Imiglucerase low-dose therapy for paediatric Gaucher disease: a long-term cohort study

Gaucher disease is the most common lysosomal storage disorder caused by the insufficiency of the lysosomal enzyme, glucocerebrosidase. This deficiency results in absent or inefficient conversion of glucocerebroside (a membrane lipid) to ceramide and glucose. Accumulation of glucocerebroside occurs primarily in macrophage lysosomes (i.e. monocytes and macrophages) during phagocytic degradation of red blood cells. Clinical symptoms arise due to the displacement of normal cells by lipid-engorged Gaucher cells. Enzyme replacement therapy (ERT) targets the macrophage system and has been shown to be successful in the treatment of type 1 Gaucher disease in adults and children. ERT (60 U/kg) every 2 weeks decreases and often reverses organomegaly and haematological complications and improves quality of life for patients with type 1 Gaucher disease. The present study describes the course of 9 paediatric patients followed up for 2 - 10 years receiving low-dose imiglucerase therapy (+/- 10 U/kg every 2 weeks) for moderate to severe type 1 Gaucher disease. To evaluate the efficacy of low-dose imiglucerase therapy in paediatric Gaucher disease. Data were recorded at a single centre for 9 paediatric patients. Assessment of response included serial measurements of haemoglobin (Hb) concentrations, platelet count, angiotensin-converting enzyme (ACE) and total acid phosphatase (TAP) levels. Growth was assessed by serial determinations of body weight and height, plotted against standard growth charts. Organ size (liver and spleen) was measured clinically and also radiologically, where possible. In this low-dose imiglucerase treatment group: (i) there was a significant increase in Hb over time--normal Hb levels were achieved in 7 of the 9 patients after a mean of 3.7 years; (ii) platelet counts increased over time, reaching normal levels in 7 patients; (iii) there was a significant decrease in both ACE and TAP over time; (iv) heights and weights of the subjects increased significantly over time with treatment, normalising to the expected growth percentiles; and (v) organ size (liver and spleen) reduced with therapy in all patients measured. ERT with low-dose imiglucerase (+/- 10 U/kg/fortnight) ameliorates Gaucher disease-associated anaemia and thrombocytopenia. Low-dose ERT is effective and may be considered in resource-poor clinical situations when other alternatives are not available.