The rate of endogenous galactose synthesis in classic galactosemic patients, whom we define as those subjects who convert less than 1% of a [1-13C]galactose bolus to 13CO2 in 1 hour, determines the biochemical phenotype and, thus correlates with the rates of galactitol and galactonate production. We hypothesize that the endogenous synthesis of galactose is developmentally programmed in man and the rate of synthesis in galactosemic patients may be different than in control subjects. We propose to determine the endogenous galactose production rate and its variability in an expanded number of Q188R/Q188R and other galactosemic patients, who convert less than 1% of a [1-13C]galactose bolus to 13CO2 in an hour, and correlate the rate of galactose synthesis with urinary galactitol and galactonate excretion. We will determine whether the endogenous production rate of galactose follows a """"""""""""""""developmental pattern"""""""""""""""", i.e. the rate in infants > children > adults; the magnitude, therefore, being temporarily related to a window of time when the toxicity of galactose may be at its peak in GALT deficiency. In addition, we will determine whether the rate of synthesis is different in galactosemic compared to control subjects.
The second aim i s to determine whether rare atypical galactosemic patients without evidence of learning problems, speech defects and/or hypogonadism, have an atypical residual hepatic galactose oxidative capacity as assessed by breath testing and acute conversion of [13C]galactose to [13C]glucose or possess an atypical alternate pathway activity or an atypical endogenous galactose production rate.
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