Exp Clin Endocrinol Diabetes 2005; 113(7): 396-403
DOI: 10.1055/s-2005-865723
Article

J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Novel Mutation (Gly280Ala) in the ATP-Binding Domain of Glycerol Kinase Causes Severe Hyperglycerolemia

T. Wibmer1 , 2 , J. Otto1 , 3 , K. G. Parhofer2 , C. Otto2
  • 1Physiological Chemistry, Adolf Butenandt Institute, University of Munich, Germany
  • 2Medical Department 2 - Großhadern, University Hospital Munich, Germany
  • 3deceased
Further Information

Publication History

Received: August 12, 2004 First decision: October 22, 2004

Accepted: April 13, 2005

Publication Date:
18 July 2005 (online)

Abstract

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.

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M.D. Carsten Otto

Medical Department 2 - Großhadern
University Hospital of Munich

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Email: carsten.otto@med.uni-muenchen.de