Background
• First described in two brothers by Dr Charles A. Hunter in 1917. | |
• Caused by deficient activity of the lysosomal enzyme iduronate-2-sulfatase (EC 3.1.6.13), which catalyses a step in the catabolism of the glycosaminoglycans (GAG) dermatan sulfate and heparan sulfate. The accumulation of these in tissues and organs throughout the body contributes to the chronic, progressive, multisystemic manifestations of MPS II [14, 15]. | |
• The initial clinical signs and symptoms typically emerge within the first few years of life and include recurrent respiratory infections, coarse facial features, joint stiffness, otitis media, hearing loss, umbilical/inguinal hernias, and hepatosplenomegaly [45]. | |
• The severity of the disease spans a broad range. For clinical purposes, patients are generally considered to fall into one of two categories according to the presence or absence of cognitive impairment. All patients will experience somatic disease manifestations, although progression may be slower in individuals without cognitive impairment [14, 15]. About two-thirds of patients will display progressive central nervous system involvement, initially resulting in learning impairment and abnormal behaviour, followed by the development of profound cognitive impairment [12]. |
Registry design and objectives
Primary endpoints | |
Safety of idursulfase • Occurrence of infusion-related reactions and other adverse events (including serious adverse events) • Immunogenicity, as determined by time to first positive antibody response (antibody level and isotype), antibody titre, isotype, and neutralizing antibodies Effectiveness of idursulfase • Urinary glycosaminoglycan levels • Growth parameters (height, weight, head circumference) • Distance walked in the 6-min walk test • Left ventricular mass index (calculated by echocardiography) • Pulmonary function (measured by forced expiratory volume in 1 s and forced vital capacity) • Liver and spleen size (as estimated by palpation) • Prevalence of cardiac- and pulmonary-related hospitalizations • Deaths (including age at death and cause of death) | |
Secondary endpoints | |
• Evaluation of the natural history of MPS II (based on the following signs and symptoms: hepatosplenomegaly, central nervous system involvement, skeletal involvement, and signs and symptoms of cardiac, pulmonary, and ear, nose, and throat involvement) • Evaluation of dosing of idursulfase (prescribed dose, administered dose, total infusion time, missed infusions, and reasons for missed infusions) • Scoring in five domains in the patient- and parent-reported versions of the HS-FOCUS questionnaire |