Muscle Weakness and Respiratory Failure From an Orphan Disease: Adult Onset Pompe Disease (Acid Alpha-Glucosidase Deficiency)

Abstract

A 48 year old Caucasian women presents with approximately five year history of progressive dyspnea, orthopnea, hypersomnolence and proximal muscle weakness resulting in wheelchair use for mobilization. She was discovered to have sleep apnea, hypoventilation and chronic hypercapnic respiratory failure secondary to diaphragm and respiratory muscle weakness. She clinically benefited from institution of nocturnal noninvasive bilevel positive airway pressure (BIPAP) ventilation. Eventually, the diagnosis of Pompe disease was established by muscle biopsy. Pompe disease (glycogen storage disease type II, acid maltase deficiency) is a rare autosomal recessive genetic disorder that results in accumulation of glycogen in the lysosomal storage vacuoles. The imbalance promotes cell dysfunction and eventually cell death primarily in skeletal, cardiac muscle, hepatocytes and the nervous system. Three forms of acid maltase deficiency have been described: the infantile, juvenile and adult. In the adult form, in contrast to other neuromuscular diseases, severe respiratory failure may be the initial clinical feature and be preceded by only mild to moderate skeletal muscle weakness as in our case. Treatment, until recently have been supportive measures, and the overall prognosis was poor with the main cause of death being from respiratory failure. In 2006, Health Canada approved enzyme replacement therapy with alfa glucosidase (Myozyme(registered trademark)) as treatment for Pompe disease. This treatment has extended survival and improved quality of life with improvements in respiratory and motor function. Initial symptoms are often nonspecific and slowly progressive leading to delay in diagnosis. The importance of considering this Orphan Disease as a differential diagnosis in patients presenting with respiratory failure and muscle weakness has now become even more critical with the availability of effective treatment with enzyme replacement. We will present the clinical, pathological presentation and investigations along with current approach to management of Pompe disease.