Clinical scenario: Infant | Floppy | Cardiomyopathy | Macroglossia
A 4-month-old infant is brought with poor feeding, generalized hypotonia, and progressive respiratory distress. Examination reveals macroglossia, marked hypotonia, absent deep tendon reflexes, and hepatomegaly. Cardiac examination demonstrates cardiomegaly, and echocardiography shows concentric hypertrophic cardiomyopathy with preserved systolic function. Serum creatine kinase is elevated. Which of the following is the most appropriate next step in management?
A. Enzyme replacement therapy with alglucosidase alfa
B. High-dose oral corticosteroids
C. Liver transplantation
D. Oral cornstarch therapy
E. Propranolol therapy
Correct answer & Explanation:
Correct Answer:
A. Enzyme replacement therapy with alglucosidase alfa
Explanation
Pompe disease (Glycogen Storage Disease Type II) is an autosomal recessive lysosomal storage disorder caused by deficiency of acid α-glucosidase (acid maltase, GAA gene). Glycogen accumulates within lysosomes, primarily affecting cardiac, skeletal, and respiratory muscles.
The classic infantile form presents with:
- Severe hypotonia (“floppy infant”)
- Feeding difficulties and failure to thrive
- Progressive respiratory insufficiency
- Macroglossia
- Hypertrophic cardiomyopathy
- Elevated serum creatine kinase (CK)
The treatment of choice is enzyme replacement therapy (ERT) with alglucosidase alfa, which should be started as early as possible. Early initiation significantly improves survival, cardiac function, and motor outcomes.
Why the other options are incorrect
- B. High-dose oral corticosteroids – No established role in treating Pompe disease.
- C. Liver transplantation – Pompe disease is a systemic lysosomal disorder; liver transplantation is not indicated.
- D. Oral cornstarch therapy – Used in GSD I (Von Gierke disease) to prevent fasting hypoglycemia, not in Pompe disease.
- E. Propranolol therapy – Does not treat the underlying disease or improve outcomes in Pompe disease.
MRCPCH Pearl
Infant + floppy baby + hypertrophic cardiomyopathy + macroglossia + elevated CK = Pompe disease until proven otherwise.
The diagnosis is confirmed by demonstrating reduced acid α-glucosidase enzyme activity (in dried blood spot or leukocytes) and/or identifying biallelic pathogenic variants in the GAA gene.
References:
- Nelson Textbook of Pediatrics, 22nd Edition.
- MRCPCH Foundation of Practice Curriculum.
- International Consensus Guidelines for the Diagnosis and Management of Pompe Disease.
