Basic research for the efficiency of enzyme therapy for glycogen storage disease type II (pompe disease)

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Glycogen storage disease type II (Pompe disease) is caused by deficiency of acid alpha-glucosidase resulting in accumulations of glycogen in multiple tissues. Some reports of enzyme therapy using recombinant human acid alpha-glucosidase (rhGAA) showed clinical improvement of infantile Pompe disease in a few cases, and production of anti-rhGAA antibody might reduce the effectiveness of rhGAA therapy.A two years old Japanese girl with Pompe disease had attended a year of international clinical trial of rhGAA and came back to Japan. We succeeded her enzyme therapy with rhGAA (Genzyme Japan). Her cardiac dysfunction was improving and a report from UK suggests no anti-rhGAA antibody production. We followed her clinical course and investigate genetic background to develop more efficient enzyme for enzyme replacement therapy.1. rhGAA therapy for Pompe disease.We injected rhGAA every two weeks to a Japanese three years old girl with Pompe disease with agreement of her parents. She was often suffered from respiratory infections and her enzyme injection was sometimes postponed by reasons of her infections or her parents' inconvenience. After over a month of postpone of injection, she was affected with severe pneumonia and required mechanical ventilation support and intensive care. She had recovered with injection of rhGAA and antibiotics, however she required trachecstomy and home oxygen therapy. She now takes injection every two weeks strictly and her cardiac function is almost normal.2. Acid alpha-glucosidase gene mutation analysis.We extracted DNA and total RNA from patient's skin fibroblast and human acid alpha-glucosidase gene cDNA was amplified by conventional RT-PCR technique. Sequence analysis of cDNA showed a missence mutation (796C>T), which was already reported as pathological mutation.3. Investigation about immunogensity of rhGAA.After following injection of rhGAA, our patient produced anti-rhGAA antibody. Our analysis of her immune function was normal.