Enzyme replacement therapy for mucopolysaccharidosis II from 3 months of age: a 3-year follow-up

ABSTRACTAim: We present a 3-year follow-up of a boy with mucopolysaccharidosis type II(MPS II) who had idursulfase therapy initiated at the age of 3 months and compare hisclinical course to his healthy twin brother. Methods: Detailed anthropometric features, ultrasound studies of liver and spleenvolumes, echocardiography and audiological examinations, psychological tests, joint rangeof motion (ROM) and skeletal radiographs were monitored. Results: After 3 years of treatment, the patient has not developed any clinical mani-festationsofMPSII.Hedidnotdevelopcoarsefacialfeatures,jointdisease,ororganomegaly,andhiscardiacfunctionremainednormal.Therewerenopronouncedsignsofdysostosismultiplexonradiographs.TheonlydifferencewhencomparedwithhishealthytwinbrotherwaslowerIQ(Termann-Merrill98vs.118)andmilddeformityofonevertebrae. Conclusion: Our study suggests that early initiation of enzyme replacement therapymay significantly slow or prevent the development of irreversible disease manifestationsand therefore modify the natural history of MPS II.INTRODUCTIONMucopolysaccharidosis type II (MPS II, Hunter syndrome,OMIM #309900) is an X-linked, recessive, lysosomal stor-age disorder caused by a deficiency of iduronate-2-sulfatase(IDS, EC 3.1.6.13) (1). Deficient enzyme activity leads towidespread accumulation of the glycosoaminoglycans(GAG) dermatan and heparan sulphate, ultimately resultingin a progressive multisystem disease with respiratory, car-diac, skeletal and, in the majority of cases, neurologicalmanifestations (1–3).Enzyme replacement therapy (ERT) with recombinanthuman IDS (Elaprase; Shire Human Genetic Therapies,Inc, Cambridge, MA, USA) has been shown to be a safe andeffective therapy across a wide range of ages and diseaseseverity; improving respiratory function, joint mobility,6-min walk test and quality of life (4–6).Experience of treating children under the age of5 years with idursulfase is rather limited (6). The factremains that most patients are diagnosed symptomati-cally, unless, as in this case, a younger asymptomatic sib-ling is diagnosed with the disease because of an olderaffected sibling.Here, we present the case of a boy with MPS II whostarted idursulfase treatment presymptomatically at the age