Professional Abstract
Objective
(1) To determine if children ages 6 to 12 with Duarte galactosemia (DG) show a greater prevalence of developmental complications compared with sibling controls; (2) To determine if children ages 6 to 12 with DG who drank breast milk or milk-based formula as infants show a greater prevalence of developmental complications compared with children with DG who drank low-galactose formula
Study Design
| Design Elements |
Description |
| Design |
Observational: case-control study |
| Population |
206 children ages 6–12 with DG and 144 sibling controls |
Interventions/
Comparators |
Not applicable |
| Outcomes |
Prevalence of developmental complications, including problems with cognition, social skills/behavior, physical development, motor development, and speech and hearing |
| Timeframe |
Immediate follow-up for study outcomes |
DG is caused by partial deficiency of galactose-1-phosphate uridylyltransferase (GALT), an enzyme that converts galactose-1-phosphate to UDP-galactose. DG is a variant of classic galactosemia, which is caused by a complete GALT deficiency and requires careful restriction of high-galactose sources, including breast milk and milk-based formula. Classic galactosemia increases a patient’s risk for long-term developmental complications. In contrast, infants with DG usually thrive while drinking milk, but they accumulate abnormal levels of galactose metabolites during their first year. Two small studies reached conflicting conclusions about whether children with DG are at increased risk for developmental complications. No standard of care exists for whether galactose sources should be restricted in infants with DG.
This observational case-control study compared developmental complications among children with DG with sibling controls and among children with DG who drank milk with children who drank low-galactose formula. Parents or guardians of children ages 6 to 12 with DG completed a survey about their children’s health and diet, including exposure to breast milk or milk-based formula during infancy and whether the children received any developmental interventions before age three. The survey also asked if other children in the family might be eligible for the study. Next, researchers assessed the children for cognition, social skills/behavior, physical and motor development, and speech and hearing. Researchers also collected saliva for genetic testing to confirm DG status.
The study included 206 children ages 6 to 12 with DG from 17 states and Washington, DC, and 144 siblings without DG in the same age range. Of these children, 90% were white, 2% were black, and 5% were another race; 3% were Hispanic. Because of the distribution of the Duarte allele, most children with DG are white. The average age was nine, and 53% were male. Of the children with DG, 40% consumed breast milk or milk-based formula as infants, and 60% consumed low-galactose formula.
Parents of children with DG, physicians, advocacy group representatives, and newborn screening professionals worked with researchers to plan and conduct the study.
Results
Developmental complications did not differ significantly between
- Children with DG and their unaffected siblings
- Children with DG who drank breast milk or milk-based formula during their first year of life and children who drank low-galactose formula
Limitations
Recall bias may have influenced parents’ or guardians’ survey responses about their children’s health and diet as infants. Researchers evaluated only children between the ages of 6 and 12.
Conclusions and Relevance
This study found no association between DG and developmental complications or between breastfeeding or drinking milk-based formula and developmental complications in children with DG.
Future Research Needs
Future research could examine other health outcomes in children with DG and outcomes in children older than the children in this study.
