Write a short note on galactosaemia.

Definition

Types

Biochemical Basis of the Damage

GALT deficient → Galactose-1-phosphate accumulates → Traps inorganic phosphate → ATP depletion → Inhibits phosphoglucomutase → glycogenolysis blocked → hypoglycaemia → Direct toxicity to liver, kidney tubule and brain

Excess galactose → aldose reductase (NADPH used) → galactitol — cannot leave the lens → Osmotic water entry → fibre swelling and opacity → cataract

• Galactitol explains the cataract; galactose-1-phosphate explains everything else. That single distinction accounts for why galactokinase deficiency causes cataract alone

Clinical Features

• Appear within days of starting milk feeds
• Vomiting, diarrhoea, refusal of feeds, failure to thrive
• Jaundice and hepatomegaly, progressing to liver failure and cirrhosis
• Cataract — may be present within weeks
• Mental retardation if untreated
• Renal tubular acidosis with aminoaciduria
• Overwhelming escherichia coli sepsis — characteristic, and a frequent cause of death; galactose-1-phosphate impairs neutrophil function

Diagnosis

• Urine gives a positive Benedict test with a negative glucose oxidase strip — the classical screening finding
• Confirmed by assay of GALT in red blood cells
• Newborn screening by tandem mass spectrometry where available
• Do not rely on a galactose tolerance test — it is dangerous and contraindicated

Treatment and Applied Aspects

• Lifelong exclusion of galactose and lactose — stop breast and cow milk; use soya-based formula
• Early treatment reverses the acute illness and the cataract and prevents liver damage
• Long-term outcome is imperfect despite good control — learning difficulties, speech delay and premature ovarian failure in girls occur even in well-treated patients, probably from endogenous galactose production
• Galactose is not an essential nutrient — the epimerase reaction makes UDP-galactose from glucose, so a galactose-free diet is nutritionally safe
• Suspect it in any neonate with jaundice, hepatomegaly and sepsis, and stop milk immediately while awaiting results