Phosphoglycerate dehydrogenase deficiency
Phosphoglycerate dehydrogenase deficiency is a rare metabolic condition characterized by microcephaly, psychomotor retardation, and recurrent seizures.
Overview
Phosphoglycerate dehydrogenase deficiency is characterized by an unusually small head size (microcephaly), impaired development of physical reactions, movements, and speech (psychomotor retardation), and recurrent seizures (epilepsy). The condition involves a progressive loss of brain tissue, specifically affecting the fatty tissue known as myelin that surrounds nerve cells.
Symptoms
Symptoms vary by the age of onset:
- Infantile form: The most severe and common form, characterized by infantile spasms, difficulty feeding, and failure to achieve developmental milestones.
- Juvenile form: Typically involves epilepsy, mild developmental delay, and intellectual disability.
- Adult form: Very rare; symptoms include mild intellectual disability, difficulty coordinating movements (ataxia), and numbness, tingling, and pain in the limbs (sensory neuropathy).
Causes
The condition is caused by mutations in the PHGDH gene, which provides instructions for making the phosphoglycerate dehydrogenase enzyme. This enzyme is essential for the production of the amino acid serine. Because brain cells must produce their own serine—as dietary serine cannot cross the blood-brain barrier—a deficiency leads to impaired production of neurotransmitters and myelin, disrupting brain development.
Inheritance
This condition is inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell have mutations. The parents of an affected individual each carry one copy of the mutated gene but typically do not show signs of the condition.