Hunter syndrome: Enzyme replacement therapy with idursulfase in 3 patients under 5 years of age in Argentina .

AMARTINO H; MARCHIONE D; PERICHON MG; RICHAUDEAU A; ROZENFELD PA; CAYSIALS A

Playa del Carmen, Mexico

Simposio; III Congreso Latinoamericano de Enfermedades Lisosomales; 2010

Background. The approval by FDA of idursulfase (ElapraseTM) as specific treatment for MPSII was based in a clinical trial with 2 primary endpoints: 6-minute walking test and changes in predicted FVC, parameters which per se excluded children less than 5 years of age. Therefore, safety and efficacy of idursulfase have not been established for infants and young pediatric patients. Considering the nature of this genetic progressive disease, very early start of treatment is thought to lead to better outcomes. Aim: To report our experience with idursulfase replacement therapy in 3 children with MPS II under 5 years of age. Case 1: Male, 1 yo, diagnosed at neonatal period (familial history of MPS II). Urine GAGSa: dermatan y heparan sulfate. 3 months:  Iduronate sulfatase activity in leukocyites 0,1 nmol/h/ mg (NR: 5,9-19,8). Mutation: c683C>A/p.P228Q. Initial symptoms: hepatosplenomegaly and intermittent otitis media/upper respiratory infections. ERT was started at 14 months. Case 2:  Male, cousin of case 1, diagnosed at 4y 9/12m. Iduronate sulfatase activity:  0,4 nmol/h/ mg. He presented coarse face, hypoacusia, organomegaly, sleep disturbances and dysostosis. ERT started at 5 y 2/12m Case 3: Male, 4 y.o, diagnosed at 16 months. Iduronate sulfatase 0,1 nmol/h/mg. Mutation: p.R468Q. Initial symptoms: Gibbus, coarse face and hepatomegaly since 9m. ERT started at age 30m Results Idursulfase has been provided in standart dosing (0,5 mg/kg/step-wise over 3 hours, weekly) for a total of 32 months for case 1 and 2 and 24 consecutive months for case 3.Case 3 developed skin rush from 4th to 7th infusions, which resolved by decreasing the infusion rate. During 7th infusion he presented mild respiratory distress which lead to stop infusion. Antihistaminic pre-treatment was added with good response. No other adverse event was noticed. Subsequently, rate of infusion was increased to the regular schedule over time. Response to therapy was noted by decreased urinary glycosaminoglycans (GAGs) excretion until normalization in all the cases. All the patients showed decreased rate of annual respiratory events and improvement of organomegaly. Conclusions: We conclude that idursulfase was effective and safe in these 3 patients under 5 years of age. This experience adds evidence to previous reports from other countries. Long-term studies with bigger number of patients will be necessary to accurately evaluate safety and efficacy in this special population.