Mucolipidosis IV fibroblasts synthesize normal amounts of hyaluronic acid.
Mucolipidosis IV (ML IV) (McKusick 252650) is an autosomal recessive metabolic disorder that displays signs of both lipid and mucopolysaccharide (glycosaminoglycan) storage. It has been reported that fibroblasts from ML IV patients exhibit abnormally high synthesis of hyaluronic acid in culture. In our search for a biochemical marker that will enable positive identification of ML IV, we studied glycosaminoglycan synthesis in fibroblast cultures from patients with this disease. ML IV and normal control fibroblasts were incubated with [3H]glucosamine and [35S]sulphate. Labelled glycosaminoglycans were extracted from the cell layer and medium. Chondroitin sulphate and hyaluronic acid were determined by analysis of disaccharides after digestion with chondroitinase ABC. Synthesis of neither of these two glycosaminoglycans differed significantly between control and ML IV fibroblasts. Synthesis of hyaluronic acid was nearly linear for 24 h, with mean calculated values of 11.7 +/- 1.4 and 14.4 +/- 1.6 pg/cell per 24 h in control and ML IV cultures respectively. The variability within the two groups is attributed primarily to population variability and possibly to culture density. These experiments exclude the possibility that a general metabolic defect in hyaluronic acid synthesis is responsible for the ML IV phenotype, nor can such a defect be used as a diagnostic tool for the disease.
Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland.
E
E
Goldin
Y
Y
Imai
C R
CR
Kaneski
P G
PG
Pentchev
R O
RO
Brady
V C
VC
Hascall
D000328:Adult; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005347:Fibroblasts / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis; D006801:Humans; D006820:Hyaluronic Acid / Q000096:biosynthesis*; D007223:Infant; D009081:Mucolipidoses / Q000378:metabolism*
D006025:Glycosaminoglycans; D006820:Hyaluronic Acid