvate dehydrogenase E3-binding protein deficiency (PDHXD)

Pyruvate dehydrogenase complex deficiency is an autosomal or X-linked recessive disorder caused by deficient enzyme activity in the pyruvate dehydrogenase complex, resulting in deficiency of acetyl CoA and reduced synthesis of acetylcholine. This deficiency in newborns may lead to brain malformations. Pyruvate dehydrogenase phosphatase (PDP) is an enzyme which regulates the activity of the pyruvate dehydrogenase complex. It has been reported that the mutations in PDP1 result in severe exercise intolerance and mild developmental delay.

Inherited metabolic disease; Neurodegenerative disease

PDHA1; pyruvate dehydrogenase E1 component subunit alpha 1 [HSA:5160] [KO:K00161]
PDHB; pyruvate dehydrogenase E1 component subunit beta [HSA:5162] [KO:K00162]
DLAT; pyruvate dehydrogenase E2 component, dihydrolipoamide acetyltransferase [HSA:1737] [KO:K00627]
DLD; dihydrolipoamide dehydrogenase [HSA:1738] [KO:K00382]
PDHX; pyruvate dehydrogenase complex component X [HSA:8050] [KO:K13997]
PPM2C; pyruvate dehyrogenase phosphatase catalytic subunit 1 [HSA:54704] [KO:K01102]
LRPPRC; Leucine-rich PPR motif-containing protein, mitochondrial [HSA:10128]

PMID:16854608

Robinson BH

Lactic acidemia and mitochondrial disease.

Mol Genet Metab 89:3-13 (2006)

PMID:16843025

Mine M, Brivet M, Schiff M, de Baulny HO, Chuzhanova N, Marsac C

A novel gross deletion caused by non-homologous recombination of the PDHX gene in a patient with pyruvate dehydrogenase deficiency.

Mol Genet Metab 89:106-10 (2006)

PMID:16156009

Pithukpakorn M

Disorders of pyruvate metabolism and the tricarboxylic acid cycle.

Mol Genet Metab 85:243-6 (2005)

PMID:12925875

Grafakou O, Oexle K, van den Heuvel L, Smeets R, Trijbels F, Goebel HH, Bosshard N, Superti-Furga A, Steinmann B, Smeitink J

Leigh syndrome due to compound heterozygosity of dihydrolipoamide dehydrogenase gene mutations. Description of the first E3 splice site mutation.

Eur J Pediatr 162:714-8 (2003)

PMID:10679936

Lissens W, De Meirleir L, Seneca S, Liebaers I, Brown GK, Brown RM, Ito M, Naito E, Kuroda Y, Kerr DS, Wexler ID, Patel MS, Robinson BH, Seyda A

Mutations in the X-linked pyruvate dehydrogenase (E1) alpha subunit gene (PDHA1) in patients with a pyruvate dehydrogenase complex deficiency.

Hum Mutat 15:209-19 (2000)

PMID:7853374

Brown GK, Otero LJ, LeGris M, Brown RM

Pyruvate dehydrogenase deficiency.

J Med Genet 31:875-9 (1994)

PMID:16574315

Maj MC, Cameron JM, Robinson BH

Pyruvate dehydrogenase phosphatase deficiency: orphan disease or an under-diagnosed condition?

Mol Cell Endocrinol 249:1-9 (2006)

PMID:12529507

Mootha VK, Lepage P, Miller K, Bunkenborg J, Reich M, Hjerrild M, Delmonte T, Villeneuve A, Sladek R, Xu F, Mitchell GA, Morin C, Mann M, Hudson TJ, Robinson B, Rioux JD, Lander ES

Identification of a gene causing human cytochrome c oxidase deficiency by integrative genomics.

Proc Natl Acad Sci U S A 100:605-10 (2003)

PMID:9399911

Aral B, Benelli C, Ait-Ghezala G, Amessou M, Fouque F, Maunoury C, Creau N, Kamoun P, Marsac C

Mutations in PDX1, the human lipoyl-containing component X of the pyruvate dehydrogenase-complex gene on chromosome 11p1, in congenital lactic acidosis.

Am J Hum Genet 61:1318-26 (1997)