Galactosemia is a rare, inherited metabolic disorder preventing the body from properly processing the simple sugar galactose, a component of lactose. This inability to metabolize galactose leads to the accumulation of toxic substances in the blood and tissues. Early detection is important because delayed diagnosis can result in severe, life-threatening complications, particularly in newborns. While specialized testing is required for diagnosis, prompt recognition of a baby’s symptoms often dictates the speed of life-saving intervention.
The Metabolic Basis of Galactosemia
Galactosemia arises from a deficiency in one of the enzymes responsible for breaking down galactose into usable energy. The most common and severe form, Classic Galactosemia, involves a defect in the enzyme Galactose-1-phosphate uridyltransferase (GALT). GALT is part of the Leloir pathway, which converts galactose into glucose, the body’s main energy source.
A deficiency in GALT activity causes a buildup of Galactose-1-phosphate (Gal-1P) in the cells, which is toxic to organs like the liver, brain, and kidneys. Less common types of the disorder involve different enzymes, such as Galactokinase (GALK) deficiency or Galactose Epimerase (GALE) deficiency. A milder variant, Duarte Galactosemia, also involves the GALT enzyme but typically retains some enzyme activity, leading to less severe symptoms.
Recognizing Early and Acute Symptoms
Infants with Classic Galactosemia are typically born without symptoms, but acute signs emerge rapidly once milk feeding begins, usually within the first few days or weeks of life. Since lactose in breast milk and standard formula contains galactose, ingestion quickly triggers a toxic buildup. These babies often exhibit a failure to thrive, showing poor weight gain and growth despite adequate calorie intake.
Initial symptoms are often nonspecific, including vomiting, lethargy, poor feeding, and a weakened sucking reflex. As the condition progresses, severe jaundice (yellowing of the skin and eyes) and hepatomegaly (an enlarged liver) develop due to liver dysfunction. A dangerous complication is susceptibility to severe bacterial infection, most commonly E. coli sepsis, which can be fatal if not immediately addressed. These acute symptoms often necessitate emergency medical care and prompt treatment before formal newborn screening results are finalized.
Diagnostic Methods and Confirmation Testing
The primary method for initial detection is the mandatory newborn screening, typically performed via a heel stick blood test within the first few days after birth. Screening tests look for two main indicators: the level of total galactose (galactose plus Gal-1P) in the blood and the activity level of the GALT enzyme in red blood cells. A result showing low or absent GALT enzyme activity, or significantly elevated galactose levels, suggests a presumptive positive diagnosis.
If the screening is abnormal, follow-up quantitative testing is immediately ordered to confirm the diagnosis and determine severity. This involves a quantitative enzyme assay that precisely measures GALT enzyme activity in red blood cells. Classic Galactosemia is typically confirmed if GALT enzyme activity is absent or barely detectable, often less than 1% of the normal value.
Genetic testing, or DNA sequencing, is also used to classify the type of Galactosemia and identify specific mutations in the GALT gene. The most frequent mutation found in Classic Galactosemia is the Q188R variant. Genetic analysis confirms the diagnosis by identifying two pathogenic variants in the GALT gene, solidifying the inherited nature of the disorder.
Essential Management and Treatment
Following a presumptive or confirmed diagnosis, immediate and total removal of galactose from the diet is the only effective treatment for the acute phase of the disorder. This involves strictly eliminating all sources of lactose and galactose, including breast milk and standard milk-based formulas. Infants are typically switched immediately to a lactose-free formula, such as a soy-based or elemental formula.
This restriction must be maintained lifelong under the guidance of a metabolic specialist and a registered dietitian. Caregivers are taught to carefully read food labels to avoid ingredients like dry milk solids, casein, and whey. Since the diet eliminates dairy, a primary source of calcium and Vitamin D, supplementation is required to maintain bone health. Consistent monitoring by metabolic specialists is necessary to manage the condition and track long-term health outcomes.