Applying the functional independence measure to the assessment of patients with mucopolysaccharidosis / Test de medida de independencia funcional en la evaluación de pacientes con mucopolisacaridosis

Abstract Objective: To assess the functional independence of a group of patients with mucopolysaccharidosis using the Functional Independence Measure as a tool that accomplishes this purpose. Methods: This is a cross-sectional study of patients with mucopolysaccharidosis. Our data was collected between June 2015 and July 2016. In addition to history of present illness and physical examination each study participant was asked to answer a questionnaire to specifically evaluate their functional independence using the functional independence measure. the internal consistency of the functional independence measure was assessed using Cronbach's alpha coefficient. Results: We collected data on 20 patients with mucopolysaccharidosis. The average age was 10.8 (8.67-13.03) years, the average weight was 23.6 (19.91-27.37) kg and the average height was 1 (0.83-1.17) m. The most prevalent type of mucopolysaccharidosis in the study was type VI (n= 14). The average total functional independence measure score was 104.4 (97.61-111.19), the average for the mobility domain was 73.50 (68.22-78.78) and the average for the cognitive function domain was 30.90 (28.68-33.13). The internal consistency of the entire questionnaire was 0.859, with values of 0.966 for the mobility domain and 0.624 for the cognitive function domain. Conclusion: The lowest functional independence measure scores were obtained in the following sub-domains: self-care, locomotion and cognitive function. The functional independence measure questionnaire demonstrated internal consistency for the evaluation of functional independence in patients with mucopolysaccharidosis, being able to value all the affected sub-domains separately.

Resumen Objetivo: Evaluar la independencia funcional de un grupo de pacientes con mucopolisacaridosis utilizando la Medida de Independencia Funcional como herramienta para lograr este propósito. Métodos: Este es un estudio transversal de pacientes con mucopolisacaridosis. Nuestros datos se recopilaron entre junio de 2015 y julio de 2016. Además de la historia de la enfermedad actual y el examen físico, se pidió a cada participante del estudio que respondiera un cuestionario para evaluar específicamente su independencia funcional utilizando la Medida de Independencia Funcional. la consistencia interna de la Medida de Independencia Funcional se evaluó mediante el coeficiente alfa de Cronbach. Resultados: Recopilamos datos de 20 pacientes con mucopolisacaridosis. La edad promedio fue de 10.8 (8.67-13.03) años, el peso promedio fue de 23.6 (19.91-27.37) kg y la altura promedio fue de 1 m (0.83-1.17). El tipo de mucopolisacaridosis más prevalente en el estudio fue el tipo VI (n= 14). El puntaje promedio de la medida de independencia funcional total fue 104.4 (97.61-111.19), el promedio para el dominio de movilidad fue 73.50 (68.22-78.78) y el promedio para el dominio de función cognitiva fue 30.90 (28.68-33.13). La consistencia interna de todo el cuestionario fue de 0.859, con valores de 0.966 para el dominio de movilidad y 0.624 para el dominio de función cognitiva. Conclusión: Las puntuaciones más bajas de la medida de independencia funcional se obtuvieron en los siguientes subdominios: autocuidado, locomoción y función cognitiva. El cuestionario de medida de independencia funcional demostró consistencia interna para la evaluación de la independencia funcional en pacientes con mucopolisacaridosis, pudiendo valorar todos los subdominios afectados por separado.

Audiometric evaluation in individuals with mucopolysaccharidosis

OBJECTIVES: To characterize the audiometric evaluation and acoustic immittance measures in different types of mucopolysaccharidosis. METHOD: Fifty-three mucopolysaccharidosis patients were evaluated. The classification consisted of type I (Hurler syndrome, Hurler-Scheie and Scheie syndrome), type II (Hunter syndrome), type III (Sanfilippo syndrome), type IV (Morquio syndrome), and type VI (Maroteaux-Lamy syndrome). Immittance audiometry and play or conventional threshold tone audiometry were used to obtain auditory thresholds and were chosen according to the patient's chronological age and ability to understand/respond to the procedure. The findings were analyzed using descriptive statistics and considering the recommendations for research involving human beings contained in Resolution CNE N° 466/2012. RESULTS: Fifty-one subjects (96.2%) had hearing loss, and the conductive type was the most frequent. Only two (3.8%) patients presented bilateral thresholds within normal limits, one with type IV mucopolysaccharidosis and the other with type VI. There were 11 individuals (20.8%) with mucopolysaccharidosis type I with mixed hearing loss, 9 (16.9%) individuals with type I with conductive hearing loss and 9 (16.9%) with type VI with conductive hearing loss. Mild hearing loss was most common (37.3%), followed by moderately severe hearing loss (36.3%). The type B tympanometric curve (80.4%) was the most frequent. CONCLUSIONS: Most of the individuals with mucopolysaccharidosis types I, II, III, IV and VI presented mixed or conductive hearing losses of mild to moderately severe degree, type B tympanograms and an absence of contralateral acoustic reflexes.

