Galactosemia

Disease Overview

Galactosemia, which means “galactose in the blood,” refers to a group of inherited disorders that impair the body’s ability to process and produce energy from a sugar called galactose. When people with galactosemia injest foods or liquids containing galactose, undigested sugars build up in the blood. Galactose is present in many foods, including all dairy products (milk and anything made from milk), many baby formulas, and some fruits and vegetables.[3533][14968] The impaired ability to process galactose can be due to the deficiency of any of 3 enzymes, caused by mutations in different genes.[14975] There are 3 main types of galactosemia which are distinguished based on their genetic causes, signs and symptoms, and severity:[3533][14975][14976][14981][14977]

• Classic galactosemia (type 1) – the most common and severe type, caused by mutations in the GALT gene, and characterized by a complete deficiency of an enzyme called galactose-1-phosphate uridyl transferase (GALT). Early signs and symptoms include liver dysfunction, susceptibility to infections, failure to thrive, and cataracts. These can usually be prevented or improved by early diagnosis and treatment, but other progressive or long-term problems are common despite treatment. These include intellectual deficits, movement disorders, and premature ovarian failure (in females).
• Galactokinase deficiency (type 2) – caused by mutations in the GALK1 gene and characterized by a deficiency of the enzyme galactokinase 1. This type typically causes only the development of cataracts, which may be prevented or resolved with treatment. Rarely, this type causes pseudotumor cerebri (a condition which mimics the symptoms of a large brain tumor when no brain tumor is present).
• Galactose epimerase deficiency (type 3) – caused by mutations in the GALE gene and characterized by a deficiency of the enzyme UDP-galactose-4-epimerase. Symptoms and severity of this type depend on whether the deficiency is confined to certain types of blood cells or is present in all tissues. Some people with this type have no signs or symptoms, while others have symptoms similar to those with classic galactosemia. Like in classic galactosemia, many symptoms can be prevented or improved with treatment.

There is also a “variant” of classic galactosemia called Duarte variant galactosemia, in which a person has mutations in the GALT gene but has only partial deficiency of the enzyme. Infants with this form may have jaundice, which resolves when switched to a low-galactose formula. Some studies have found that people with this form are at increased risk for mild neurodevelopmental problems, but other studies have found there is no increased risk. The risk may depend on the extent of the deficiency.[14975][14982]

Inheritance of all types of galactosemia is autosomal recessive.[3533][14975] The diagnosis may be suspected based on symptoms or results of newborn screening tests, and can be confirmed by measuring enzyme activity and genetic testing.[14975] Depending on the type of galactosemia, treatment may involve removing galactose from the diet (as soon as the disorder is suspected), calcium supplementation, and individualized care for any additional symptoms.[14977] The long-term outlook for people with galactosemia varies depending on the type, symptoms present, and commitment to the diet.[14977]