Monitoring and integrated care coordination of patients with alpha-mannosidosis: A global Delphi consensus study.

INTRODUCTION: Current literature lacks consensus on initial assessments and routine follow-up care of patients with alpha-mannosidosis (AM). A Delphi panel was conducted to generate and validate recommendations on best practices for initial assessment, routine follow-up care, and integrated care coordination of patients with AM. METHODS: A modified Delphi method involving 3 rounds of online surveys was used. An independent administrator and 2 nonvoting physician co-chairs managed survey development, anonymous data collection, and analysis. A multidisciplinary panel comprising 20 physicians from 12 countries responded to 57 open-ended questions in the first survey. Round 2 consisted of 11 ranking questions and 44 voting statements. In round 3, panelists voted to validate 60 consensus statements. The panel response rate was ≥95% in all 3 rounds. Panelists used 5-point Likert scales to indicate importance (score of ≥3) or agreement (score of ≥4). Consensus was defined a priori as ≥75% agreement with ≥75% of panelists voting. RESULTS: Consensus was reached on 60 statements, encompassing 3 key areas: initial assessments, routine follow-up care, and treatment-related follow-up. The panel agreed on the type and frequency of assessments related to genetic testing, baseline evaluations, quality of life, biochemical measures, affected body systems, treatment received, and integrated care coordination in patients with AM. Forty-nine statements reached 90% to 100% consensus, 8 statements reached 80% to 85% consensus, and 1 statement reached 75% consensus. Two statements each reached consensus on 15 baseline assessments to be conducted at the initial follow-up visit after diagnosis in pediatric and adult patients. CONCLUSION: This is the first Delphi study providing internationally applicable, best-practice recommendations for monitoring patients with AM that may improve their care and well-being.

Manejo clínico odontológico de un paciente con mucopolisacaridosis tipo III. (Síndrome de Sanfilippo) / Dental clinical management of a patient with type III mucopolysaccharidosis (Sanfilippo syndrome)

El síndrome de Sanfilippo (mucopolisacaridosis tipo III) es un trastorno lisosomal causado por un defecto en el catabolismo del sulfato de heparano. La mucopolisacaridosis tipo III es el tipo más común de todas las mucopolisacaridosis. La base patógena de la enfermedad consiste en el almacenamiento de sustrato no degradado en el sistema nervioso central. El deterioro cognitivo progresivo que resulta en demencia y anomalías de comportamiento son las principales características clínicas del síndrome de Sanfilippo. La mucopolisacaridosis tipo III puede diagnosticarse erróneamente como otras formas de retraso del desarrollo, trastorno por déficit de atención/hiperactividad y trastornos del espectro autista, debido a la falta de síntomas somáticos y a la presencia de formas leves y atípicas de la enfermedad. Los pacientes con síndrome de Sanfilippo pueden tener niveles de glicosaminoglicanos en la orina comparativamente bajos, lo que da como resultado un ensayo urinario falso negativo. El diagnóstico definitivo se realiza mediante un ensayo enzimático en leucocitos y fibroblastos cultivados. Actualmente no existe un tratamiento eficaz de la mucopolisacaridosis tipo III, aunque las investigaciones en curso sobre el gen, la reducción de sustratos y las terapias de reemplazo de enzimas intratecales esperan obtener un método curativo para alterar el daño devastador del sistema nervioso central en un futuro próximo. El tratamiento odontológico de los pacientes con MPS-III requiere colaboración multidisciplinar, siendo de vital importancia el mantenimiento y controles periódicos, sobre todo en fases tempranas de la enfermedad. En estados avanzados se requerirá el uso de la anestesia general o la sedación profunda para dichos tratamientos, lo que supondrá un enorme reto para el profesional. (AU)

