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Pathway Description
Pyruvate Dehydrogenase Complex Deficiency
Homo sapiens
Disease Pathway
Pyruvate dehydrogenase complex deficiency results from a mutation in the E1-alpha polypeptide gene (PDHA1). PDHA1 encodes the pyruvate dehydrogenase complex (PDC) a critical complex that converts pyruvate from glycolysis to acetyl CoA for the citric acid cycle. This conversion step links glycolysis and the citric acid cycle. A defect in this complex causes accumulation of lactate and pyruvate in the blood; lactate and pyruvic acid in the spinal fluid; and lactate in the urine. Symptoms include lactic and metabolic acidosis, motor retardation, dystonia, growth and mental retardation, and respiratory distress.
References
Pyruvate Dehydrogenase Complex Deficiency References
[Wikipedia: Pyruvate dehydrogenase deficiency](http://en.wikipedia.org/wiki/Pyruvate_dehydrogenase_deficiency)
[OMIM: Entry 312170](http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=312170)
[Uniprot: P08559](http://www.uniprot.org/uniprot/P08559)
Engelke, U., van der Graaf, M., Heerschap, A., Hoenderop, S., Moolenaar, S., Morava, E., Wevers, R. Handbook of 1H-NMR spectroscopy in inborn errors of metabolism: body fluid NMR spectroscopy and in vivo MR spectroscopy (2nd ed) (2007) p.120 Heilbronn: SPS Verlagsgesellschaft
Blass JP, Kark AP, Engel WK: Clinical studies of a patient with pyruvate decarboxylase deficiency. Arch Neurol. 1971 Nov;25(5):449-60.
Pubmed: 5110887
Brown GK, Otero LJ, LeGris M, Brown RM: Pyruvate dehydrogenase deficiency. J Med Genet. 1994 Nov;31(11):875-9.
Pubmed: 7853374
De Meirleir L, Specola N, Seneca S, Lissens W: Pyruvate dehydrogenase E1 alpha deficiency in a family: different clinical presentation in two siblings. J Inherit Metab Dis. 1998 Jun;21(3):224-6.
Pubmed: 9686362
Matthews PM, Brown RM, Otero LJ, Marchington DR, LeGris M, Howes R, Meadows LS, Shevell M, Scriver CR, Brown GK: Pyruvate dehydrogenase deficiency. Clinical presentation and molecular genetic characterization of five new patients. Brain. 1994 Jun;117 ( Pt 3):435-43.
Pubmed: 8032855
Brown GK, Brown RM, Scholem RD, Kirby DM, Dahl HH: The clinical and biochemical spectrum of human pyruvate dehydrogenase complex deficiency. Ann N Y Acad Sci. 1989;573:360-8.
Pubmed: 2517465
Pyruvate Metabolism References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Gray LR, Tompkins SC, Taylor EB: Regulation of pyruvate metabolism and human disease. Cell Mol Life Sci. 2014 Jul;71(14):2577-604. doi: 10.1007/s00018-013-1539-2. Epub 2013 Dec 21.
Pubmed: 24363178
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