The term "galactosemia" means galactose in blood and results from an impaired ability to metabolize galactose.
Galactose is mainly present in milk and dairy products, where it is present in the form of lactose (literally sugar from the milk). After its ingestion, lactose is broken down into the two sugars galactose and glucose. Galactose is very important for the newborn, in which it represents 20% of source of energy, and for the biosynthesis of glycoconjugates.
In order to be used by the body, galactose must first be converted into glucose-1-phosphate and UDP-galactose by the Leloir pathway (figure).
Deficient activity of any of the Leloir pathway enzymes leads to galactosemia.
The most common is classic galactosemia (or type I galactosemia), which results from impaired activity of GALT, and occurs with a frequency of 1:16,000-60,000. Patients start developing symptoms a few days after birth which resolve by substituting the galactose-containing milk by soy milk or formula.
Unfortunately, early detection and early implementation of dietary treatment fail to prevent long-term complications, such as cognitive and ovarian impairments.
Type II galactosemia results from deficiency of GALK. The main clinical feature is cataracts in the neonatal period, which can be resolved or prevented by a galactose-restricted diet. There is lack of conclusive evidence indicative of long-term complications.
Type III galactosemia results from impaired activity of GALE and is described as ranging from a more benign peripheral form to the potentially lethal generalized form. The neonatal presentation of generalized form is amenable by diet, but, over the medium-long term, proves ineffective as long-term complications develop.
In 2018, several patients with a defect in GALM were first described, suggesting Type IV galactosemia.