LOW EFFICIENCY OF [C-14] GALACTOSE INCORPORATION BY GALACTOSEMIC SKINFIBROBLASTS - RELATIONSHIP WITH NEUROLOGICAL SEQUELAE

The incorporation of radioactivity from [1-C-14]galactose into TCA-pre cipitable material was determined in skin fibroblasts derived from 11 galactosemic patients deficient in galactose 1-phosphate uridyl transf erase (GALT-). ''R'' ratios (designated the R phenotype) were defined as the ratio between [C-14]galactose incorporation and [H-3]leucine in corporation. Results were expressed as a percentage of the controls. I n the GALT-strains this ratio varied from strain to strain, presumably depending on the efficiency of the secondary route via the UDP-galact ose pyrophosphorylase pathway. In 10 GALT-patients without late seriou s clinical manifestations, the R phenotype varied hom 37 to 57% of the control value. In the 11th patient, the R phenotype was only 20% of t he control. Thus, we obtained a significantly lower R phenotype in one patient who was distinguished from the others by having very severe d elayed neurological complications, although compliance to galactose-fr ee diet was good. We suggest that, in this patient, the development of the UDP-galactose pyrophosphorylase pathway was not sufficient to ens ure the availability of enough galactose for the necessary synthesis o f glycoproteins and glycolipids. Thus the R phenotype may be an indica tor 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 co mplications are required to confirm this relationship. (C) 1994 Academ ic Press, Inc.