Elevated Carbohydrate-Deficient Transferrin (CDT) and Its Normalization on Dietary Treatment as a Useful Biochemical Test for Hereditary Fructose Intolerance and Galactosemia

Abstract

Abnormalities in protein glycosylation are reported in fructosemia (HFI) and galactosemia, although, particularly in HFI, the published data are limited to single cases. The purpose was to investigate the usefulness of the carbohydrate-deficient transferrin (CDT) profile for identification and monitoring of these disorders. First we analyzed CDT values before and shortly after the diagnosis in 10 cases of HFI and 17 cases of galactosemia. In all patients, elevated CDT levels were found that significantly (p Ͻ 0.0001) decreased with the therapeutic diet (27.3 Ϯ 11.5% versus 9.3 Ϯ 5.1% for HFI and 43.8 Ϯ 14.1% versus 11.2 Ϯ 4.0% for galactosemia). To evaluate the use of CDT test in monitoring compliance, the test was performed in 25 HFI patients on fructose-restricted diet. We found an elevated CDT level on 104 from 134 tests (mean 11.3 Ϯ 5.5%, control 1.5%-6.2%). The fructose intake was found to be 90 Ϯ 70 mg/kg/d, and the diet was unbalanced. A number of patients presented lower height, elevated urinary uric acid excretion, and hypercalciuria. In conclusion, abnormal percentage of CDT (%CDT) values may allow prompt detection of HFI (or galactosemia). Persistence of some abnormalities in HFI on treatment may be caused by trace amounts of fructose ingestion and/or a deficient diet. Regular %CDT measurements are suggested for HFI treatment monitoring.

Novel techniques and newer markers for the evaluation of “proximal tubular dysfunction”

“…Accumulation of the ALDOB substrate fructose-1-phosphate causes subsequent depletion of the adenosine triphosphate pool and influences uric acid metabolism. Pronicka et al [40] reported an increase in renal loss of uric acid associated with lower serum uric acid levels in HFI patients, indicating impaired tubular resorption. These authors observed an increase in serum levels of uric acid after fructose loading, suggesting that hyperuricosuria in HFI patients depends on the overproduction of uric acid and its deficient re-uptake as a result of FS.…”

“…These authors observed an increase in serum levels of uric acid after fructose loading, suggesting that hyperuricosuria in HFI patients depends on the overproduction of uric acid and its deficient re-uptake as a result of FS. Since a simple metabolic test is not available, the determination of carbohydrate-deficient transferrin (CDT), recently found to be elevated in most HFI patients [34,40,41], may have diagnostic and monitoring value. However, care should be taken not to misinterpret the abnormal results as congenital disorder of glycosylation [42].…”

Understanding Human Glycosylation Disorders: Biochemistry Leads the Charge

“…There is no explanation for how PGM1 deficiency causes the absence of entire glycan chains from proteins. However, uncontrolled galactosemia that leads to Gal-1-P accumulation (54) and hereditary fructose intolerance and Fru-1-P accumulation produce similar glycosylation abnormalities (55). Intracellular accumulation of various sugar phosphates or other metabolic byproducts appears to prevent full N-glycosylation in selected cells and tissues.…”

Biomarkers and diagnosis of congenital disorders of glycosylation

“…However, in many countries the diagnosis of galactosemia is part of the metabolic screening of newborns, therefore most cases of galactosemia are already excluded when diagnostic testing for CDG is considered. Hereditary fructose intolerance also feigns CDG and must be considered as a differential diagnosis, especially for CDG Ib, with a predominance of hepatogastrointestinal symptoms and hypoglycemia [16,17]. Under regular treatment CDT decreases or normalizes in galactosemia and hereditary fructose intolerance, making CDT a useful therapeutic marker in these disorders [17,18].…”