IN-VIVO OXIDATION OF [C-13]GALACTOSE IN PATIENTS WITH GALACTOSE-1-PHOSPHATE URIDYLTRANSFERASE DEFICIENCY

We developed an intravenous and oral [C-13]galactose breath test for t he in vivo study of galactose metabolism. Following an intravenous bol us of 7 mg/kg of [1-C-13]galactose in the fasting state, normal childr en and adults eliminated 3-6% and 21-47% of the bolus as (CO2)-C-13 in expired air collected over 1 and 5 h, respectively, Comparable fracti onal elimination was seen when the dose was given orally. Patients wit h galactosemia who have barely detectable or absent galactose-l-phosph ate uridyltransferase (GALT) activity in erythrocytes and are homoalle lic for the Q188R gene mutation, when given a 7 mg/kg intravenous bolu s had barely detectable (CO2)-C-13 in air samples in the first hour, b ut eventually eliminated as much as 3.6% of the dose in 5 h. A galacto semia/Duarte (Q188R/N314D) compound heterozygote and a homozygous Duar te subject, as well as a subject with one normal allele and one Q188R allele, showed normal in vivo oxidation. An assessment of whole body g alactose metabolism can be made with this procedure. Further use of th is in vivo modality in patients with different genetic backgrounds sho uld increase our understanding of genotype-phenotype relationships in hereditary galactosemia. (C) 1995 Academic Press, Inc.