What are the genetic changes related to phosphoglycerate dehydrogenase deficiency ?
Mutations in the PHGDH gene cause phosphoglycerate dehydrogenase deficiency. The PHGDH gene provides instructions for making the parts (subunits) that make up the phosphoglycerate dehydrogenase enzyme. Four PHGDH subunits combine to form the enzyme. This enzyme is involved in the production of the protein building block (amino acid) serine. Specifically, the enzyme converts a substance called 3-phosphoglycerate to 3-phosphohydroxypyruvate in the first step in serine production. Serine is necessary for the development and function of the brain and spinal cord (central nervous system). Serine is a part of chemical messengers called neurotransmitters that transmit signals in the nervous system. Proteins that form cell membranes and myelin also contain serine. Serine can be obtained from the diet, but brain cells must produce their own serine because dietary serine cannot cross the protective barrier that allows only certain substances to pass between blood vessels and the brain (the blood-brain barrier).  PHGDH gene mutations result in the production of an enzyme with decreased function. As a result, less 3-phosphoglycerate is converted into 3-phosphohydroxypyruvate than normal and serine production is stalled at the first step. The lack of serine likely prevents the production of proteins and neurotransmitters in the brain and impairs the formation of normal cells and myelin. These disruptions in normal brain development lead to the signs and symptoms of phosphoglycerate dehydrogenase deficiency.