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Difficulty: HardPediatric Genetic and Metabolic Disorders

Match each clinical vignette with the most likely deficient enzyme.

  • A 4-year-old boy is evaluated for severe bone pain in his lower extremities, easy bruising, and marked hepatosplenomegaly. A complete blood count reveals pancytopenia. Funduscopic examination shows no retinal abnormalities.Beta-glucocerebrosidase
  • A 4-day-old male neonate develops profound lethargy, tachypnea, and vomiting. Laboratory evaluation reveals a plasma ammonia level of 850 µmol/L (normal: 10-40), respiratory alkalosis, and markedly elevated urinary orotic acid.Ornithine transcarbamylase
  • A 2-year-old girl is evaluated for delayed ambulation and progressive lower extremity stiffness. Neurologic examination reveals spastic diplegia. Laboratory studies demonstrate markedly elevated plasma arginine with a mildly elevated plasma ammonia level.Arginase
  • A 6-month-old infant exhibits recurrent episodes of diaphoresis, vomiting, and profound lethargy following the introduction of fruit purees. Laboratory evaluation during an episode reveals severe hypoglycemia.Aldolase B

Answer

The correct matches are: the 4-year-old with bone pain matches Beta-glucocerebrosidase; the neonate with hyperammonemia and high orotic acid matches Ornithine transcarbamylase; the 2-year-old with spastic diplegia matches Arginase; and the infant with post-weaning hypoglycemia matches Aldolase B.
Each vignette represents a classic presentation of a distinct inborn error of metabolism. Gaucher disease (Beta-glucocerebrosidase deficiency) uniquely presents with bone pain, pancytopenia, and hepatosplenomegaly. Ornithine transcarbamylase deficiency causes severe neonatal hyperammonemia with elevated orotic acid. Arginase deficiency causes progressive spastic diplegia with elevated arginine. Hereditary fructose intolerance (Aldolase B deficiency) causes symptomatic hypoglycemia following fructose ingestion.

Step-by-Step Solution

1
Analyze the first vignette for signs of a specific lysosomal storage disease.
Hepatomegaly, pancytopenia, and bone pain without CNS involvement point to Gaucher disease type 1, caused by Beta-glucocerebrosidase deficiency.
Identifying the clinical triad of Gaucher disease is necessary for determining the correct enzyme.
2
Evaluate the second vignette for signs of a specific metabolic crisis.
Neonatal hyperammonemia, respiratory alkalosis, and elevated urinary orotic acid in a male strongly suggest X-linked Ornithine transcarbamylase deficiency.
Distinguishing urea cycle disorders requires analyzing ammonia and orotic acid levels.
3
Examine the third vignette for characteristic features of its urea cycle defect.
Progressive spastic diplegia and high arginine with mild hyperammonemia are the classic presentation of Arginase deficiency.
Arginase deficiency uniquely presents with spasticity rather than acute severe neonatal hyperammonemia.
4
Interpret the fourth vignette based on the dietary trigger and metabolic consequences.
Hypoglycemia and vomiting after introducing fruit (fructose) are pathognomonic for Hereditary fructose intolerance, caused by Aldolase B deficiency.
Correlating the onset of symptoms with dietary changes (fructose ingestion) identifies the specific carbohydrate metabolism defect.

Key Concept

Clinical presentations of pediatric genetic and metabolic disorders are uniquely linked to specific enzymatic defects, distinguishable by characteristic physical findings, laboratory abnormalities, and dietary triggers.
Estimated Time:2m 0s
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Topics

Pediatric Genetic and Metabolic Disorders

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