About Galactosemia
The Basics
Galactosemia is a rare genetic metabolic disorder in which infants are unable to convert galactose, a milk sugar, into glucose, which is used for energy by the body. Galactosemia is inherited, meaning that if both parents carry a nonworking copy of a gene that can cause the disorder, their children have a 25% chance of being affected by it. About 1 in every 40,000 to 1 in every 60,000 newborns are affected. People with galactosemia cannot tolerate any form of milk or other foods containing galactose. Newborns who are diagnosed with galactosemia through a mandatory newborn screening program need to be put on a special lactose-free diet right after birth to prevent serious damage to the organs. If dietary restrictions are not implemented within 10 days or milk is ingested, the infant will die due to serious bacterial blood infections or cirrhosis. Other initial signs include vomiting, lethargy, refusal to feed, cataracts, and jaundice.
History of Galactosemia
The first description of a newborn with galactosemia was in 1908 by von Ruess, when a breastfed infant was found to have toxic levels of galactose in the urine (galactosuria). In 1935, an infant with galactosuria was found to respond well to a diet that removed milk products containing lactose at 10 months of age. In 1956, Kalckar determined that the GALT enzyme was missing in classic galactosemia, causing the buildup of undigested galactose. For the next three decades two other forms of galactosemia, Type II and III, were identified. The first attempt at newborn screening for classic galactosemia was in 1963. By 1988, the GALT gene that encodes for the enzyme was described.
Modern biochemical studies have depicted that enzyme deficiencies can be attributed to protein misfolding and instability. By the 2000s, newborn screening had become more widespread, and revised diet guidelines were implemented. In 2020, the first clinical trial for galactosemia began. After a century of progress, improved therapies incorporating novel drugs have shown promise. However, the biology behind galactosemia is complex and still not fully understood.
Types of Galactosemia
Complications
Even if children receive treatment early on and follow dietary guidelines, delays in development and cognition are common. Though the level of symptoms will vary from mild to severe, long-term issues may include feeding problems, learning disabilities, neurological impairments, cataracts, and ovarian failure.
Diagnosis
Galactosemia is often challenging to diagnose because physical symptoms may not be present immediately after birth. Newborn screening and genetic tests are thus crucial because the earlier galactosemia is identified, the less likely a child will have irreversible complications.