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 u ridine sugar nucleotide, UDPgalactose, has been implicated as a cause of the long term complications seen in patients with classic galactose mia despite dietary treatment. As a result, great interest has been ge nerated in the accurate assessment of UDPgalactose, as well as UDPgluc ose, from which UDPgalactose may be derived by the function of a ubiqu itous, 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 sho wn to be unsuitable, we have quantified erythrocyte UDPgalactose and U DPglucose levels by an accurate high performance liquid chromatography (HPLC) assay in 116 normals, 76 galactosemics, and 39 patients with o ther metabolic disorders, These large groups have permitted the evalua tion of age, diet, and genotype as influential factors in the steady-s tate RBC levels of the sugar nucleotides. The data show that age is an important determinant of RBC levels, with children younger than 10 ye ars having higher values than individuals older than 10 years. Mean UD Pgalactose levels in galactosemic children younger than 10 years and t hose older than 10 years were 30% and 18% lower, respectively, than le vels in comparable normals. Although the mean differences were highly significant, there was considerable overlap of individual values. Ther e was no difference in UDPglucose levels between galactosemics and nor mals. Diet plays a role in that erythrocytes of children on special me tabolic diets low in protein and therefore also low in lactose show si gnificantly lower levels of both UDPgalactose and UDPglucose than norm al children, with the average UDPgalactose level similar to that in ga lactosemics, An analysis of UDPgalactose content with respect to genot ype 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 ra tio in cells of comparable normals, whereas in older galactosemics the re was a 29% increase. In 55% of galactosemics, the ratio was more tha n 2 SD above the mean of the normals, indicating that an increase in t he erythrocyte UDPglucose to UDPgalactose ratio is a characteristic of the majority of galactosemic patients. The difference in the ratio, w hich deviates from the expectation for the equilibrium normally establ ished by UDPgalactose-4-epimerase, implies a perturbation in epimerase function in galactosemic RBCs, the nature of which remains to be dete rmined 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