- Pyruvate dehydrogenase deficiency
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Pyruvate dehydrogenase deficiency Classification and external resources ICD-10 E74.4 ICD-9 271.8 OMIM 312170 DiseasesDB 30060 eMedicine ped/1969 MeSH D015325 Pyruvate Dehydrogenase Deficiency (PDH) is a genetic disease that involves human metabolism.
Contents
Inheritance and pathophysiology
It most commonly follows an X-linked inheritance pattern, but is approximately equally prevalent in both males and females. This is because heterozygote females commonly manifest severe symptoms, an unusual situation in X-linked conditions. 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.
Deficiencies of the regulatory complex (pyruvate dehydrogenase phosphatase) have also been investigated.[1]
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.
Genetics
PDH deficiency is most commonly linked to the alpha unit of E1, which is X-linked, but autosomal recessive variants also exist.
Treatment
Use of a ketogenic diet has been described.[2]
Current research is being conducted on the viability of Dichloroacetic acid to treat the lactic acidosis commonly accompanied by this disorder.[3][4] Additionally, there is research being conducted on the viability of gene therapy for sufferers of this condition as well as many other mitochondrial defects.
References
- ^ Maj MC, Cameron JM, Robinson BH (April 2006). "Pyruvate dehydrogenase phosphatase deficiency: orphan disease or an under-diagnosed condition?". Mol. Cell. Endocrinol. 249 (1-2): 1–9. doi:10.1016/j.mce.2006.02.003. PMID 16574315. http://linkinghub.elsevier.com/retrieve/pii/S0303-7207(06)00051-7.
- ^ Barañano KW, Hartman AL (November 2008). "The ketogenic diet: uses in epilepsy and other neurologic illnesses". Curr Treat Options Neurol 10 (6): 410–9. doi:10.1007/s11940-008-0043-8. PMC 2898565. PMID 18990309. http://www.treatment-options.com/1092-8480/10/410.[dead link]
- ^ Berendzen K, Theriaque DW, Shuster J, Stacpoole PW (June 2006). "Therapeutic potential of dichloroacetate for pyruvate dehydrogenase complex deficiency". Mitochondrion 6 (3): 126–35. doi:10.1016/j.mito.2006.04.001. PMID 16725381. http://linkinghub.elsevier.com/retrieve/pii/S1567-7249(06)00056-0.
- ^ Stacpoole PW, Kurtz TL, Han Z, Langaee T (2008). "Role of dichloroacetate in the treatment of genetic mitochondrial diseases". Adv. Drug Deliv. Rev. 60 (13-14): 1478–87. doi:10.1016/j.addr.2008.02.014. PMID 18647626. http://linkinghub.elsevier.com/retrieve/pii/S0169-409X(08)00161-0.
Non-Mendelian inheritance: Mitochondrial diseases (277.87) Carbohydrate metabolism PCD · PDHAPrimarily nervous system Myopathies No primary system Chromosomal see also mitochondrial proteinsB structural (perx, skel, cili, mito, nucl, sclr) · DNA/RNA/protein synthesis (drep, trfc, tscr, tltn) · membrane (icha, slcr, atpa, abct, othr) · transduction (iter, csrc, itra), trfkPDHA · Fumarase deficiencyETC 
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