title: Enzymatic replacement therapy for Hunter disease: Up to 9 years experience with 17 patients.
abstract: Hunter disease is an X-linked lysosomal storage disorder characterized by progressive storage of glycosaminoglycans (GAGs) and multi-organ impairment. The central nervous system (CNS) is involved in at least 50% of cases. Since 2006, the enzymatic replacement therapy (ERT) is available but with no effect on the cognitive impairment, as the present formulation does not cross the blood-brain barrier. Here we report the outcome of 17 Hunter patients treated in a single center. Most of them (11) started ERT in 2006, 3 had started it earlier in 2004, enrolled in the phase III trial, and 3 after 2006, as soon as the diagnosis was made. The liver and spleen sizes and urinary GAGs significantly decreased and normalized throughout the treatment. Heart parameters improved, in particular the left ventricular mass index/m(2) decreased significantly. Amelioration of hearing was seen in many patients. Joint range of motion improved in all patients. However, no improvement on respiratory function, eye, skeletal and CNS disease was found. The developmental quotient of patients with a CNS involvement showed a fast decline. These patients were no more testable after 6 years of age and, albeit the benefits drawn from ERT, their quality of life worsened throughout the years. The whole group of patients showed a consistent residual disease burden mainly represented by persistent skeletal disease and frequent need of surgery. This study suggests that early diagnosis and treatment and other different therapies which are able to cross the blood-brain barrier, might in the future improve the MPS II outcome.
authors.affiliation: Dept of Pediatrics, Fondazione MBBM, San Gerardo Hospital, Monza, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Parini
authors.affiliation: Dept of Internal Medicine, San Gerardo Hospital, Monza, Italy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Rigoldi
authors.affiliation: Dept of Rehabilitation Medicine San Gerardo Hospital, Monza, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Tedesco
authors.affiliation: Dept of Cardiology, San Gerardo Hospital, Monza, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Boffi
authors.affiliation: Dept of Pediatrics, Fondazione MBBM, San Gerardo Hospital, Monza, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Brambilla
authors.affiliation: Dept of Pediatrics, Fondazione MBBM, San Gerardo Hospital, Monza, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Bertoletti
authors.affiliation: Dept of Pediatrics, Fondazione MBBM, San Gerardo Hospital, Monza, Italy.
authors.forename: Agata
authors.initials: A
authors.lastname: Boncimino
authors.affiliation: Dept of Pediatric Ophthalmology, Niguarda Hospital, Milano, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Del Longo
authors.affiliation: Statistical Unit, Department of Preventive Medicine, University Milano Bicocca, Monza, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: De Lorenzo
authors.affiliation: Dept of Otholaryngology, San Gerardo Hospital, Monza, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Gaini
authors.affiliation: Dept of Orthopedics, San Gerardo Hospital, Monza, Italy.
authors.forename: Denise
authors.initials: D
authors.lastname: Gallone
authors.affiliation: Dept of Pediatrics, Fondazione MBBM, San Gerardo Hospital, Monza, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Gasperini
authors.affiliation: Dept of Neurosurgery, San Gerardo Hospital, Monza, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Giussani
authors.affiliation: Dept of Radiology, San Gerardo Hospital, Monza, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Grimaldi
authors.affiliation: Dept of Pediatric Neurology San Gerardo Hospital, Monza, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Grioni
authors.affiliation: Dept of Pediatrics, Fondazione MBBM, San Gerardo Hospital, Monza, Italy.
authors.forename: Pamela
authors.initials: P
authors.lastname: Meregalli
authors.affiliation: Dept of Pneumology, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Messinesi
authors.affiliation: Dept of Pediatrics, Fondazione MBBM, San Gerardo Hospital, Monza, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Nichelli
authors.affiliation: Dept of Otholaryngology, San Gerardo Hospital, Monza, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Romagnoli
authors.affiliation: Dept of Cardiology, San Gerardo Hospital, Monza, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Russo
authors.affiliation: Dept of Neurosurgery, San Gerardo Hospital, Monza, Italy.
authors.forename: Erik
authors.initials: E
authors.lastname: Sganzerla
authors.affiliation: Statistical Unit, Department of Preventive Medicine, University Milano Bicocca, Monza, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Valsecchi
authors.affiliation: Dept of Pediatrics, Fondazione MBBM, San Gerardo Hospital, Monza, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Biondi
keywords: 6MWT, Six minute walking test; BAER, Brainstem auditory evoked responses; CNS, Central nervous system; EF, Ejection fraction; ENT, Ear nose and throat; ERT; ERT, Enzyme replacement therapy; Enzymatic replacement therapy; GAGs, Glycosaminoglycans; HAQ, Health Assessment Questionnaire; Hunter disease; Hunter syndrome; I2S, Iduronate-2-sulfatase; Idursulfase; JROM, Joint range of motion; LVM/LVMI, Left ventricular mass/left-ventricular mass index; MDCT, Multidetector computed tomography; MPS II; MPS II, Mucopolysaccharidosis type II; MPS, Mucopolysaccharidosis; MRI, Magnetic resonance imaging; Mucopolysaccharidosis type II; QoL, Quality of Life; UAI, Upper airway infections