What is the treatment plan for a pediatric patient diagnosed with galactosemia?

Treatment of Galactosemia

Immediate and lifelong dietary restriction of galactose is the only treatment for galactosemia and must be initiated as soon as the diagnosis is suspected to prevent acute mortality from liver failure, sepsis, and death. 1

Immediate Dietary Management

Classic Galactosemia (GALT Deficiency)

• Complete elimination of all galactose sources must begin immediately upon diagnosis or even suspicion of galactosemia, before confirmatory testing is complete 1, 2
• Switch to a galactose-free, lactose-free formula (soy-based or specialized formula free of sucrose, fructose, and lactose) 1, 3
• All breast milk and standard infant formulas must be discontinued immediately as they contain lactose, which breaks down into galactose 3, 2

Acute Neonatal Management

• Provide supportive care for life-threatening complications including liver dysfunction, coagulopathy, and sepsis (particularly E. coli sepsis in the first week of life) 1
• Monitor for failure to thrive, poor feeding, vomiting, hepatic dysfunction with jaundice, and coagulopathy 1, 4
• Be aware that blood transfusions can cause false-negative enzyme results by introducing donor RBCs with normal enzyme activity, requiring alternative diagnostic approaches 1

Long-Term Dietary Management

Infancy and Early Childhood

• Continue galactose-free, lactose-free formula throughout infancy 1, 3
• Introduce solid foods at the normal timeline (4-6 months), but restrict all galactose-containing foods including dairy products, organ meats, and certain legumes 4
• After the neonatal period, most countries advise a lactose-free diet without strict restriction of galactose-containing fruits and vegetables, though this remains somewhat controversial 4
• The goal is to reduce galactose intake to less than 10 mg per day 1

Nutritional Supplementation

• Prescribe a complete multivitamin with minerals as the restricted diet eliminates entire food groups and renders the diet nutritionally inadequate 1
• Provide calcium with vitamin D supplements if fortified galactose-free milk alternatives are not consumed 1
• Monitor for nutritional deficiencies, particularly vitamin D insufficiency, which occurs in 61.5% of patients despite supplementation 1

Monitoring and Follow-Up

Biochemical Monitoring

• Measure RBC galactose-1-phosphate (Gal-1-P) levels every 3-6 months to assess dietary compliance and therapeutic response, with a target range of 2-4 mg/dL 1
• Monitor blood and urine galactose levels to ensure adequate dietary restriction 5, 4

Developmental and Organ-Specific Monitoring

• Perform regular ophthalmologic examinations, particularly important for galactokinase (GALK) deficiency which primarily causes infantile cataracts 1
• Monitor for long-term complications including cognitive deficits, verbal dyspraxia, motor abnormalities, and primary ovarian insufficiency in females, which occur despite dietary treatment 6, 2, 4
• Assess speech, motor, and cognitive development regularly with early intervention for any delays 4

Important Caveats and Pitfalls

Duarte Galactosemia Exception

• Duarte galactosemia (DG) does NOT require dietary galactose restriction, as it does not cause life-threatening acute complications and dietary treatment is not related to developmental outcomes 7
• Duarte variant is characterized by approximately 25% residual GALT enzyme activity and occurs in compound heterozygosity with a Duarte 2 allele 7
• Testing for the 4-bp GALT promoter deletion distinguishes between D1 and D2 variants when Duarte variant is suspected 7

Limitations of Current Treatment

• Dietary restriction prevents acute neonatal death but does NOT prevent long-term complications affecting the brain and female gonads in classic galactosemia 6, 2, 4
• Most patients still develop cognitive deficits, speech problems, motor abnormalities, and primary ovarian insufficiency despite strict dietary adherence 6, 2
• Long-term complications may result from endogenous galactose synthesis or abnormal galactosylation that cannot be controlled by diet alone 4

Emerging Therapies

• Novel treatments under investigation include GALK1 inhibitors, pharmacological chaperones, enzyme replacement, nucleic acid therapies, and aldose reductase inhibitors, but none are currently available for clinical use 6
• Bone marrow transplantation has been studied in animal models but failed to protect liver and brain tissues despite normalizing RBC GALT activity 8