I. Introduction
Carbohydrate metabolism disorders are inherited defects of enzymes involved in the processing of monosaccharides, disaccharides, or glycogen.
- They often present in infancy/early childhood with failure to thrive, hypoglycemia, hepatomegaly, and neurological symptoms.
- Two important groups:
- 1. Galactosemia – disorder of galactose utilization.
- 2. Glycogen storage disorders (GSDs) – defects in glycogen synthesis or breakdown.
II. Galactosemia
Molecular Basis
- Caused by deficiency of enzymes in galactose metabolism pathway:
- Classic galactosemia: deficiency of galactose-1-phosphate uridyltransferase (GALT) (most severe).
- Others: galactokinase deficiency (mild, cataracts only); UDP-galactose epimerase deficiency (rare).
Pathogenesis
- 1. Ingestion of galactose (milk/lactose) → cannot be metabolized properly.
- 2. Accumulation of galactose-1-phosphate (toxic to liver, kidney, brain).
- 3. Galactose reduced to galactitol by aldose reductase → cataract formation.
Clinical Features
- Onset: neonatal period after exposure to breast milk or formula.
- Symptoms:
- Vomiting, diarrhea, poor feeding, failure to thrive.
- Hepatomegaly, jaundice, risk of cirrhosis.
- Renal tubular dysfunction → aminoaciduria, acidosis.
- Cataracts (due to galactitol).
- Developmental delay/intellectual disability if untreated.
- Risk of sepsis (esp. E. coli).
Diagnosis
- Newborn screening: ↑ galactose or galactose-1-phosphate in blood.
- Enzyme assay (GALT activity).
- Genetic testing confirms mutation.
Management
- Eliminate galactose and lactose from diet (no milk).
- Early treatment prevents liver and kidney damage but long-term complications may persist (ovarian failure, learning difficulties)