Duarte Galactosemia

Excerpt

Clinical characteristics: Infants with Duarte galactosemia who receive breast milk or a high galactose-containing formula (dairy milk-based formula) are asymptomatic. Current data suggest that infants and children with Duarte galactosemia are not at increased risk for acute or long-term developmental complications regardless of dietary exposure to galactose in infancy. Premature ovarian insufficiency, which is common in classic galactosemia, has not been reported for girls or women with Duarte galactosemia.

Diagnosis/testing: The diagnosis of Duarte galactosemia is established in a proband with partial deficiency of erythrocyte galactose-1-phosphate uridylyltransferase (GALT) enzyme activity that is typically about 25% of control activity; and a heterozygous GALT pathogenic variant and either a heterozygous or homozygous Duarte GALT allele (D₂ allele) identified by molecular genetic testing.

Management: Treatment of manifestations: Most health care providers do not recommend dietary intervention for infants with Duarte galactosemia. A small number of providers recommend dietary galactose restriction in at least the first year of life for individuals who may have Duarte galactosemia, because locally available testing is insufficient to distinguish Duarte galactosemia from other forms of galactosemia. When dietary galactose is restricted in infancy, a galactose challenge should be considered by age 12 months with measurement of erythrocyte galactose-1-phosphate concentration. If the galactose-1-phosphate concentration is within the normal range (<1.0 mg/dL), dietary restriction of galactose is generally discontinued.

Surveillance: If dietary intervention is not recommended, surveillance is not typically performed. For infants placed on dietary galactose restriction, a galactose challenge is recommended at age one year. If the erythrocyte galactose-1-phosphate concentration is >1.0 mg/dL following a galactose challenge, galactose restriction may be resumed and a galactose challenge and measurement of erythrocyte galactose-1-phosphate concentration may be repeated every four to six months until the erythrocyte galactose-1-phosphate concentration is <1.0 mg/dL.

Agents/circumstances to avoid: Some health care providers recommend avoiding all high galactose foods (e.g., dairy milk products) for the first year of life, followed by a galactose challenge; other health care providers argue that this precaution is neither warranted nor desirable.

Genetic counseling: Duarte galactosemia is inherited in an autosomal recessive manner. Molecular genetic testing is needed to clarify the genetic status of the parents of the proband. Typically, one parent of a child with Duarte galactosemia is heterozygous for the D₂ allele and the other parent is heterozygous for a GALT pathogenic variant. If one parent is heterozygous for the D₂ allele and the other parent is heterozygous for a GALT pathogenic variant, each sib has at conception: a 25% chance of having Duarte galactosemia; a 25% chance of being an asymptomatic carrier of a D₂ allele; a 25% chance of being an asymptomatic carrier of a GALT pathogenic variant; and a 25% chance of being unaffected and having neither the GALT pathogenic variant nor the D₂ allele. Risks to sibs are different for other parental genotypes. Individuals with Duarte galactosemia are at increased risk for having a child with classic or clinical variant galactosemia. Once the GALT pathogenic variant and D₂ allele(s) have been identified in a family member with Duarte galactosemia, carrier testing for at-risk relatives and prenatal/preimplantation genetic testing are possible.