COMPARISON OF ERYTHROCYTE URIDINE SUGAR NUCLEOTIDE LEVELS IN NORMALS, CLASSIC GALACTOSEMICS, AND PATIENTS WITH OTHER METABOLIC DISORDERS

By limiting galactosylation mechanisms, a cellular deficiency of the uridine sugar nucleotide, UDPgalactose, has been implicated as a cause of the long term complications seen in patients with classic galactosemia despite dietary treatment. As a result, great interest has been generated in the accurate assessment of UDPgalactose, as well as UDPglucose, from which UDPgalactose may be derived by the function of a ubiquitous, active UDPgalactose-4-epimerase. Since several series of values for the concentration of these compounds in red blood cells (RBCs) of galactosemics have been flawed by the use of methods subsequently shown to be unsuitable, we have quantified erythrocyte UDPgalactose and UDPglucose levels by an accurate high performance liquid chromatography (HPLC) assay in 116 normals, 76 galactosemics, and 39 patients with other metabolic disorders, These large groups have permitted the evaluation of age, diet, and genotype as influential factors in the steady-state RBC levels of the sugar nucleotides. The data show that age is an important determinant of RBC levels, with children younger than 10 years having higher values than individuals older than 10 years. Mean UDPgalactose levels in galactosemic children younger than 10 years and those older than 10 years were 30% and 18% lower, respectively, than levels in comparable normals. Although the mean differences were highly significant, there was considerable overlap of individual values. There was no difference in UDPglucose levels between galactosemics and normals. Diet plays a role in that erythrocytes of children on special metabolic diets low in protein and therefore also low in lactose show significantly lower levels of both UDPgalactose and UDPglucose than normal children, with the average UDPgalactose level similar to that in galactosemics, An analysis of UDPgalactose content with respect to genotype in galactosemics did not show any correlation with homozygosity of the Q188R allele. The average ratio of UDPglucose to UDPgalactose in RBCs of galactosemics under 10 years of age was 62% higher than the ratio in cells of comparable normals, whereas in older galactosemics there was a 29% increase. In 55% of galactosemics, the ratio was more than 2 SD above the mean of the normals, indicating that an increase in the erythrocyte UDPglucose to UDPgalactose ratio is a characteristic of the majority of galactosemic patients. The difference in the ratio, which deviates from the expectation for the equilibrium normally established by UDPgalactose-4-epimerase, implies a perturbation in epimerase function in galactosemic RBCs, the nature of which remains to be determined by examining the functional cellular pools and flux of hexoses not only in erythrocytes but in other model cell systems. Copyright (C) 1995 by W.B. Saunders Company