SNP Shot: Genomic Insights

Phosphoglycerate dehydrogenase deficiency (PGDHD) is a condition characterized by a small head size (microcephaly), delayed development of movement, speech, and physical reactions (psychomotor retardation), and recurring seizures (epilepsy). The severity and age of onset vary among different types of PGDHD. The most common and severe form is the infantile type, which starts in infancy. Juvenile and adult types are much rarer, with symptoms appearing later in life.

PGDHD causes a gradual loss of brain cells, leading to brain atrophy. This particularly affects the myelin, which is the fatty tissue protecting nerve cells (hypomyelination). Often, the corpus callosum, which connects the two brain hemispheres, is underdeveloped, and the brain's ventricles (fluid-filled spaces) are enlarged. Disrupted brain development results in progressive microcephaly, where the head appears to shrink as the body grows. This poor brain growth hinders the achievement of developmental milestones such as sitting and speaking, and many infants struggle with feeding.

Seizures in PGDHD can take different forms. Infantile spasms (recurrent muscle contractions) are common early on. If untreated, seizures may progress to tonic-clonic seizures (loss of consciousness, muscle rigidity, and convulsions), myoclonic seizures (rapid muscle jerks), or drop attacks (sudden loss of muscle tone).

The infantile form of PGDHD presents with many of the features mentioned. Those with the juvenile form usually experience epilepsy, mild developmental delay, and intellectual disability. Only one case of the adult form has been documented, with symptoms starting in mid-adulthood, including mild intellectual disability, coordination problems (ataxia), and sensory neuropathy (numbness, tingling, and pain in the limbs).

Inheritance:

PGDHD follows an autosomal recessive inheritance pattern. This means that an individual must inherit a mutated copy of the gene from both parents to develop the condition. The parents, who each carry one copy of the mutated gene, typically do not show any symptoms.