The most common type of galactosemia (classic or type I) is diagnosed in the range of 1 in 30,000 to 1 in 48,000 births through newborn screening programs around the world. The other types of galactosemia are less common with type II likely occurring in fewer than 1 in 100,000 newborns and type III being very rare. The disease has been reported in all ethnic groups, but clinical variant galactosemia occurs most often in individuals of African descent and native Africans in South Africa with the specific GALT gene mutation. There seems to be an increased frequency of galactosemia in individuals of Irish ancestry.

Galactosemia is an autosomal recessive genetic disorder, whereby a child must inherit one defective gene from each parent to develop the disease. It is a carbohydrate metabolic disorder caused by disruptions or mutations in the GALT, GALK1, and GALE genes. These genes provide instructions for making enzymes that are responsible for breaking down galactose into glucose, and other molecules the body can store for energy use. The following are types of Galactosemia and can cause different patterns of signs and symptoms:

• Type I (Classic Galactosemia) - This is the most common and severe type caused by a deficiency in Galactose-1 phosphate uridyl transferase (GALT). 
• Type II (Galactokinase deficiency) - This is due to a deficiency of galactose kinase (GALK/GALK1).
• Type III (Galactose Epimerase deficiency) - This is due to a deficiency of galactose-6-phosphate epimerase (GALE).

Common symptoms and signs of classic galactosemia in infants can include feeding difficulties, lack of energy, failure to gain weight and grow, jaundice, liver damage, abnormal bleeding. abdominal pain, progressive sensorineural deafness, and amyloidosis (a rare disease in which abnormal proteins called amyloids build up and form deposits in organs, resulting in organ malfunction and eventually failure). In severe cases, bacterial infections (sepsis) and shock can occur.Type II Galactosemia causes fewer medical complications than classic galactosemia with affected infants developing cataracts but otherwise developing fewer long-term medical problems. Type III galactosemia can vary from mild to severe and can include cataracts, delayed growth and development, liver disease and kidney problems.

Classic galactosemia can be diagnosed when elevated levels of galactose-1-phosphate are found in red blood cells, and there is reduced GALT enzyme activity. In most infant cases, galactosemia can be diagnosed in newborn screening programs by using a small blood sample from the heel stick test (a test performed on newborns, in which a baby’s heel is pricked to collect a small sample of blood for testing).

Molecular genetic testing may be used to identify mutations in the GALT gene. 

A GALT isoelectric-focusing electrophoresis test for specific molecular diagnosis (this is a technique commonly used in laboratories to separate charged molecules, such as DNA according to size) and can be used to predict the GALT phenotype of an individual. The most common GALT mutation in white Europeans and North Americans replaces the amino acid glutamine with the amino acid arginine at position 188 in the enzyme (written as Gln188Arg or Q188R). Another mutation occurs almost exclusively in people of African descent, in which the amino acid leucine is replaced by the amino acid serine at position 135 (written as Ser135Leu or S135L).

There is no cure for galactosemia. Standard treatment for individuals with galactosemia involves following a lactose-restricted diet with lactose-free milk substitutes.

Children with galactosemia are at increased risk of delayed development, cataracts, speech difficulties, and intellectual disability. Depending on the severity of the condition, some children may require educational assistance, speech therapy, and hormone replacement therapy in cases of delayed puberty. Genetic counselling may be recommended in some families with children who have galactosemia.

National Organization for Rare Disorders. Galactosemia. 2019. Available from: https://rarediseases.org/rare-diseases/galactosemia/

Saleem, U., et al. Prevalence, Epidemiology and Clinical Study of Galactosemia. Journal of Applied Pharmacy. 2012. Available from: https://www.longdom.org/open-access/prevalence-epidemiology-and-clinical-study-of-galactosemia-.pdf

U.S. National Library of Medicine. Galactosemia. 2020. Available from: https://ghr.nlm.nih.gov/condition/galactosemia

U.S. National Library of Medicine. GALT Gene. 2020. Available from: https://ghr.nlm.nih.gov/gene/GALT#conditions