General description

Galactosemia is an inborn error of carbohydrate metabolism characterized by the inability to metabolize galactose, a sugar primarily found in milk and dairy products. The disorder occurs due to disruptions or mutations in genes responsible for encoding enzymes in the Leloir pathway of galactose metabolism. Four main subtypes exist based on the specific enzyme deficiency:

Type 1 or classic galactosemia, the most severe and common form, results from mutations in the GALT gene leading to deficiency of galactose-1-phosphate uridylyltransferase (GALT). More than 250 mutations have been identified in the GALT gene. Type 2 results from galactokinase (GALK) deficiency, Type 3 from epimerase (GALE) deficiency, and a fourth variant called Duarte galactosemia represents a milder form.

Infants with this condition often appear healthy at birth but begin to show symptoms shortly after being exposed to galactose through milk. In the early phase, they may experience vomiting, poor appetite, jaundice, an enlarged liver, growth failure, and fluid buildup in the abdomen. Other signs include diarrhea, irritability, tiredness, and serious bacterial infections like E. coli sepsis. If not diagnosed and treated quickly, the illness can lead to severe complications such as liver failure, kidney issues, brain dysfunction, shock, and even death.

As the condition progresses, some infants may develop delayed psychomotor skills, cataracts, an enlarged liver and spleen, and seizures. Even with early treatment involving a galactose-free diet, many individuals face long-term issues. These can include problems with thinking, movement, speech and language, memory, learning, and behavior. Other lasting effects may involve tremors, difficulty with fine motor skills, low bone strength, cataracts, and reproductive challenges, particularly in females due to early ovarian problems.

References

1. Rossi-Espagnet, M. C., et al. "Neuroradiologic phenotyping of galactosemia: from the neonatal form to the chronic stage." American Journal of Neuroradiology 42.3 (2021): 590-596.