MCQ NO 1:
A 7-day-old exclusively breastfed male neonate is brought with poor feeding, lethargy, and recurrent vomiting. He was well until the fifth day of life. Examination reveals hypotonia and depressed neonatal reflexes. Laboratory investigations show:
Blood glucose: 92 mg/dL
Serum ammonia: 850 µmol/L
Arterial blood gas: pH 7.42
Serum lactate: Normal
Urine ketones: Negative
What is the most likely diagnosis?
A. Fatty acid oxidation defect
B. Organic acidemia
C. Urea cycle defect
D. Galactosemia
E. Maple syrup urine disease
Correct Answer
✅ C. Urea cycle defect
Explanation
The hallmark findings are:
Neonatal encephalopathy
Severe hyperammonemia
Normal glucose
Normal lactate
Absence of significant metabolic acidosis
This combination is classic for a urea cycle defect.
MCQ NO 2:
A 9-month-old boy is brought with recurrent episodes of vomiting, lethargy, and seizures, particularly during periods of fasting or intercurrent illness. His parents report that he becomes symptomatic after prolonged overnight fasting but improves rapidly after receiving intravenous glucose. On examination, he is lethargic with mild hepatomegaly. Laboratory investigations during an episode reveal:
Blood glucose: 32 mg/dL
Serum ketones: Absent
Serum ammonia: Normal
Arterial blood gas: Normal
What is the most likely diagnosis?
A. Galactosemia
B. Glycogen storage disease type I
C. Medium-chain acyl-CoA dehydrogenase deficiency
D. Maple syrup urine disease
E. Urea cycle defect
Correct Answer
✅ C. Medium-chain acyl-CoA dehydrogenase deficiency
Discussion
This child has:
Recurrent episodes precipitated by fasting
Severe hypoglycemia
Absent ketones (hypoketotic hypoglycemia)
Improvement with glucose administration
Mild hepatomegaly
The inability to generate ketone bodies during fasting is the key clue. Normally, fatty acid oxidation provides energy and ketones during fasting. In MCAD deficiency, fatty acid oxidation is impaired, leading to:
Hypoglycemia
Low or absent ketones
Lethargy, seizures, coma
Risk of sudden death during fasting illnesses
Why the Other Options Are Incorrect
A. Galactosemia
Presents after milk feeding with jaundice, hepatomegaly, and cataracts.
Hypoketotic hypoglycemia is not typical.
B. Glycogen Storage Disease Type I
Causes fasting hypoglycemia but is usually associated with ketosis, hyperlactatemia, and marked hepatomegaly.
D. Maple Syrup Urine Disease
Presents with poor feeding, encephalopathy, and ketosis.
Characteristic sweet odor of urine.
E. Urea Cycle Defect
Presents with hyperammonemic encephalopathy.
Blood glucose is usually normal.
Postgraduate Pearl
Hypoketotic hypoglycemia in a child with recurrent fasting intolerance is a classic clue to a fatty acid oxidation disorder, particularly Medium-chain acyl-CoA dehydrogenase deficiency (MCAD deficiency). The inability to produce ketones despite profound hypoglycemia is the diagnostic hallmark.
MCQ NO 3:
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
✅ 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.