Sanfilippo syndrome (mucopolysaccharidosis type III) is a lysosomal disorder caused by a defect in the catabolism of heparan sulfate. Mucopolysaccharidosis type III is the most common type of mucopolysaccharidosis. The pathogenic basis of the disease consists of the storage of non-degraded substrate in the central nervous system. The progressive cognitive deterioration that results in dementia and behavioral abnormalities are the main clinical features of Sanfilippo syndrome. Mucopolysaccharidosis type III can be misdiagnosed as other forms of developmental delay, attention deficit/hyperactivity disorder and autistic spectrum disorders due to the lack of somatic symptoms, the presence of mild and atypical forms of the disease. Patients with Sanfilippo syndrome may have comparatively low glycosaminoglycan levels in the urine, resulting in a falsenegative urinary test. The definitive diagnosis is made by an enzymatic assay in cultured leukocytes and fibroblasts. There is currently no effective treatment for mucopolysaccharidosis type III, although ongoing research on the gene, substrate reduction and intrathecal enzyme replacement therapies hope to obtain a curative method to alter the devastating damage of the central nervous system in the future next. The dental treatment of patients with MPS-III requires multidisciplinary collaboration, being of vital importance the maintenance and periodic controls especially in early phases of the disease. In advanced stages, the use of general anesthesia or deep sedation will be required for dental procedures, which will be a huge challenge for the professional. (AU)

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

BACKGROUND: Mucopolysaccharidosis (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). RESULTS: Thirty-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. CONCLUSIONS: The 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.

Consideraciones bucodentales en pacientes con Síndrome de Morquio / Dental considerations of the morquio síndrome

La mucopolisacaridosis tipo IV (MPS-IV) también conocida como enfermedad de Morquio en recuerdo del pediatra uruguayo Luis Morquio que la describió por primera vez, es una enfermedad congénita causada por la deficiencia de la enzima N-acetilgalactosamina 6 sulfatasa o de la enzima B-Galactosidasa. Estas anomalías enzimáticas tienen como consecuencia que se acumulen en diferentes tejidos del organismo cantidades elevadas de mucopolisacaridos. En la bibliografía se describe con detalle los defectos del esmalte que presentan los pacientes diagnosticados del síndrome de Morquio. Estos defectos son una característica aparentemente constante en la enfermedad y, por lo tanto, hace necesaria las visitas al odontólogo para su control evitándose problemas mayores. Dichos defectos consisten en un esmalte anormalmente delgado, que es áspero debido a los numerosos hoyos diminutos y a una superficie irregular. La delgadez del esmalte da como resultado una forma alterada y decoloración de los dientes que, añadido a los diastemas interdentales, provocan alteraciones en la oclusión. Aparte de estos defectos, el esmalte es histológicamente normal y tiene una du-reza y radiodensidad normales. El trata-miento odontológico de los pacientes con MPS-IV requiere colaboración multidisciplinar, debido a que las manifestaciones orales de la enfermedad pueden aparecer a cualquier edad, resultando en ocasiones tedioso para el paciente y complicado para el profesional. Especial mención merecen las terapias utilizadas como trata-miento sintomático de la enfermedad, así como el manejo de la vía aérea en el caso de intervenciones bajo anestesia general o sedación para tratar ciertas patologías del territorio bucomaxilodental

Mucopolysaccharidosis type IV (MPS-IV) also known as Morquio’s disease in memory of the Uruguayan pediatrician Luis Morquio who described it for the first time, is a congenital disease caused by the deficiency of the enzyme N-acetylgalactosamine 6 sulfatase or enzyme B -Galactosidase. These enzymatic anomalies result in high amounts of mucopolysaccharides accumulating in different tissues of the organism. The enamel defects presented by patients diagnosed with Morquio syndrome are described in detail in the bibliography. These defects are an apparently constant feature in the disease and, therefore, make visits to the dentist necessary for their control, avoiding major problems. These defects consist of an abnormally thin enamel that is rough due to numerous tiny holes and an irregular surface. The thinness of the enamel results in an altered form and discoloration of the teeth, which added to the interdental diastemas, cause alterations in the occlusion. Apart from these defects, the enamel is histologically normal and has a normal hardness and radiodensity.Dental treatment of patients with MPS-IV requires multidisciplinary collaboration, because the oral manifestations of the disease can appear at any age, being sometimes tedious for the patient and complicated for the professional. Special mention should be made of the therapies used as a symptomatic treatment of the disease, as well as the management of the airway in the case of interventions under general anesthesia or sedation to treat certain pathologies of the bucomaxillodental territory