The Molecular Biology of Galactosemia

by | Nov 20, 2018 | Health Featured

Galactose is a monosaccharide sugar that forms lactose when combined with glucose. Lactose can be found in milk and various food products made with dairy-derived ingredients. The hydrolysis of this molecule is catalyzed by the enzyme’s lactase and β-galactosidase. Galactosemia is a rare autosomal recessive, genetic metabolic disorder that causes the accumulation of galactose in blood. It occurs in 1 in 30,000 to 60,000 newborns and there is still no cure (1).

Understanding Galactosemia

When metabolized through the Leloir pathway in the liver, galactose is converted into glucose. Glucose is then catabolized by a reaction known as glycolysis, which provides cells with the necessary energy to carry out metabolic processes. The altered metabolism of galactose results in an elevated, toxic blood galactose concentration known as galactosemia. It is caused by deficient catalytic activity of galactokinase, galactose-1-phosphate uridyltransferase, and UDP-galactose 4-epimerase (2).

Galactosemia can cause long-term complications such as brain damage, kidney damage, learning disabilities, and reduced bone density, among others. The only way to manage this disorder is by avoiding the intake of lactose and galactose in the diet. There are three main types of galactosemia:

Type 1, the most common and severe type, is characterized by a deficiency of the galactose-1-phosphate uridyltransferase (GALT) due to a mutation in the GALT gene. Some of the main health complications are liver dysfunction and susceptibility to infections, which can be reduced with early diagnosis (3).

Type 2 is caused by a deficiency of the enzyme galactokinase 1 (GALK1), which takes place due to a mutation of the GALK1 gene. Cataracts are the most frequent health complications related to this disorder (2). 

Type 3 occurs due to a deficiency of the enzyme UDP-galactose 4-epimerase (GALE) caused by mutations in the GALE gene. The severity of this type of galactosemia depends on the patient and which tissues become affected (4).

Importance of Early Diagnosis for A Disorder Without A Cure

Newborns with classic galactosemia usually present early manifestations in the first few days after birth as a result of feedings that contains galactose, such as breast milk or formula. The type of galactosemia can be determined by the utilization of modern effective protein purification methods, and early detection is the key to controlling symptoms. If treated early, the vast majority of infants can have a normal life. Prenatal diagnosis can also be carried out by using fibroblasts cultured from amniotic fluid.

Even though there is still no effective therapy for galactosemia, the identification of the mutations responsible for the development of galactosemia brings hope related to future advances in developing a drug. The utilization of some compounds to successfully lower galactose-1-phosphate concentration in patient cells already anticipates a promissory future (5). There is still a lot to be done, but science is undoubtedly on the right path. 


  2. Coelho D. Sweet and sour: an update on classic galactosemia. J Inherit Metab Dis. 2017; 40(3): 325–342. Published online 2017 Mar 9. doi:  [10.1007/s10545-017-0029-3].
  3. Maratha A, et al. Classical galactosaemia: novel insights in IgG N-glycosylation and N-glycan biosynthesis. Eur J Hum Genet. 2016 Jul; 24(7): 976–984. Published online 2016 Jan 6. doi:  [10.1038/ejhg.2015.254
  4. Brokate-Llanos A, et al. Developmental Defects in a Caenorhabditis elegans Model for Type III Galactosemia. Genetics. 2014 Dec; 198(4): 1559–1569. Published online 2014 Oct 8. doi:  [10.1534/genetics.114.170084]
  5. Tang M, et al. Innovative Therapy for Classic Galactosemia – Tale of Two HTS. Mol Genet Metab. Author manuscript; available in PMC 2013 Jan 1. Published in final edited form as: Mol Genet Metab. 2012 Jan; 105(1): 44–55. Published online 2011 Oct 1. doi:  [10.1016/j.ymgme.2011.09.028]
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