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Pyruvate Dehydrogenase Complex Deficiency, also know as PDCD, PDHA or congenital lactic acidemia. PDCD is a genetic disorder that is due to malfunctions in the TCA cycle, or Tricarboxylic Acid cylce (Krebs Cycle). media type="custom" key="3627057" width="332" height="346"
 * //__Introduction__//**

This rare disorder by the name of Pyruvate dehydrogenase complex deficiency (PDCD) is a disorder of carbohydrate metabolism which is caused by a deficiency of one or more of the enzymes in the pyruvate dehydrogenase complex. Most commonly, the X chromosome is the trait which is damsged and is the actual cause for the deficiency and is also a sex-linked, dormant trait. The severity of PDCD depends on the activity level of the PDC enzymes. Children that are born with PDCD usually die young if the deficiency occured in the beginning of prenatal or during infancy. If and individual were to develop PDCD later on in their childhood it may lead to mental retardation and/or other neurological symptoms, but usually do survive into adulthood. Approximately 25% of individuals with PDCD have an abnormality in one of their genes. PHE1A is the gene that contains the abnormality and is located on the X chromosome. Approximately 75% of the affected individuals have a form of the disorder that of which follows an autosomal recessive inheritance.

> SYMPTOMS INCLUDE > Nonspecific but common symptoms of metabolic illnesses include the following: > PDHA is one of the most common genetic disorders that cause abnormalities in the mitochondrial metabolism. Mitochondria are the organelles inside of cells that are reponsible for the production of energy and respiration. The TCA cycle is one of the most important processes in the mitochondria. The TCA cycle produces the majority of the ATP or "chemical energy" necessary for homeostasis. The production of this particular ATP is accomplished by converting molecules of the pyruvate into carbon dioxide, water and energy. After blood sugar molecules have been broken down into two pyruvate molecules, one of two things will occur: if energy is required by the cell then the molecules will be broken down into ATP, carbon dioxide, and water. If there is no need for energy in the cell, then the pyruvate molecules will be formed back together to make a new glucose molecule. These transformations of pyruvate are accomplished primarily by two enzymes, one is pyruvate carboxylase and the other is pyruvate dehydrogenase or PDH. Pyruvavate Carboxylase is an enzyme that converts the pyruvate molecules into oxaloacetate molecules in preparation to reform glucose molecules. PDH is an enzyme that starts the breakdown of pyruvate into the later products of ATP, water and carbon dioxide. In order for pyruvate to breakdown, PDH needs some help from two other enzymes, dihydrolipoyl transacetylase and dihydrolipoyl dehydrogenase. Those three enzymes and these five coenzymes: CoA, NAD+, FAD+, lipoic adic, and TPP, which assist these enzymes, are collectively known as the pyruvate dehydrogenase complex (PDH complex).
 * Gender differences appear for dysfunction of the E1 alpha enzyme subunit, which is coded by the X chromosome. Heterozygous females can manifest severe symptoms, though males are typically affected to a much greater extent.
 * West syndrome is more common in females with PDCD.
 * Severe lactic acidosis with early demise and Leigh syndrome are more commonly observed in males with PDCD.
 * Progressive neurological degeneration is observed more commonly in females with PDCD.
 * Poor feeding
 * Lethargy
 * Rapid breathing (ie, tachypnea)
 * Developmental nonspecific signs of metabolic disease include the following:
 * Mental delays
 * Psychomotor delays
 * Growth retardation
 * Progressive neurologic symptoms of pyruvate dehydrogenase complex deficiency (PDCD) usually start in infancy but may be evident at birth or in later childhood. The following are signs of poor neurological development or degenerative lesions:
 * Poor acquisition or loss of motor milestones
 * Poor muscle tone
 * New onset seizures
 * Periods of incoordination (ie, ataxia)
 * Abnormal eye movements
 * Poor response to visual stimuli
 * Episodic dystonia: This is associated with a deficiency of the E2 subunit, whereas progressive dystonia appears to be associated with a deficiency in the E1-alpha subunit.
 * Early childhood-onset PDCD typically presents with intermittent periods of incoordination, especially during mild illnesses.
 * The following respiratory symptoms are consistent with neurological disease and severe lactic acidosis:
 * Apnea
 * Dyspnea
 * Respiratory depression
 * An acute form resembling Guillain-Barre Syndrome with limb weakness has recently been described.

> This diagram shows a simplified version of the citric acid cycle and shows the enzyme deficit. The dashed line indicates the blocked pathway and the size of the arrows indicates the relative flow of products. Because pyruvate does not proceed to acetyl-coenzyme A (CoA), it is shunted to other pathways that produce lactic acid and alanine.

Citing: WebMD. "Pyruvate Dehydrogenase Deficiency." __Opposing Viewpoints Resource Center__. > 23 Sept. 2007. Gale. CASHS Lib, Chambersburg PA. 31 Mar. 2009 > []. > [] > > Healthline. "Pyruvate dehydrogenase complex defiency." __Opposing Viewpoints__ > __Resource Center__. 2002. Gale. CASHS Lib, Chambersburg PA. 3 Apr. 2009 > []. > []

eMedicine. "Pyruvate Dehydrogenase Complex Deficiency." Updated: Dec 11, 2007 Visited: April 8, 2009 []
 * Author: Richard E Frye, MD, PhD,** Assistant Professor, Departments of Pediatrics and Neurology, University of Texas Health Science Center at Houston