Glycerol kinase deficiency

Glycerol kinase deficiency (GKD), also known as hyperglycerolemia, is a rare X-linked metabolic disorder caused by mutations or deletions in the GK gene located on chromosome Xp21.2. Glycerol kinase is an enzyme that catalyzes the phosphorylation of glycerol to glycerol-3-phosphate, a key step in fat metabolism and gluconeogenesis. Deficiency of this enzyme leads to accumulation of glycerol in the blood (hyperglycerolemia) and urine (glyceroluria). The condition predominantly affects males. GKD presents in several clinical forms. The infantile (or complex) form often results from a contiguous gene deletion syndrome involving the GK gene along with neighboring genes, including the DAX1 gene (causing adrenal hypoplasia congenita) and the dystrophin gene (causing Duchenne muscular dystrophy). Patients with this complex form may present with adrenal insufficiency, which can be life-threatening in the neonatal period, along with progressive muscular dystrophy, developmental delay, and intellectual disability. The juvenile form typically presents with developmental delay, behavioral issues, and metabolic acidosis. The benign or adult form may be asymptomatic and is often discovered incidentally through elevated triglyceride readings on laboratory testing (pseudohypertriglyceridemia), as glycerol is measured in some triglyceride assays. Treatment is primarily supportive and depends on the clinical form. Patients with the complex form require glucocorticoid and mineralocorticoid replacement therapy for adrenal insufficiency, and management of muscular dystrophy follows standard protocols. Dietary management with a low-fat diet may be recommended. Metabolic crises, including hypoglycemia and metabolic acidosis, require prompt medical intervention. Genetic counseling is important for affected families. Prognosis varies significantly depending on the form of the disease, with the isolated benign form having an excellent outlook and the complex form carrying more significant morbidity.

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