Galactosemia (GALT)
Galactosemia is inherited in an autosomal recessive pattern. Normally a person has two functional copies of the GALT gene. In people with galactosemia, both copies of the gene have a mutation and there is a deficiency of the critical enzyme. Each parent of a newborn with galactosemia typically has one functional copy and one mutated copy of the GALT gene and is considered a carrier. When both parents are carriers, the chance of a newborn inheriting two mutated genes is 25%.
Carriers of galactosemia do not typically have symptoms.
The life-threatening complications of galactosemia present in the first 7 - 10 days after birth if the infant is untreated. Symptoms include jaundice, feeding difficulty, lethargy, failure to thrive, hepatomegaly and bleeding diasthesis. Other complications may include sepsis and shock. Long term symptoms included delayed developmental milestones, verbal dyspraxia, cataracts, intellectual disability, and, in females, premature ovarian insufficiency.
There are variants of galactosemia that may be detected on newborn screening. One example of this is the Duarte variant, N314D in the GALT gene. When present with a second GALT gene mutation, this produces about 25% the normal amount of GALT enzyme and results in mild or asymptomatic cases of galactosemia.
- Incidence: Galactosemia has an incidence of approximately 1 in 58,000 newborns.
- New York State Method of Screening (First Tier): Screening for galactosemia is accomplished by measuring galactose-1-phosphate uridyl transferase enzyme activity by the Beutler assay.
Second Tier Screening: Sequencing of the GALT gene - Testing can be affected by: Exposure of the specimen to heat and humidity can cause breakdown of the GALT enzyme, resulting in a false positive. Transfusion in a newborn may also affect the Beutler test result. There are two other forms of galactosemia: type II (also called galactokinase deficiency), caused by mutations in the GALK1 gene, and type III (also called galactose epimerase deficiency), caused by mutations in the GALE gene. Neither of these conditions are detected on the New York State Newborn Screen.
- Interpretation/reporting of data: Results are reported as screen negative or as a referral. Prompt consultation with a specialist is required for a referral.
- Referral to Specialty Care Center: Patients with an abnormal newborn screen for galactosemia are referred to an Inherited Metabolic Disorder Specialty Care Center for evaluation by a biochemical geneticist trained in the diagnosis and treatment of galactosemia.
Diagnostic testing may include measurement of galactose-1-phosphate uridyl transferase enzyme activity in erythrocytes and/or additional molecular genetic testing of the GALT gene.
Newborns who screen positive for galactosemia should immediately begin a lactose-restricted diet. Lifelong dietary restriction of lactose is recommended.
If the lactose-restricted diet is started promptly, the early symptoms of galactosemia resolve or are prevented entirely. Even with early and adequate therapy, the long-term effects in older children and adults can include cataracts, speech defects, poor growth, poor intellectual function, neurologic deficits and premature ovarian failure. These potential long-term complications are due to endogenous production of galactose.
Galactosemia is a disorder of carbohydrate metabolism caused by a defective or absent enzyme, galatose-1-phosphate uridyltransferase (GALT). This enzyme is responsible for metabolizing galactose to produce glucose. Lactose, which is ingested via milk and milk products, is broken down into galactose and glucose. Infants with a defective or absent GALT enzyme cannot metabolize the galactose produced as a by-product of milk digestion. As a result, galactose accumulates in the blood which can become a life-threatening situation. Mutations in the GALT gene cause dysfunction or absence of the GALT enzyme.