Disorder of plasmalogens biosynthesis

Disorders of plasmalogen biosynthesis, also known as plasmalogen deficiency or plasmalogen synthesis defects, are a group of rare inherited metabolic conditions in which the body cannot properly produce plasmalogens — a specialized class of ether phospholipids that are critical components of cell membranes, particularly abundant in the brain, heart, lungs, and kidneys. Plasmalogens play important roles in membrane structure, antioxidant defense, and cellular signaling. The most well-characterized disorders of plasmalogen biosynthesis are the rhizomelic chondrodysplasia punctata (RCDP) spectrum, caused by defects in peroxisomal enzymes involved in the plasmalogen synthesis pathway, including GNPAT (dihydroxyacetone phosphate acyltransferase), AGPS (alkyldihydroxyacetone phosphate synthase), and PEX7 (peroxisomal biogenesis factor 7). Clinical features typically manifest at birth or in early infancy and may include severe skeletal abnormalities such as rhizomelic (proximal) limb shortening, stippled calcifications of cartilage (chondrodysplasia punctata), cataracts, profound intellectual disability, growth failure, seizures, and ichthyosis (dry, scaly skin). The severity of the condition varies depending on the specific genetic defect and the degree of residual plasmalogen synthesis. Many affected individuals have a significantly shortened lifespan, with severe forms often leading to death in infancy or early childhood, though milder phenotypes with longer survival have been described. Currently, there is no curative treatment for disorders of plasmalogen biosynthesis. Management is supportive and multidisciplinary, focusing on nutritional support, physical therapy, orthopedic interventions for skeletal complications, ophthalmologic care for cataracts, and seizure management. Research into plasmalogen replacement therapy and other experimental approaches is ongoing but remains in early stages. Genetic counseling is recommended for affected families.

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