RESUMO
Mucopolysaccharidoses (MPS) are genetically determined diseases, leading to a deficiency of enzymes in the glycosaminoglycan (GAG) degradation pathway. The accumulation of GAG occurs in connective tissue in various organs and systems of the body, including the larynx, trachea, and bronchi. Respiratory symptoms are common and severe in these patients, and respiratory disease is a frequent cause of death. A cross-sectional study with flexible bronchoscopy was conducted in 30 MPS patients (6 MPS I, 8 MPS II, 2 MPS III, 3 MPS IV-A, and 11 MPS VI). Only four patients (13.33%) had a normal airway; nine (30%) had mild to moderate disease, 12 (40%) moderate to severe, and five patients (16.67%) had severe disease. Of particular interest, neuronopathic MPS II had the largest proportion of tracheostomized patients who died due to respiratory complications; in MPS IV-A, all patients had significant tracheobronchial deformity with associated tracheomalacia, despite lacking laryngeal involvement. Laryngotracheobronchial disease (LTBD) was associated to longer disease history and was significantly more severe in older patients. Longer use of enzyme replacement therapy did not prevent the progression of LTBD, although the age of therapy introduction may be a crucial factor in lower airway involvement.
RESUMO
BACKGROUND: Enzyme replacement therapy (ERT) with laronidase (recombinant human α-L-iduronidase, Aldurazyme®) is indicated for non-neurological signs and symptoms of mucopolysaccharidosis type I (MPS I). The approved laronidase dose regimen is weekly infusions of 0.58mg/kg, however, patients and caregivers may have difficulty complying with the weekly regimen. We examined clinical outcomes, tolerability, compliance, and satisfaction in a series of patients who switched to every other week infusions. METHODS: This multinational, retrospective, chart review case series analyzed data from 20 patients who had undergone ERT with laronidase 0.58mg/kg weekly for more than one year, and who then switched to 1.2mg/kg every other week. RESULTS: The majority of patients had attenuated MPS I phenotypes (9 with Hurler-Scheie and 8 with Scheie syndromes) and 3 patients had severe MPS I (Hurler syndrome). Most patients presented with organomegaly (17/20), umbilical and/or inguinal hernia (16/20), cardiac abnormalities (17/20), musculoskeletal abnormalities (19/20), and neurological and/or developmental deficits (15/20). Following laronidase treatment, signs stabilized or improved. No deterioration or reversal of clinical outcome was noted in any patient who switched from the weekly dose of 0.58mg.kg to 1.2mg/kg every other week. There were no safety issues during the duration of every other week dosing. Patient compliance and satisfaction with the dosing regimen were greater with every other week dosing than weekly dosing. CONCLUSIONS: An alternative dose regimen of 1.2mg/kg laronidase every other week was well tolerated and clinically similar to the standard dose for patients who were stabilized with weekly 0.58 mg/kg for one year or more. When an individualized approach to laronidase therapy is necessary, every other week dosing may be an alternative for patients with difficulty receiving weekly infusions.
