Pompe Disease (diagnosis and management)

Question 1

What is Pompe Disease? (also known as acid maltase deficiency [AMD] or glycogen storage disease type II [GSD11])

Answer 1

• Rare, progressive, and often fatal muscular disease
• Underlying pathology: deficiency of the enzyme acid alpha-glucosidase (GAA) which hydrolyzes lysosomal glycogen.
• Variable clinical presentation with respect to age of onset, rate of disease progression, and extent of muscular involvement (skeletal, respiratory, cardiac)

Question 2

Inheritance Pattern

Answer 2

Autosomal Recessive; caused by a deficiency of the lysosomal enzyme acid-alpha-glucosidease (GAA)

Question 3

History of Pompe disease

Answer 3

• First recognized lysosomal storage disease and is the only glycogen storage disease that is also a lysosomal storage disease

Question 4

Clinical presentation range in severity of Pompe disease

Answer 4

• Ranges from rapidly progressive infantile form (uniformly lethal) to a more slowly progressive late-onset form
• In general, disease severity typically correlates inversely with residual acid alpha-glucosidase (GAA) activity

Question 5

Patients with infantile Pompe disease present in the first few months of life with _______________________

Answer 5

• hypertrophic cardiomyopathy
• generalized muscle weakness
• hypotonia
• cardiomegaly
• respiratory distress
• failure to thrive
• followed by death from cardiorespiratory failure usually by 1 year

Question 6

Late-onset Pompe disease is characterized by ________________________________

Answer 6

• lack of severe (typically absence of) cardiac involvement and a less dismal short-term prognosis
• Can present at any age
• Symptoms are related to progressive skeletal muscle dysfunction
• proximal lower limb and paraspinal trunk muscles are usually affected first, followed by involvement of the diaphragm and accessory muscles of respiration

Question 7

Diagnostic testing of Pompe disease

Answer 7

• Infantile-onset: virtual absense of GAA activity in tissues such as cultured fibroblasts from skin biopsy, muscle biopsy, purified lymphocytes, mononuclear cells and lymphoid cell lines
• Late-onset: markedly reduced GAA activity in tissues

Question 8

Current gold standard of diagnostic testing of Pompe disease

Answer 8

• Measurement of GAA activity in skin fibroblasts (downside: can take up to 4 - 6 weeks)