Pyruvate dehydrogenase deficiency

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 1 Inheritance and pathophysiology 2 Presentation 3 Genetics 4 Treatment 5 References

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

Non-Mendelian inheritance: Mitochondrial diseases (277.87) Carbohydrate metabolism PCD · PDHA Primarily nervous system LHON · NARP · Leigh's Myopathies Mitochondrial encephalomyopathy (MELAS, MERRF) · KSS · PEO No primary system DAD · MNGIE · Pearson syndrome Chromosomal TIMM8A (Mohr-Tranebjaerg syndrome) · OPA1 (Kjer's optic neuropathy) see also mitochondrial proteins B 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), trfk

Disorders of TCA and ETC TCA PDHA · Fumarase deficiency ETC Coenzyme Q10 deficiency · Björnstad syndrome/GRACILE syndrome · Leigh's disease M: MET mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon m(A16/C10),i(k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)

Sex linkage: X-linked disorders X-linked recessive Immune Chronic granulomatous disease (CYBB) · Wiskott–Aldrich syndrome · X-linked severe combined immunodeficiency · X-linked agammaglobulinemia · Hyper-IgM syndrome type 1 · IPEX · X-linked lymphoproliferative disease · Properdin deficiency Hematologic Haemophilia A · Haemophilia B · X-linked sideroblastic anemia Endocrine Androgen insensitivity syndrome/Kennedy disease · KAL1 Kallmann syndrome · X-linked adrenal hypoplasia congenita Metabolic amino acid: Ornithine transcarbamylase deficiency · Oculocerebrorenal syndrome dyslipidemia: Adrenoleukodystrophy carbohydrate metabolism: Glucose-6-phosphate dehydrogenase deficiency · Pyruvate dehydrogenase deficiency · Danon disease/glycogen storage disease Type IIb lipid storage disorder: Fabry's disease mucopolysaccharidosis: Hunter syndrome purine-pyrimidine metabolism: Lesch–Nyhan syndrome mineral: Menkes disease/Occipital horn syndrome Nervous system X-Linked mental retardation: Coffin–Lowry syndrome · MASA syndrome · X-linked alpha thalassemia mental retardation syndrome · Siderius X-linked mental retardation syndrome eye disorders: Color blindness (red and green, but not blue) · Ocular albinism (1) · Norrie disease · Choroideremia other: Charcot–Marie–Tooth disease (CMTX2-3) · Pelizaeus–Merzbacher disease · SMAX2 Skin and related tissue Dyskeratosis congenita · Hypohidrotic ectodermal dysplasia (EDA) · X-linked ichthyosis · X-linked endothelial corneal dystrophy Neuromuscular Becker's muscular dystrophy/Duchenne · Centronuclear myopathy (MTM1) · Conradi–Hünermann syndrome · Emery–Dreifuss muscular dystrophy 1 Urologic Alport syndrome · Dent's disease · X-linked nephrogenic diabetes insipidus Bone/tooth AMELX Amelogenesis imperfecta No primary system Barth syndrome · McLeod syndrome · Smith-Fineman-Myers syndrome · Simpson–Golabi–Behmel syndrome · Mohr–Tranebjærg syndrome · Nasodigitoacoustic syndrome X-linked dominant X-linked hypophosphatemia · Focal dermal hypoplasia · Fragile X syndrome · Aicardi syndrome · Incontinentia pigmenti · Rett syndrome · CHILD syndrome · Lujan–Fryns syndrome · Orofaciodigital syndrome 1