Galactosemia

Table of Contents

• Galactose Metabolism Pathway
• Genetic Basis
• Classic Galactosemia
• Duarte Galactosemia
• Epimerase Deficiency
• Galactokinase Deficiency

Galactose Metabolism Pathway

Galactose is metabolized through a series of enzymatic steps:

Metabolic Flow

Genetic Basis

All defects in galactose metabolism are inherited in an autosomal recessive (AR) pattern.

Classic Galactosemia

Overview

• Cause: Deficiency of GALT (Galactose-1-phosphate uridyltransferase)
• Incidence: 1 in 10,000–70,000 live births
• Onset: Within days of milk introduction

Clinical Presentation

• Hypoglycemia
• Vomiting, diarrhea
• Poor weight gain
• Seizures
• Hepatomegaly, jaundice, liver failure
• Hemolytic anemia
• Renal tubular dysfunction
• Neonatal E. coli sepsis (critical diagnostic clue)
• Cataracts (due to galactitol accumulation)
• Premature ovarian failure (hypergonadotropic hypogonadism)
• Mental retardation (linked to dietary control)

Diagnosis

• Newborn screening
• Urinary reducing substances (positive, but no glucosuria)
• ↓ GALT activity in RBCs
• Note: Prior transfusions may interfere with testing

Treatment

• Eliminate dietary galactose
• Infants: Switch to soy or protein hydrolysate formula
• Children/Adults: Avoid milk and milk products
• Avoid beans (e.g., garbanzo, black beans—high galactose content)
• Supplement: Calcium and vitamin D
• Monitoring: Annual eye exams and neurodevelopmental assessments

Duarte Galactosemia

• Mild form with >50% residual enzyme activity
• Most are asymptomatic
• No dietary restrictions needed

UDP-Galactose Epimerase Deficiency

• Presentation: Similar to classic galactosemia
• Cause: Deficiency in UDP-galactose 4-epimerase

Galactokinase Deficiency

• Key Feature: Rapidly progressive cataracts in the first week of life
• Glucosuria
• No liver involvement
• Management: Lactose-free diet