Pompe Disease Flashcards
A 4-month-old infant is brought to the clinic due to poor feeding, respiratory difficulties, and failure to thrive. On examination, the infant has macroglossia, hypotonia, and significant hepatomegaly. Cardiac auscultation reveals a loud systolic murmur. Echocardiography shows hypertrophic cardiomyopathy. Laboratory studies demonstrate elevated creatine kinase (CK). Genetic testing confirms a mutation in the GAA gene. Which of the following best explains the pathophysiology of this condition?
A) Defective glycogenolysis due to liver phosphorylase deficiency
B) Impaired glycogen breakdown in lysosomes due to α-1,4-glucosidase deficiency
C) Defective gluconeogenesis due to glucose-6-phosphatase deficiency
D) Impaired fatty acid metabolism due to carnitine deficiency
E) Accumulation of amyloid fibrils in cardiac muscle
Answer: Impaired glycogen breakdown in lysosomes due to α-1,4-glucosidase deficiency
Explanation: Pompe disease is caused by a mutation in the GAA gene, leading to a deficiency of lysosomal acid maltase (α-1,4-glucosidase). This enzyme is essential for breaking down glycogen within lysosomes. The resulting glycogen accumulation leads to cellular damage, manifesting as hypertrophic cardiomyopathy, proximal muscle weakness, respiratory insufficiency, and failure to thrive. Macroglossia and hepatomegaly are also characteristic findings. Enzyme replacement therapy is the mainstay of treatment.
Incorrect Answers:
A) Liver phosphorylase deficiency is associated with Hers disease (Type VI glycogen storage disease), which does not cause cardiomyopathy or macroglossia.
C) Glucose-6-phosphatase deficiency is seen in Von Gierke disease (Type I glycogen storage disease), leading to fasting hypoglycemia and hepatomegaly, not hypertrophic cardiomyopathy.
D) Carnitine deficiency impairs fatty acid metabolism and leads to hypoketotic hypoglycemia, not glycogen storage.
E) Amyloid fibril deposition occurs in amyloidosis, not Pompe disease.
What is the gene defect and deficient enzyme in Pompe disease (Type II glycogen storage disease)?
Mutation in the GAA gene on chromosome 17q; deficient enzyme is lysosomal acid maltase (α-1,4-glucosidase)
What is the role of lysosomal acid maltase (α-1,4-glucosidase) in Pompe disease?
Hydrolyzes α-1,4 and α-1,6 linkages in glycogen within the acidic environment of the lysosome
What are the characteristic cardiac features of Pompe disease?
Hypertrophic cardiomyopathy, conduction blocks, and cardiomegaly
What are the characteristic muscular features of Pompe disease?
Proximal myopathy, hypotonia, and respiratory insufficiency
What are the systemic manifestations of Pompe disease?
Failure to thrive, macroglossia, and intracranial aneurysms.
Glucose levels are normal.
What complications are associated with untreated Pompe disease?
Progressive respiratory failure and early death
What is the primary mode of inheritance for Pompe disease?
Autosomal recessive inheritance
What is the main treatment approach for Pompe disease?
Enzyme replacement therapy with recombinant α-glucosidase
