INTRODUCTION: Pompe disease, also know as type II glycogen storage disease, acid maltase deficiency is an autosomal recessive genetic disorder. It is a rare, progressive, debilitating and often fatal neuromuscular disorder. Respiratory failure is the major cause of morbidity and mortality among patients affected with Pompe disease (2). We present a case of an adult patient with Pompe disease and discuss the clinical, pathological presentation and investigations along with current approach to management of Pompe disease.
CASE PRESENTATION: A 48 year old Caucasian woman presented with five year history of progressive dyspnea, orthopnea, and hypersomnolence. She mobilized in wheelchair following a 14 year history of proximal muscle weakness, previously attributed to fibromyalgia.On examination, SpO2 88% on room air and she was unable to lie supine because of profound dyspnea. Neurological exam revealed modified Gower's maneuver and grade 3+ power in the proximal muscles.Pulmonary function test revealed moderate restrictive defect in keeping with chest wall or neuromuscular extrathoracic disease, and her arterial blood gases showed chronic respiratory acidosis with normal A-a gradient suggesting hypoventilation.Polysomnography showed sleep disordered breathing with severe obstructive sleep apnea and chronic respiratory failure related to hypoventilation syndrome. MRI brain was unremarkable. Sitting and supine spirometry revealed 47% drop in vital capacity suggesting diaphragmatic weakness, which was confirmed by the ultrasound of her diaphragms.She clinically benefited from institution of nocturnal noninvasive bilevel positive airway pressure ventilation.Muscle biopsy of vastus lateralis revealed lysosomal glycogen storage disease associated with marked accumulations of glycogen within muscle fibres, and vacuolar degeneration. These features were consistent with acid maltase deficiency, Pompe disease.She was subsequently started on enzyme replacement therapy with alfa glucosidase (Myozyme(r)) and physiotherapy to assist in airway clearance.
DISCUSSIONS: Pompe disease is caused by genetic mutation resulting in deficiency of alpha glucosidase enzyme (GAA), which converts lysosomal glycogen to glucose. This enzyme deficiency results in accumulation of glycogen resulting in cell dysfunction and eventually cell death primarily in skeletal, cardiac muscles, hepatocytes and the nervous system. Three forms of acid maltase deficiency have been described: infantile, juvenile and adult. Fewer than 10,000 patients worldwide are affected by this disease (1).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 proximal skeletal muscle weakness (2). About 15% of the patients who presented after the age of 18 years had died with a mean age of death of 44.9 years of age (1). It is diagnosed by measuring GAA enzyme activity.Treatment, until recently has been supportive measures, and the overall prognosis has been poor with the main cause of death being from respiratory failure. In 2006, the U.S. Food and Drug Administration (FDA), and the Health Canada approved enzyme replacement therapy with recombinant human alfa glucosidase (Myozyme(r)) as treatment for Pompe disease. This treatment has shown to extend survival and improve quality of life with improvements in respiratory and motor function.
CONCLUSION: Initial symptoms of Pompe disease are often nonspecific and slowly progressive leading to delay in diagnosis and death. 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.
DISCLOSURE: Anushya Chelvanathan, No Financial Disclosure Information; No Product/Research Disclosure Information