Monitoring of biochemical status in children with Duarte galactosemia: utility of galactose, galactitol, galactonate, and galactose 1-phosphate.

BACKGROUND: Duarte galactosemia (DG) is frequently detected in newborn-screening programs. DG patients do not manifest the symptoms of classic galactosemia, but whether they require dietary galactose restriction is controversial. We sought to assess the relationships of selected galactose metabolites (plasma galactose, plasma galactitol, erythrocyte (RBC) galactitol, RBC galactonate, and urine galactitol and galactonate) to RBC galactose 1-phosphate (Gal-1-P), dietary galactose intake, and neurodevelopmental/clinical outcomes in DG children. METHODS: We studied 30 children 1-6 years of age who had DG galactosemia and were on a regular diet. All participants underwent a physical and ophthalmologic examination and a neurodevelopmental assessment. RBC galactitol, RBC galactonate, RBC Gal-1-P, plasma galactose, plasma galactonate, and urine galactitol and galactonate concentrations were measured. RESULTS: RBC galactitol and galactonate concentrations were about 2 and 6 times higher, respectively, than control values. Plasma galactose and galactitol concentrations were also about twice the control values. The mean values for RBC Gal-1-P and urine galactitol were within the reference interval. We found a relationship between plasma and urine galactitol concentrations but no relationship between RBC galactose metabolites and urine galactitol. There was a significant relationship between galactose intake and RBC galactose metabolites, especially RBC galactitol (P < 0.0005) and RBC galactonate (P < 0.0005). Galactose intake was not related to the urine galactitol, plasma galactose, or plasma galactitol concentration. RBC galactitol, RBC galactonate, plasma galactose, plasma galactitol, and urine galactonate concentrations showed no relationship with clinical or developmental outcomes. CONCLUSIONS: DG children on a regular diet have RBC Gal-1-P concentrations within the reference interval but increased concentrations of other galactose metabolites, including RBC galactitol and RBC galactonate. These increased concentrations correlate with galactose intake and neither cause any developmental or clinical pathology during early childhood nor oblige a lactose-restricted diet.

The effect of dietary fruits and vegetables on urinary galactitol excretion in galactose-1-phosphate uridyltransferase deficiency.

Even on a lactose-restricted diet, urinary galactitol excretion and erythrocyte galactose-1-phosphate levels are persistently elevated in patients with galactose-1-phosphate uridyltransferase deficiency. In order to determine the contribution of galactose in dietary fruits and vegetables to this phenomenon, (1) the content of galactose in a lactose-free diet was directly measured when a galactosaemic patient's diet was specifically enriched in those fruits and vegetables which contain relatively large amounts of free galactose and (2) galactitol excretion was determined during ingestion of this diet for 3 weeks and while on a synthetic diet for 1 week that provided < 8 mg galactose/day. For comparison the effect of a 3-week supplementation of 200 mg galactose/day was determined. The measured intake in total foodstuffs matched the theoretical content of galactose in the patient's diet based on amounts in fruits and vegetables alone, thus supporting the concept that fruits and vegetables are primarily responsible for galactose intake in a lactose-free diet. All of the dietary manipulations, however, had relatively little effect on metabolite levels, suggesting that endogenous galactose production is primarily responsible for the elevated levels of galactose metabolites routinely detected in patients on lactose-restricted diets.