title: Low efficiency of [14C]galactose incorporation by galactosemic skin fibroblasts: relationship with neurological sequelae.
abstract: The incorporation of radioactivity from [1-14C]-galactose into TCA-precipitable material was determined in skin fibroblasts derived from 11 galactosemic patients deficient in galactose 1-phosphate uridyl transferase (GALT-). "R" ratios (designated the R phenotype) were defined as the ratio between [14C]galactose incorporation and [3H]leucine incorporation. Results were expressed as a percentage of the controls. In the GALT-strains this ratio varied from strain to strain, presumably depending on the efficiency of the secondary route via the UDP-galactose pyrophosphorylase pathway. In 10 GALT-patients without late serious clinical manifestations, the R phenotype varied from 37 to 57% of the control value. In the 11th patient, the R phenotype was only 20% of the control. Thus, we obtained a significantly lower R phenotype in one patient who was distinguished from the others by having very severe delayed neurological complications, although compliance to galactose-free diet was good. We suggest that, in this patient, the development of the UDP-galactose pyrophosphorylase pathway was not sufficient to ensure the availability of enough galactose for the necessary synthesis of glycoproteins and glycolipids. Thus the R phenotype may be an indicator of the risk of late neurological complications. The determination of the R phenotype of GALT-patients may therefore be valuable. However, further investigations of galactosemic patients with neurological complications are required to confirm this relationship.
authors.affiliation: INSERM U56, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France.
authors.forename: N
authors.initials: N
authors.lastname: Kadhom
authors.forename: J
authors.initials: J
authors.lastname: Baptista
authors.forename: M
authors.initials: M
authors.lastname: Brivet
authors.forename: C
authors.initials: C
authors.lastname: Wolfrom
authors.forename: M
authors.initials: M
authors.lastname: Gautier
mesh_terms: D000293:Adolescent; D002478:Cells, Cultured; D002648:Child; D005347:Fibroblasts / Q000378:metabolism; D005690:Galactose / Q000378:metabolism*; D005693:Galactosemias / Q000150:complications / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007930:Leucine / Q000378:metabolism; D009422:Nervous System Diseases / Q000209:etiology*; D010641:Phenotype; D012867:Skin / Q000166:cytology; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase / Q000172:deficiency
chemical_list: D005694:UTP-Hexose-1-Phosphate Uridylyltransferase; D007930:Leucine; D005690:Galactose