Studies of the natural history show that clinical manifestations are progressive, with poor prognosis and early exitus due to cardiorespiratory complications. Data from the International Pompe disease Registry (1) show that the most frequent muscle symptoms are hypotonia, inability to deambulation, weakness of proximal limbs muscles. Pneumonia and respiratory distress are commonly reported in
various age groups, while heart failure is prevalent in younger patients. In fact, severe heart involvement is typical of the classic infantile form and it can be detected by simple and cheap diagnostic Inhibitors,research,lifescience,medical investigations as chest x-ray and ECG that guide the diagnostic suspicion. Chest x-ray shows severe cardiomegaly and ECG Inhibitors,research,lifescience,medical reveals suggestive abnormalities like short PR, large QRS voltage, repolarization abnormalities and signs of left ventricular hypertrophy. Echocardiogram shows hypertrophic cardiomyopathy. Cardiac manifestations are absent or very mild in non classic infantile and
juvenile forms. Juvenile patients may present with progressive muscle weakness, myalgias, scapular winging and spine stiffness in combination with recurrent respiratory infections, respiratory failure, nocturnal apneas and selleckchem complications such as scoliosis or feeding problems. Difficulties in differential diagnosis may determine a variable diagnostic delay. A simple diagnostic algoritm in infantile forms has been proposed Inhibitors,research,lifescience,medical by national and international guidelines (2, 3). GAA enzymatic assay should be firstly performed in patients showing hypertrophic cardiomyopathy in combination with generalized hypotonia, hypertransaminasemia and incresased CPK. Muscle biopsy may show glycogen storage, but its usefulness in the diagnostic approach is Inhibitors,research,lifescience,medical controversial in infantile patients. Inhibitors,research,lifescience,medical GAA enzymatic assay should be performed in lymphocytes, fibroblasts or muscle biopsy. Recently innovative methods, such as measurement of GAA activity in dried blood spots by tandem mass spectroscopy, can be used to investigate suspected patients and in newborns screening programs. Moreover
a tetra glucose oligomer designated as Glc4 has been shown to be elevated in both urine and plasma of PD patients and it could be used as mafosfamide a non-invasive marker for diagnosis and monitoring of therapeutic response. Diagnosis of PD is confirmed by molecular analysis of GAA gene and identification of causative mutations is also helpful for familial screening and prenatal diagnosis. Although Pompe disease is a hereditary myopathy it is characterized by multisystem involvement; management of patients is multidisciplinary, involving different specialists. In classic infantile PD patients cardiac involvement is serious and cardiac supportive treatment is often needed. Respiratory involvement is due to concomitant factors as muscle weakness, reduced thoracic compliance, poor cough and recurrent infections.