This study seeks to determine if the administration of oral uridine to patients with classical galactosemia, at a dosage of 150 mg/kg/day, as an adjunct to treatment with conventional lactose restriction, will improve the long term outcome and biochemical alterations seen in this disorder. Two groups of patients will be treated between 3 and 13 years of age. Forty patients will be matched by age and sex and one subject from each pair will be randomly assigned to the treatment or placebo group. In addition, 10 children under one year of age will be treated with oral uridine as soon after birth as possible. To assess whether uridine treatment improves neuropsychologic, neurologic,communicative and ovarian function, specific tests able to delineate subtle change in these areas will be serially performed over the 5 year study period. Erythrocyte uridine diphosphate galactose (UDPGal) will be followed to insure that uridine therapy improves UDPGal production. Erythrocyte galactose-1-phosphate (Gal 1-P) will be measured and it is anticipated that uridine will not increase Gal-1-P levels. Biochemical studies will be performed to determine the activities of UDPGal and uridine diphosphate glucose pyrophosphorylase(s) and to differentiate through which intermediates UDPGal is increased in response to uridine intervention. Specific galactolipid and galactoprotein compounds will be analyzed to determine how UDPGal deficiency and uridine treatment affect the synthesis of complex galactose containing macromolecules. Specific galactose-1-phosphate uridyltransferase gene mutations will be determined and correlated with the clinical and biochemical response to uridine treatment.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD026401-05
Application #
2199923
Study Section
Special Emphasis Panel (SRC (NU))
Project Start
1990-02-01
Project End
1995-01-31
Budget Start
1994-02-01
Budget End
1995-01-31
Support Year
5
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Children's Hospital of Los Angeles
Department
Type
DUNS #
094878337
City
Los Angeles
State
CA
Country
United States
Zip Code
90027
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Kaufman, F R; Horton, E J; Gott, P et al. (1995) Abnormal somatosensory evoked potentials in patients with classic galactosemia: correlation with neurologic outcome. J Child Neurol 10:32-6
Xu, Y K; Kaufman, F R; Donnell, G N et al. (1995) HPLC analysis of uridine diphosphate sugars: decreased concentrations of uridine diphosphate galactose in erythrocytes and cultured skin fibroblasts from classical galactosemia patients. Clin Chim Acta 240:21-33
Kaufman, F R; McBride-Chang, C; Manis, F R et al. (1995) Cognitive functioning, neurologic status and brain imaging in classical galactosemia. Eur J Pediatr 154:S2-5
Xu, Y K; Kaufman, F R; Donnell, G N et al. (1995) Radiochemical assay of minute quantities of galactose-1-phosphate uridyltransferase activity in erythrocytes and leukocytes of galactosemia patients. Clin Chim Acta 235:125-36
Ng, W G; Xu, Y K; Kaufman, F R et al. (1994) Biochemical and molecular studies of 132 patients with galactosemia. Hum Genet 94:359-63
Kaufman, F R; Reichardt, J K; Ng, W G et al. (1994) Correlation of cognitive, neurologic, and ovarian outcome with the Q188R mutation of the galactose-1-phosphate uridyltransferase gene. J Pediatr 125:225-7
Kaufman, F R; Loro, M L; Azen, C et al. (1993) Effect of hypogonadism and deficient calcium intake on bone density in patients with galactosemia. J Pediatr 123:365-70
Kaufman, F R; Devgan, S; Donnell, G N (1993) Results of a survey of carrier women for the galactosemia gene. Fertil Steril 60:727-8