This project has results

Developmental Outcomes in Children with Duarte Galactosemia

Results Summary and Professional Abstract

Results Summary

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What was the research about?

Galactosemia is a group of rare, inherited health problems. Babies with galactosemia have problems breaking down galactose, a sugar in milk. Babies with the most severe type of galactosemia get sick and may die if they drink breast milk or milk-based formula. Even if they don’t drink milk, they may have developmental complications when they are older. Developmental complications include problems moving, speaking, learning, hearing, or getting along with people.

Duarte galactosemia, or DG, is a less serious type of galactosemia. In DG, babies can break down some but not all of the galactose in milk. Few studies have looked at the risks of DG. Doctors don’t know whether babies with DG can drink breast milk and milk-based formula safely or whether drinking milk will cause problems when these babies are older.

In this study, the research team looked at whether

Children with DG have more developmental complications than their siblings without DG
Children with DG who drank breast milk or milk-based formula when they were babies have more developmental complications than children with DG who drank low-galactose formula

What were the results?

Children with DG didn’t have more developmental complications than their siblings without DG.

Children with DG who drank breast milk or milk-based formula didn’t have more developmental complications than children with DG who drank low-galactose formula.

Who was in the study?

The study included 206 children ages 6 to 12 with DG from 17 states and Washington, DC. Of the children with DG, 40 percent drank breast milk or milk-based formula as babies, and 60 percent drank low-galactose formula. The study also included 144 siblings of these children. The siblings were in the same age range but didn’t have DG. Of all the children, 90 percent were white, 2 percent were black, and 5 percent were another race; 3 percent were Hispanic. Because of the genetics of DG, most children with DG are white. The average age was nine, and 53 percent were boys.

What did the research team do?

The research team asked parents or guardians of children with DG to fill out a survey. The survey asked about

Their children’s health and diet, including whether they drank milk before age one
Special educational help children received before age three
Other children in the family without DG who could be in the study

Next, the research team checked children for developmental complications. The team tested the children’s abilities to move, speak, learn, hear, and get along with people. Team members also did genetic tests to make sure which children did and didn’t have DG.

Parents of children with DG, doctors, and people from advocacy groups worked with the research team on the study.

What were the limits of the study?

Parents or guardians may not have been able to accurately remember their children’s health and diet as babies. Also, results may have differed if the research team had tested children older than 12.

Future research could look at whether children with DG have other kinds of health problems. Researchers could also look at children older than the children in this study.

How can people use the results?

Doctors and parents can use the results when thinking about whether to avoid breast milk and milk-based formula for babies with DG.

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.

Journal Articles

Pediatrics

Developmental Outcomes in Duarte Galactosemia

More on this Project

This project's final research report is expected to be available by August 2020.

Peer-Review Summary

Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.

The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments.

Peer reviewers commented and the researchers made changes or provided responses. Those comments and responses included the following:

The reviewers asked why the researchers did not conduct biochemical assays of enzyme and metabolite levels or strive to correlate the levels of such markers to developmental outcomes. The researchers said they did not do such tests to avoid subjecting children in the study to a needle stick, which the researchers felt was not necessary. They used saliva to collect DNA to confirm the children’s diagnoses. The researchers noted that prior research implies that the children with Duarte galactosemia would all have normal levels of a key metabolite at their ages of 6 to 12, regardless of diet.
The reviewers asked why the report did not discuss dietary exposure to galactose and not correlate galactose exposure to outcomes. The researchers said that they collected galactose exposure as a binary variable based on parent reports of their children’s diet when they were 2 to 12 months old. This enabled the largest number of cases to be available for comparison. However, the researchers noted that if they had seen any evidence of difference in outcomes between children who were exposed or not exposed to galactose, they would have attempted to analyze the issue further. Since no difference was observed, the researchers did not perform any further analysis.

Conflict of Interest Disclosures

View the COI disclosure form.

Project Details

Principal Investigator

Judith L. Fridovich-Keil, PhD

Project Status

Completed; PCORI Public and Professional Abstracts Posted

Project Title

Intervention and Outcomes in Duarte Galactosemia

Board Approval Date

April 2015

Project End Date

January 2020

Organization

Emory University

Year Awarded

2015

State

Georgia

Year Completed

2019

Project Type

Research Project

Health Conditions

Birth and Developmental Disorders

Genetic Disorders

Nutritional and Metabolic Disorders

Rare Diseases

Populations

Children -- 18 and under
Individuals with Rare Disease

Funding Announcement

Assessment of Prevention, Diagnosis, and Treatment Options

Project Budget

$2,529,864

Study Registration Information

HSRP20153560

NCT02519504

Page Last Updated:

April 9, 2020