129 GRANULOCYTE/MACROPHAGE COLONY STIMULATING FACTOR (GM-CSF) FOR TREATMENT IN GLYCOGEN STORAGE DISEASE TYPE IB

Abstract

Type Ib glycogen storage disease is caused by a defect in the glucose-6-phosphatase translocase of the microsomal glucose-6-phosphatase system. In addition to metabolic problems patients exhibit a predisposition for infections which is related to neutropenia. Various degrees of impairment of the neutrophil function have been observed including reduced chemotaxis and superoxide (O2−) production. In vitro, GM-CSF stimulates growth of myeloic progenitor cells and improves functions of mature neutrophils such as formation of oxygen radicals and chemotaxis. In clinical trials, GM-CSF has been shown to increase the neutrophil count in a dose-dependent manner.A 13 year old girl with type Ib glycogen storage disease, inflammatory bowel disease (resembling Crohn's disease), and obstinate neutropenia (neutrophil counts below 500/μl) sufferd from severe oral mucosal lesions. The girl was treated with human recombinant GM-CSF at a daily dose of 250 μg/m2 subcutaneously during a 2 week course with the parents' informed consent. From the third day of treatment the neutrophil count increased continuously from 216/μl to 6052/μl at day 14. At the same time, normal superoxide production was measured in the isolated granulocytes activated by PMA or zymosan. Oral ulcers resolved completely. Except for some painful hyperemic areas at the sites of injections no side effects appeared. After GM-CSF administration was discontinued leucocyte counts decreased to pre-treatment levels within 7 days.From the results of this limited clinical trial we conclude that GM-CSF can increase the neutrophil count and normalize specific granulocyte functions in glycogen storage disease Ib. GM-CSF might be of clinical benefit in managing severe inflammatory complications in neutropenic patients with this disorder.