Human glycerol kinase deficiency: an inborn error of compartmental metabolism.

Twelve individuals have been described with glycerol kinase deficiency. Five of these individuals are adults who were noted incidentally to have pseudohypertriglyceridemia. Six of these individuals are children who manifest a clinical complex which includes adrenal hypoplasia/insufficiency and developmental delay. Another child has intermittent coma, a normal IQ, and no evidence of adrenal insufficiency. Genetic and biochemical hypotheses are proposed to explain this clinical variability. Glycerol kinase binds specifically and reversibly to the porin, the pore-forming protein of the outer mitochondrial membrane, which also binds hexokinase. Mutations affecting any component of this kinase-binding system will alter the properties of this system. Glycerol kinase deficiency, as an inborn error of this compartmented metabolic system, offers an investigational opportunity for studying this microenvironment.