Galactosemia: Alterations in sulfate metabolism secondary to galactose-1-phosphate uridyltransferase deficiency

Galactosemia, a genetic disease whose symptoms include lens cataracts, is characterized by enzyme deficiencies of galactokinase (GALK) and galactose-1-phosphate uridyltransferase (GALT). The toxic processes producing the pathological conditions of the disease have been investigated in cultured mutant fibroblasts challenged with galactose. Results indicate that GALT-deficient cells incorporate significantly less labeled sulfate, and GALK-deficient cells significantly more, when galactose is substituted for glucose in the medium. GALT-deficient cells accumulate intracellular galactose-1-phosphate and deteriorate in culture after 2-3 weeks. Galactose toxicity appears to cause the decreased sulfate incorporation of GALT-deficient cells. No difference in labeled uridine incorporation was observed. These findings demonstrate that absence of GALT-activity or galactose accumulation produces biochemical alterations in sulfate metabolism. These may be the toxic mechanisms underlying tissue abnormalities in galactosemia.