Children with Pompe disease: clinical characteristics, peculiar features and effects of enzyme replacement therapy

Pompe disease is a metabolic myopathy. Since the first description of the disease in 1932 by J.C. Pompe,1 tremendous progress has been made from discovering the biochemical and genetic basis of the disease to developing enzyme replacement therapy (ERT). With this therapy, the management of Pompe disease has moved from supportive care alone, to a disease-specific intervention aimed at correcting the underlying enzymatic defect. While in the past research mainly concentrated on elucidating the biochemical pathways and pathophysiology of Pompe disease, nowadays focus has shifted towards documenting the natural history of the disease and studying the effect of the new treatment. A structured follow-up of a large number of patients is difficult in a rare disorder like Pompe disease. The establishment of an expert center for Pompe disease at the Erasmus MC University Medical Center has helped us to systematically study all Pompe patients living in the Netherlands. At present, we follow 149 patients, of which 18 patients are diagnosed with classic-infantile Pompe disease; and 20 children and 111 adults with less progressive forms of the disease. The studies in this thesis have focused on children with Pompe disease. Our aim was to delineate the first presentation and clinical characteristics of the disease and to study the long-term effects of enzyme replacement therapy with recombinant human alpha-glucosidase

Cardiac outcome in classic infantile Pompe disease after 13\xe2\x80\xafyears of treatment with recombinant human acid alpha-glucosidase

Background: Cardiac failure is the main cause of death in untreated classic infantile Pompe disease, an inheritable metabolic myopathy characterized by progressive hypertrophic cardiomyopathy. Since the introduction of enzyme replacement therapy (ERT), survival has increased significantly due to reduced cardiac hypertrophy and improved cardiac function. However, little is known about ERT\'s long-term effects on the heart. Methods: Fourteen patients were included in this prospective study. Cardiac dimensions, function, conduction and rhythm disturbances were evaluated at baseline and at regular intervals thereafter. Results: Treatment duration ranged from 1.1 to 13.9 years (median 4.8 years). At baseline, all patients had increased left ventricular mass index (LVMI) (median LVMI 226 g/m2, range 98 to 599 g/m2, Z-score median 7, range 2.4\xe2\x80\x9312.4). During the first four weeks, LVMI continued to increase in six patients. Normalization of LVMI was observed in 13 patients (median 30 weeks; range 3 to 660 weeks). After clinical deterioration, LVMI increased again slightly in one patient. At baseline, PR interval was shortened in all patients; it normalized in only three. A delta-wave pattern on ECG was seen in six patients and resulted in documented periods of supraventricular tachycardias (SVTs) in three patients, two of whom required medication and/or ablation. One patient had severe bradycardia (35 beats/min). Conclusion: This study shows that ERT significantly reduced LVMI, and sustained this effect over a period of 13.9 years. The risk for rhythm disturbances remains. Regular cardiac evaluations should be continued, also after initially good response to ERT