Decreased availability of GDP-L-fucose in a patient with LAD II with normal GDP-D-mannose dehydratase and FX protein activities

J Leukoc Biol. 1999 Jul;66(1):95-8. doi: 10.1002/jlb.66.1.95.

Abstract

Leukocyte adhesion deficiency type II (LAD II) is caused by a disorder in the metabolism of GDP-L-fucose, which causes hypofucosylation of glycoconjugates. This study analyzes a newly identified LAD II patient who shows the same severe hypofucosylation of glycoconjugates as the other described patients. However, in vitro assays of cytosolic extracts from leukocytes and fibroblasts of the patient demonstrated a normal GDP-L-fucose biosynthesis from GDP-D-mannose. Analysis of the two enzymes involved in the pathway, GDP-D-mannose 4,6-dehydratase and FX protein, revealed normal numbers of transcripts without any detectable mutations within the coding regions of either gene. In contrast to previously published observations [Sturla et al. (1998) FEBS Lett. 429, 274-278], the major pathway of GDP-L-fucose synthesis can be normal in LAD II.

MeSH terms

  • Carbohydrate Epimerases*
  • Carbon Radioisotopes
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Extracts
  • Cytosol
  • DNA, Complementary
  • Guanosine Diphosphate Fucose / metabolism*
  • Guanosine Diphosphate Mannose / metabolism
  • Humans
  • Hydro-Lyases / genetics
  • Hydro-Lyases / metabolism*
  • Ketone Oxidoreductases*
  • Leukocyte-Adhesion Deficiency Syndrome / metabolism*

Substances

  • Carbon Radioisotopes
  • Carrier Proteins
  • Cell Extracts
  • DNA, Complementary
  • Guanosine Diphosphate Fucose
  • Guanosine Diphosphate Mannose
  • TSTA3 protein, human
  • Ketone Oxidoreductases
  • Hydro-Lyases
  • GDPmannose 4,6-dehydratase
  • Carbohydrate Epimerases