Mucopolisacaridosis: características clínicas, diagnóstico y de manejo / Mucopolysaccharidosis: clinical features, diagnosis and management

Las mucopolisacaridosis (MPS) son un grupo de enfermedades raras (huérfanas), de baja prevalencia, caracterizadas por la deficiencia de enzimas que participan en el metabolismo de glucosaminglucanos (GAG) a nivel lisosomal. Se caracteriza por acumulación de GAG intracelular, produciendo alteraciones de múltiples órganos y sistemas. Su diagnóstico se basa en el conocimiento de las manifestaciones clínicas, realizar el análisis bioquímico para identificar el tipo de GAG que se está acumulando y confirmar el tipo de enfermedad con la determinación enzimática correspondiente. Su identificación es fundamental para iniciar un tratamiento oportuno, teniendo en cuenta que actualmente existe manejo transdisciplinario y tratamiento de reemplazo enzimático para MPS I (síndrome de Hurler), MPS II (síndrome de Hunter), MPS IV (síndrome de Morquio) y MPS VI (síndrome de Maroteaux-Lamy). En esta revisión se analizan cada uno de estos síndromes, su diagnóstico y tratamiento.

The mucopolysaccharidoses (MPS) are a group of rare (orphan) diseases, characterised by a deficiency of enzymes involved in the metabolism of glycosaminoglycans (GAGs) at lysosomal level. When there is a deficiency of a particular enzyme there is an accumulation of GAGs in the cells resulting in progressive cellular damage, which can affect multiple organ systems and lead to organ failure. Diagnosis is based on knowledge of the clinical manifestations, performing biochemical analyses to identify the type of GAG that is accumulating, and confirm the type of disorder with the corresponding enzymatic determination. Their identification is essential to initiate early treatment, taking into account that multidisciplinary management and enzyme replacement therapy is available for MPS I (Hurler syndrome), MPS II (Hunter syndrome), MPS IV (Morquio syndrome), and MPS VI (Maroteaux-Lamy syndrome. In this review, an analysis is made of each of these syndromes, as well as their diagnosis and treatment.

Avaliação da motricidade orofacial em pacientes com mucopolissacaridose: um estudo transversal / Evaluation of orofacial motricity in patients with mucopolysaccharidosis: a cross-sectional study

OBJETIVO: Caracterizar o sistema estomatognático e as funções estomatognáticas de pacientes com mucopolissacaridose. MÉTODOS: Estudo transversal e observacional de pacientes com mucopolissacaridose atendidos no ambulatório do Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre. O critério de inclusão foi a existência de diagnóstico bioquímico ou molecular de qualquer tipo de mucopolissacaridose e a concordância em participar do estudo mediante assinatura do termo de consentimento livre e esclarecido. Foram avaliados 78 pacientes através de anamnese e exame físico fonoaudiológicos. RESULTADOS: Alterações em pelo menos um item de cada estrutura do sistema estomatognático ou função estomatognática foram encontradas em todos os pacientes que permitiram a avaliação de ambos estes itens do exame físico (n = 76/78). As estruturas e funções mais frequentemente comprometidas foram, respectivamente, a arcada dentária e a língua e a deglutição e a mastigação. A única diferença estatisticamente significativa encontrada entre os tipos de mucopolissacaridose envolveu a posição habitual da língua entre os dentes (mais frequente na mucopolissacaridose VI). Entre os pacientes com mucopolissacaridose I, II ou VI submetidos ou não à terapia de reposição enzimática, foi encontrada diferença estatisticamente significativa no modo oral de respiração (mais frequente no grupo sem terapia de reposição enzimática). CONCLUSÕES: Alterações dos sistemas e funções estomatognáticas são prevalentes em indivíduos com mucopolissacaridose, mesmo na vigência de terapia de reposição enzimática. Tal achado sugere que o acompanhamento fonoterápico tenha papel importante no plano de tratamento desse grupo de doenças, hipótese que deve ser confirmada por estudos adicionais.

