Clinical features and health-related quality of life in adult patients with mucopolysaccharidosis IVA: the Spanish experience

Orphanet Journal of Rare Diseases

Guillem Pintos-Morell¹  Marc Moltó-Abad¹  David Moreno-Martínez²  Ricardo Gil Sánchez³  Elisenda Cortès-Saladelafont⁴  Encarna Guillén-Navarro⁵  María Juliana Ballesta-Martínez⁵  Mónica A. López Rodríguez⁶  Elena Arranz Canales⁷  Montserrat Morales Conejo⁷  María Luz Couce⁸  Salvador García Morillo⁹  María Teresa García-Silva^1,10  Elena Martín-Hernández^1,10  Pilar Quijada-Fraile^1,10  Javier Blasco-Alonso^1,11 

[1] Division of Rare Diseases, Reference Center for Hereditary Metabolic Disorders (CSUR, MetabERN, MetabXUEC), University Hospital Vall d’Hebron, Barcelona, Spain;Division of Rare Diseases, Reference Center for Hereditary Metabolic Disorders (CSUR, MetabERN, MetabXUEC), University Hospital Vall d’Hebron, Barcelona, Spain;Lysosomal Storage Disorders Unit, The Royal Free Hospital NHS Foundation Trust and University College London, London, UK;Hospital Universitario La Fe, Valencia, Spain;Inborn Errors of Metabolism and Paediatric Neurology Unit, Paediatric Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain;Sección de Genética Médica, Hospital Clínico Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Universidad de Murcia, Murcia, Spain;CIBERER-ISCIII, Madrid, Spain;Servicio de Medicina Interna, CSUR Enfermedades Metabólicas Hereditarias, Hospital Universitario Ramón y Cajal, Madrid, Spain;Servicio de Medicina Interna, CSUR Enfermedades Metabólicas, MetabERN, Instituto de Investigación Sanitaria Hospital 12 de octubre (imas12), Hospital Universitario 12 de Octubre, Madrid, Spain;Unidad de Diagnóstico y Tratamiento de Enfermedades Metabólicas Hereditarias, Hospital Clínico Universitario de Santiago, IDIS, MetabERN, CIBERER, Santiago de Compostela, Spain;Unidad de Enfermedades Autoinmunes y Minoritarias, Servicio de Medicina Interna, Hospital Virgen del Rocío, Sevilla, Spain;Unidad de Enfermedades Mitocondriales y Enfermedades Metabólicas Hereditarias, Servicio de Pediatría, Hospital Universitario 12 de Octubre, CSUR Enfermedades Metabólicas, MetabERN, Instituto de Investigación Sanitaria Hospital 12 de octubre (imas12), CIBERER, Madrid, Spain;Unidad de Gastroenterología y Nutrición Infantil, Grupo IBIMA Multidisciplinar Pediátrico, Hospital Regional Universitario de Málaga, Málaga, Spain;

关键词: Elosulfase alfa;    Health-related quality of life;    Mobility;    Morquio A syndrome;    Mucopolysaccharidosis IVA;   

DOI  :  10.1186/s13023-021-02074-y

来源: Springer

【 摘 要 】

BackgroundMucopolysaccharidosis (MPS) IVA or Morquio A syndrome is a progressive and disabling disease characterized by a deficiency of the enzyme N-acetylgalactosamine-6-sulphate sulphatase. Its clinical presentation is very heterogeneous and poorly understood in adults.The aim of this study was to describe the clinical manifestations of MPS IVA in adult patients in Spain and to assess their health-related quality of life (HRQoL).ResultsThirty-three patients from nine reference centres participated in the study. The median age was 32 (interquartile range [IQR]: 20.5–40.5) years. The phenotype was classical in 54.5% of patients, intermediate in 33.3% of patients, and non-classical in 12.1% of patients. The most common clinical manifestation was bone dysplasia, with a median height of 118 (IQR: 106–136) cm. Other frequent clinical manifestations were hearing loss (75.7%), ligamentous laxity (72.7%), odontoid dysplasia (69.7%), limb deformities that required orthopaedic aids (mainly hip dysplasia and genu valgus) (63.6%), and corneal clouding (60.6%). In addition, 36.0% of patients had obstructive sleep apnoea/hypopnoea syndrome and 33.3% needed non-invasive ventilation. Cervical surgery and varisation osteotomy were the most common surgical interventions (36.4% each). Almost 80% of patients had mobility problems and 36.4% used a wheelchair at all times. Furthermore, 87.9% needed help with self-care, 33.3% were fully dependent, and 78.8% had some degree of pain. HRQoL according to the health assessment questionnaire was 1.43 (IQR: 1.03–2.00) in patients with the non-classical phenotype, but 2.5 (IQR: 1.68–3.00) in those with the classical phenotype. Seven patients were initiated on enzyme replacement therapy (ERT), but two of them were lost to follow-up. Lung function improved in four patients and slightly worsened in one patient. The distance achieved in the six-minute walk test increased in the four patients who could perform it. HRQoL was better in patients treated with elosulfase alfa, with a median (IQR) of 1.75 (1.25–2.34) versus 2.25 (1.62–3.00) in patients not treated with ERT.ConclusionsThe study provides real-world data on patients with MPS IVA. Limited mobility, difficulties with self-care, dependence, and pain were common, together with poor HRQoL. The severity and heterogeneity of clinical manifestations require the combined efforts of multidisciplinary teams.

【 授权许可】

CC BY