What is the biochemistry behind the disease?

Pyruvate dehydrogenase complex (PDC) deficiency (PDCD) is one of the most common neurodegenerative disorders associated with abnormal mitochondrial metabolism. The citric acid cycle is a major biochemical process that derives energy from carbohydrates. Malfunction of this cycle deprives the body of energy. An abnormal lactate buildup results in nonspecific symptoms (e.g., severe lethargy, poor feeding, tachypnea), especially during times of illness, stress, or high carbohydrate intake.
                                    
Pyruvate dehydrogenase (PDH) deficiency (PDHD) is caused by a deficiency of one or more enzymes or cofactors(e.g. thiamine) that are needed for an important chemical reaction in the cells of the body. These enzymes or cofactors belong to the pyruvate dehydrogenase complex and is used to convert a chemical named pyruvate to acetyl-coenzyme A (widely known as acetyl-CoA). Acetyl-CoA is an important chemical which the body requires to make citrate for the cells. Without the enzyme or cofactor, pyruvate cannot be converted to acetyl-CoA. As such, there will be too much pyruvate in the cells. The absence of enzymes will cause reaction of pyruvate to be directed to production of lactate.Citrate is the first step in another important group of chemical reactions called the citric acid cycle (also known as Electron Transport Chain(ETC)), which then cannot proceed. The body tries to make alternate pathways to produce more acetyl-CoA, but there is still not enough energy made in the body, especially in the central nervous system (CNS). The amount of energy that is deficient depends on the amount of the enzyme that is deficient. 

The condition is sometimes referred to as pyruvate dehydrogenase complex (PDHC) deficiency because there is a "complex" of three enzymes normally used in the reaction; when any one or more of the enzymes needed for the above-described reaction are deficient, the condition results. Glucose in the body will be converted into pyruvate. In a healthy human, pyruvate can be converted into Acetyl-CoA, which is used in the ETC, and lactate. Conversion to Acetyl-CoA is more favoured and will happen more than it being converted to lactate. However, people who suffers from PDHD lacks the pyruvate dehydrogenase complex, hence are unable to metabolise pyruvate to Acetyl-CoA, and can only convert pyruvate to lactate, also known as lactic acid. Lactic acid in high concentration in the body is harmful as it causes lactic acidosis which is life-threatening as it might cause shock and organ failures.
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