Biochemical monitoring of treatment for galactosaemia: Biological variability in metabolite concentrations

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Abstract
Red cell galactose 1‐phosphate (Gal‐1‐P) concentrations and urinary galactitol excretion have been suggested as biochemical indices of dietary compliance in classical transferase‐deficient galactosaemia. We report our experience of measuring both in 32 patients over 0–10.9 years (median 3.45). A total of 438 blood specimens for Gal‐1‐P and 383 urine specimens for galactitol assay were received; 317 pairs of specimens were collected at the same time. Concentrations of both analytes fell rapidly over the first 2–3 months following dietary intervention, to mean (geometric SD) levels of 225 (1.60) μmol/L red cells for Gal‐1‐P and 388 (1.19) μmol/mmol creatinine for galactitol. Concentrations then fell exponentially over the next 7–8 years, with times to half‐disappearance of 6.3 years for Gal‐1‐P and 6.4 years for galactitol, to levels of 104 (1.58) and 193 (1.36) respectively in patients aged over 10 years. Concentrations of both analytes were independent of the presence of the common Q188R mutation. Mean intra‐ and inter‐individual coefficients of variation (CV) across the range of values studied were 36% and 61% for Gal‐1‐P, and 37% and 42% for galactitol. Analytical CVs were 3.6% for Gal‐1‐P and 5.5% for galactitol, indicating that the major source of variability is biological. The correlation coefficient between Gal‐1‐P and galactitol in paired samples overall was 0.33; the regression equation being [Galactitol] = 0.84[Gal‐1‐P]+176. Serial measurements of both Gal‐1‐P and galactitol may be valuable in monitoring galactosaemia, but high intra‐individual biological variability limits their usefulness. Standardization of sample collection times may improve this. Further work is needed to assess the predictive values of both analytes for long‐term outcome.