Plasma galactose and galactitol concentration in patients with galactose-1-phosphate uridyltransferase deficiency galactosemia: Determination by gas chromatography /mass spectrometry

The plasma concentration of galactose and galactitol was measured in 27 pat ients with galactose-l-phosphate uridyltransferase (GALT) deficiency galact osemia on a lactose-restricted diet, 17 infants on lactose-free formula, an d 21 infants and children on a normal diet, by a newly devised isotope dilu tion gas chromatograph/mass spectrometry (GC/MS) method, The method was lin ear in the range of 0.1 to 10 mu mol/L for galactose and 1 to 20 mu mol/L f or galactitol with good reproducibility and a coefficient of variation less than 3%. The mean plasma galactose in 15 patients who were homozygous for the most common Q188R mutation of the GALT gene was 2.72 +/- 0.70 mu mol/l (mean +/- SE) with a range of 0.58 to 3.98 in specimens obtained at regular clinic visits, In 12 patients with other GALT mutations, it was 2.45 +/- 0 .75 mu mol/L. The mean value in nongalactosemic subjects on lactose-free fo rmula was 0.52 +/- 0.08 mu mol/l with a range of 0.12 to 1.25, The range in 21 normal subjects without diet restriction was 0.11 to 6.33 mu mol/L, wit h a mean of 1.48 +/- 0.32, The plasma galactitol level was 11.63 +/- 0.46 a nd 10.85 +/- 1.38 mu mol/L in the 2 galactosemic groups, There was no relat ionship between plasma galactose and galactitol levels, with variable ratio s of the two substances in the galactosemic patients. Galactitol was not de tectable in the plasma of normal subjects. The red blood cell galactose-1-p hosphate level was also measured in the galactosemic patients, and no relat ionship between plasma galactose and red blood cell galactose-1-phosphate w as found, The galactose-1-phosphate concentration was 28 to 54 times higher than the ambient galactose. The low galactose concentration in the plasma of galactosemics on galactose-restricted diets in relation to the higher pl asma galactitol and red blood cell galactase-1-phosphate is a metabolic eni gma. The ability to measure plasma galactose accurately presents a new way of characterizing the galactosemic patient and the levels monitored over ti me may provide insight into the development of long-term complications asso ciated with the disorder. Copyright (C) 2000 by W.B. Saunders Company.