Management of mucopolysaccharidosis type I using enzyme replacement therapy: Egyptian experience

Abstract Background Mucopolysaccharidosis type I (MPS I) is a known autosomal recessive lysosomal-storage disorder. The disease is caused by a deficiency of the alpha-L-iduronidase (IDUA) enzyme, accumulating the glycosaminoglycans (GAGs) in body organs and a wide phenotypic spectrum. Aim of the work: Herein, we report our experience, at the NRC, of enzyme replacement therapy (ERT) for MPS type I patients to assess the challenges faced for further improvement of the process. Patients and methods The diagnosis of MPS type 1 was based on clinical examination, radiological findings, quantitation of GAGs in urine, electrophoretic separation of GAGs and alpha-L-iduronidase enzyme assays. After ministry approval to start ERT, thirty-eight MPS-I patients were examined at presentation and assessed for one year throughout ERT to evaluate its effect and safety. Initial and follow-up of quantitation of GAGs in urine, echocardiography, pulmonary function tests and abdominal ultrasound were done for cooperative compliant patients. Results Clinical and radiological examinations confirmed the diagnosis of MPS-1. Follow-up of patients after one year of ERT revealed a significant decrease in the size of the liver and spleen, an improvement in respiratory function tests, a stationary course of cardiac problems and a reduction in total urinary GAG levels. We faced the challenges of late diagnosis, long procedures to get approval for ERT, thus leading to delayed ERT initiation in addition to irregular ERT courses due to delay in treatment renewal and difficulties in patient’s transportation from far governorates. Laronidase was generally well tolerated apart from mild infusion-related adverse reactions. In conclusion: ERT is an effective line of management of MPS-I patients. Early diagnosis, less complicated process for treatment approval and efficient multidisciplinary centers able to provide ERT and hematopoietic stem cell transplantation (HSCT) are recommended.