OBJECTIVE: To characterize the stomatognathic system and stomatognathic functions in patients with mucopolysaccharidosis. METHODS: Cross-sectional and observational study of patients with mucopolysaccharidosis seen at the outpatient clinic at the Medical Genetics Service of Hospital de Clínicas de Porto Alegre. The inclusion criteria were the existence of a biochemical or molecular diagnosis of any type of mucopolysaccharidosis and the agreement to participate in the study by signing an informed consent form. Seventy-eight patients were evaluated through phonoaudiological anamnesis and physical exam. RESULTS: Alterations in at least one item of each structure of the stomatognathic system or stomatognathic function were found in all patients who allowed evaluation of both items on physical examination (n = 76/78). The most frequently compromised structures and functions were respectively the dental arch and the tongue, swallowing and mastication. The only statistically significant difference found between types of mucopolysaccharidosis involved the habitual position of the tongue between the teeth (most frequent in mucopolysaccharidosis VI). Among patients with mucopolysaccharidosis I, II or VI who underwent enzyme replacement therapy or not, there was statistically significant difference in oral breathing mode (more frequent in the group without enzyme replacement therapy). CONCLUSIONS: Alterations in stomatognathic systems and functions are prevalent among individuals with mucopolysaccharidosis, even if enzyme replacement therapy is administered. Such finding suggests that speech therapy follow-up plays a major role in the treatment plan of this group of diseases; this hypothesis should be confirmed by additional studies.

Las mucopolisacaridosis / The mucopolysaccharidosis

Las mucopolisacaridosis (MPS) son errores innatos del metabolismo de los glicosaminoglicanos (GAG), que ocurren por déficit de alguna de las enzimas que degradan estas moléculas en los lisosomas. Esto conduce al depósito intralisosomal progresivo de GAG en diferentes tejidos, lo que explica el carácter multistémico de estas patologías. Las MPS, se presentan con una frecuencia aproximada de 1 caso en 10.000 a 25.000 recién nacidos vivos y son de herencia autosómica recesiva, salvo la MPS II o enfermedad de Hunter, que se hereda ligada al cromosoma X. Las características clínicas más frecuentes de las MPS son la presencia de rasgos faciales toscos, macrocefalia, opacidades corneales, disostosis múltiple, talla baja, valvulopatía mitroaórtica, hepatoesplenomegalia, hernias umbilical e inguinales, con o sin retraso del desarrollo sicomotor y con un deterioro neurológico progresivo. Salvo para las formas menos severas de MPS I, hasta ahora no hay un tratamiento efectivo para estas patologías, por lo que el daño sistémico progresivo produce la muerte entre los fines de la primera y de la cuarta década de la vida. En esta revisión se discuten las características clínicas de las MPS con las particularidades de cada fenotipo, el modo de confirmar el diagnóstico y los avances recientes en su tratamiento.

Clinical and laboratorial study of 19 cases of mucopolysaccharidoses

The mucopolysaccharidoses (MPS) are a heterogeneous group of inborn errors of lysosomal glycosaminoglycan (GAG) metabolism. The importance of this group of disorders among the inborn errors of metabolism led us to report 19 cases. METHOD: We performed clinical, radiological, and biochemical evaluations of the suspected patients, which allowed us to establish a definite diagnosis in 19 cases. RESULTS: Not all patients showed increased GAG levels in urine; enzyme assays should be performed in all cases with strong clinical suspicion. The diagnosis was made on average at the age of 48 months, and the 19 MPS cases, after a full clinical, radiological, and biochemical study, were classified as follows: Hurler -- MPS I (1 case); Hunter -- MPS II (2 cases); Sanfilippo -- MPS III (2 cases); Morquio -- MPS IV (4 cases); Maroteaux-Lamy -- MPS VI (9 cases); and Sly -- MPS VII (1 case). DISCUSSION: The high relative frequency of Maroteaux-Lamy disease contrasts with most reports in the literature and could express a population variability

El laboratorio clínico en el abordaje diagnóstico de las mucopolisacaridosis: presentación de un caso / Mucopolysaccharidoses diagnosis and clinic laboratory

Las mucopolisacaridosis son un grupo de alteraciones genéticas clasificadas dentro de los "Errores Innatos del Metabolismo" (EIM). Estos EIM son informados por varios autores con una incidencia baja (de 1:5000 a 1:320000 nacidos vivos). Sin embargo pueden ser más frecuentes de lo comunicado en la literatura, sobre todo cuando se tienen presentes como causa de enfermedad y son aplicados los estudios de escrutinio neonatal actualmente accesibles. Se detallan algunos de los análisis de laboratorio utilizados para su diagnóstico, y se describe brevemente un caso de mucopolisacaridosis infantil, que resalta la importancia del diagnóstico precoz mediante la aplicación de métodos sencillos. Se sugiere implementar y aplicar estos procedimientos en todo laboratorio clínico, para apoyar el diagnóstico oportuno de dichos desórdenes genéticos