Galactosemia
A 5-week-old boy born to consanguineous parents has jaundice since the second week of life that has deepened as breastfeeding was established. He vomits after most feeds and has gained 200 g since birth. Temperature is 38.4 °C. Examination shows hepatomegaly and bilateral lens opacities. Direct bilirubin is 118 µmol/L, and urine is positive for reducing substances with a negative glucose oxidase dipstick. Which is the most likely diagnosis?
- A.Classic galactosemiaCorrect
- B.Hereditary fructose intolerance
- C.Biliary atresia
- D.Tyrosinemia type 1
Explanation
The combination of conjugated hyperbilirubinemia, hepatomegaly, vomiting that worsens with milk feeds, bilateral cataracts, and gram negative sepsis in a consanguineous family is the classic constellation of galactosemia. Deficiency of galactose-1-phosphate uridyltransferase causes accumulation of galactose-1-phosphate in liver, kidney, and brain, while excess galactose is reduced to galactitol in the lens, drawing in water and producing the characteristic oil droplet cataracts. Symptoms begin only after galactose exposure, which means after lactose containing breast milk or standard formula is started, explaining the symptom free first days of life. Affected infants have a strikingly increased susceptibility to Escherichia coli sepsis because galactose-1-phosphate impairs neutrophil function, and neonatal gram negative sepsis with jaundice should always prompt consideration of this diagnosis. Hereditary fructose intolerance produces a similar hepatic picture but only after fructose or sucrose exposure, typically when fruit, juice, or sucrose sweetened weaning foods are introduced at around 4 to 6 months, and it does not cause cataracts. Biliary atresia causes conjugated hyperbilirubinemia with pale acholic stools and dark urine in an otherwise well thriving infant and does not cause cataracts, sepsis predisposition, or reducing substances in the urine. Tyrosinemia type 1 causes liver failure with a cabbage-like odor, rickets from renal Fanconi syndrome, and a markedly raised alpha fetoprotein, again without cataracts. Immediate lifelong exclusion of galactose using a soy or elemental formula is life saving, and most countries include galactosemia in newborn screening.
Why each option
- A.
- Correct. Jaundice worsening with milk, hepatomegaly, cataracts, urinary reducing substances, and gram negative sepsis define classic galactosemia.
- B.
- Hereditary fructose intolerance appears only after fructose or sucrose exposure at weaning and does not cause cataracts.
- C.
- Biliary atresia gives cholestasis with acholic stools in a thriving infant, without cataracts or reducing substances in the urine.
- D.
- Tyrosinemia type 1 causes liver failure with renal Fanconi syndrome and a very high alpha fetoprotein but no cataracts.
Reference: Nelson Textbook of Pediatrics, 22nd ed., 2024
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