Symptoms of Pompe disease
How does acid maltase deficiency (Pompe disease; glycogenosis type II) present?
Acid maltase deficiency is one of the two most common GSD. It is caused by mutations of the gene that codes for the intralysosomal enzyme alpha-glucosidase (GAA) that catalyzes the release of glucose from maltose, oligosaccharide, and glycogen in lysosomes. Its deficiency is transmitted by autosomal recessive inheritance and produces three different clinical syndromes depending on the severity of the enzyme deficiency.
1. The infantile form causes symptoms of muscle weakness, hypotonia, and congestive heart failure that begins shortly after birth and progresses to death within the first 2 years of life.
2. The childhood and juvenile forms present in the first two decades with progressive proximal muscle weakness. Death is usually from respiratory failure and occurs before the age of 30 years.
3. The adult form presents in the third to sixth decades of life with insidious, painless limb-girdle weakness, and an elevated CK. The respiratory muscles are usually affected and 30% present with respiratory failure. This form is frequently misdiagnosed as polymyositis or limb girdle muscular dystrophy (LGMD). Muscle biopsy reveals diagnostic findings in only two-thirds of cases. Typical histologic changes involve muscle fibers with vacuoles filled with periodic acid-Schiff positive material and stain intensely for acid phosphatase, another lysosomal enzyme. The electromyogram (EMG) shows myopathic changes, electrical irritability, and pseudomyotonic discharges without clinical evidence of myotonia. The diagnosis is confirmed by genetic testing in conjunction with decreased GAA enzyme activity in the blood. Treatment involves enzyme replacement therapy with rhGAA.
Pearl : Consider this diagnosis in any patient suspected of muscle disease with significant respiratory insufficiency.
