Clinical Scenario:
A 12-day-old male neonate is brought with poor feeding, recurrent vomiting, jaundice, and failure to gain weight. He was born at term and was well at birth. The symptoms started a few days after initiation of breastfeeding. On examination, he is lethargic, icteric, and has hepatomegaly. Ophthalmologic examination reveals bilateral lens opacities. Laboratory investigations show:
- Total bilirubin: 14 mg/dL (predominantly direct)
- AST/ALT: Elevated
- Blood glucose: 48 mg/dL
- Urine: Positive for reducing substances, negative for glucose
What is the most likely diagnosis?
A. Fructose intolerance
B. Galactosemia
C. Glycogen storage disease type I
D. Hereditary tyrosinemia type I
E. Neonatal hepatitis
Correct answer & Explanation:
Correct Answer B. Galactosemia
Discussion
This neonate has the classic features of classic galactosemia (galactose-1-phosphate uridyltransferase deficiency):
- Symptoms begin after exposure to milk (breast milk or formula)
- Poor feeding and vomiting
- Jaundice with liver dysfunction
- Hepatomegaly
- Hypoglycemia
- Cataracts
- Positive urine reducing substances despite negative urine glucose
Accumulation of galactose and galactitol in tissues leads to liver injury, cataracts, and systemic toxicity.
Why the Other Options Are Incorrect
A. Fructose intolerance
- Symptoms begin after introduction of fructose-containing foods (usually after 4–6 months of age), not in the neonatal period.
C. Glycogen storage disease type I
- Causes hepatomegaly and hypoglycemia but not cataracts or reducing substances in urine.
D. Hereditary tyrosinemia type I
- Causes liver dysfunction and renal tubular abnormalities but cataracts are not a typical feature.
E. Neonatal hepatitis
- May cause jaundice and hepatomegaly but does not explain cataracts and positive reducing substances in urine.
Postgraduate Pearl
A neonate with jaundice, hepatomegaly, cataracts, and reducing substances in urine after milk feeding should be assumed to have galactosemia until proven otherwise. The most common enzyme defect is galactose-1-phosphate uridyltransferase (GALT) deficiency.
Additional Viva Question
Which organism is classically associated with sepsis in galactosemia?
Answer: Escherichia coli
E. coli sepsis in a jaundiced neonate should raise strong suspicion for galactosemia.
