title: Adrenal dysfunction in glycerol kinase deficiency.
abstract: The infantile form of glycerol kinase deficiency appears to be an X-linked disorder which is consistently characterized by developmental delay and adrenal cortical insufficiency and hypoplasia. We propose that the inherited deficiency of outer mitochondrial membrane-bound glycerol kinase restricts glycerophospholipid synthesis, and, hence, the activation of steroidogenesis. This would limit the conversion of cholesterol to pregnenolone, the precursor for glucocorticoids in the adrenal cortex. The deficiency in cortisol production, with a lack of feedback to the pituitary, would result in increased ACTH production and hypertrophy of the fascicular zone at the same time that replication of the cells within this zone would be inhibited. Similarly, the decreased mineralocorticoid production by the sparse glomerulosal zone would limit the ability of the individual to respond to stress, and would result in development of potentially fatal hyponatremia and hyperkalemia. Organization of the pathway for glycerophospholipid synthesis at the outer mitochondrial membrane would make this pathway particularly vulnerable to mutations disrupting the compartmented production of the parent compound, glycerol 3-phosphate, by mitochondrial-bound glycerol kinase.
authors.forename: W K
authors.initials: WK
authors.lastname: Seltzer
authors.forename: H
authors.initials: H
authors.lastname: Firminger
authors.forename: J
authors.initials: J
authors.lastname: Klein
authors.forename: A
authors.initials: A
authors.lastname: Pike
authors.forename: P
authors.initials: P
authors.lastname: Fennessey
authors.forename: E R
authors.initials: ER
authors.lastname: McCabe
mesh_terms: D000302:Adrenal Cortex / Q000473:pathology; D000311:Adrenal Glands / Q000201:enzymology; D000309:Adrenal Insufficiency / Q000201:enzymology*; D000818:Animals; D002417:Cattle; D002451:Cell Compartmentation; D002648:Child; D002675:Child, Preschool; D008401:Gas Chromatography-Mass Spectrometry; D005991:Glycerol Kinase / Q000172:deficiency*; D006801:Humans; D006854:Hydrocortisone / Q000627:therapeutic use; D008297:Male; D008661:Metabolism, Inborn Errors / Q000201:enzymology*; D008954:Models, Biological; D010085:Oxidative Phosphorylation; D010743:Phospholipids / Q000096:biosynthesis; D010770:Phosphotransferases / Q000172:deficiency*; D013256:Steroids / Q000652:urine; D014018:Tissue Distribution
chemical_list: D010743:Phospholipids; D013256:Steroids; D010770:Phosphotransferases; D005991:Glycerol Kinase; D006854:Hydrocortisone