Novel mutation (Gly280Ala) in the ATP-binding domain of glycerol kinase causes severe hyperglycerolemia.
Glycerol kinase deficiency is a rarely diagnosed X-linked recessive disorder which occurs as a complex form together with the adrenal hypoplasia congenita (AHC) or with Duchenne muscular dystrophy (DMD) or as an isolated form either symptomatic or asymptomatic. We report the case of a male adult who had pseudo-hypertriglyceridemia (falsely elevated triglycerides of 552 mg/dl) refractory to lipid-lowering therapy for more than 15 years. Further investigations revealed an isolated, asymptomatic glycerol kinase deficiency. Using polymerase chain reaction and direct DNA sequencing, a novel missense mutation Gly280Ala in the Xp21.3 glycerol kinase gene was found. Comparison between human and E.coli glycerol kinase showed that the mutation affects a highly conserved amino acid in an ATP-binding domain in the active centre. This mutation is assumed to destabilize a hydrogen bond between ligand and enzyme resulting in a reduced activity of glycerol kinase and therefore in hyperglycerolemia.
Wibmer
T
T
Physiological Chemistry, Adolf Butenandt Institute, University of Munich, Germany.
Otto
J
J
Parhofer
K G
KG
Otto
C
C
D000368:Aged; D000595:Amino Acid Sequence; D002239:Carbohydrate Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D017809:Fatal Outcome; D005260:Female; D005990:Glycerol / Q000097:blood*; D005991:Glycerol Kinase / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D016133:Polymerase Chain Reaction; D016415:Sequence Alignment; D014280:Triglycerides / Q000097:blood
D014280:Triglycerides; D004247:DNA; D005991:Glycerol Kinase; D005990:Glycerol