ENZYME REPLACEMENT TREATMENT IN TYPE-1 AND TYPE-3 GAUCHERS-DISEASE

The development of intravenous enzyme-replacement treatment for Gauche r's disease has changed life expectancy in cases without neurological involvement (type 1). The effects in patients with neurological involv ement are unknown. We treated 12 Italian patients, types 1 (9) and 3 ( 3), with intravenous alglucerase: 70-120 IU/kg per month for type 3 an d 30-60 IU/kg per month for type 1. Maintenance infusions were biweekl y in patients without neurological symptoms, whereas in one symptomati c type 3 patient, influsion was weekly. All patients improved; a resum ption of growth in children with growth retardation was observed and s pleen and liver reduced in size. In one type 3 patient, a bone callus formed during treatment and enabled the patient to walk. Laboratory te sts showed rapid increase of haemoglobin in anaemic patients, and a sl ower response in patients with thrombocytopaenia. In 4 patients there was temporary hypocalcaemia immediately after the beginning of treatme nt. Neurological symptoms were present in 1 of the type 3 patients, an d electroencephalogram was abnormal in another. After 2 years of treat ment, the patient with symptoms showed an improvement of psychomotor s kills and of IQ from 50 to 60. Genotype analysis showed a high frequen cy of the 1448C mutation (54.5%). The 9 patients carrying this allele came from Italian regions which in the past had been invaded from nort h Europe and Scandinavia. Enzyme replacement in Gaucher's type 1 can a lso be effective at low doses and even with a 2-week interval between infusions. This makes treatment cheaper, and reduces hospital stay for patients.