Hematopoietic Stem Cell Transplantation for Mucopolysaccharidoses: Past, Present, and Future.

Allogenic hematopoietic stem cell transplantation (HSCT) has proven to be a viable treatment option for a selected group of patients with mucopolysaccharidoses (MPS), including those with MPS types I, II, IVA, VI, and VII. Early diagnosis and timely referral to an expert in MPS are critical, followed by a complete examination and evaluation by a multidisciplinary team, including a transplantation physician. Treatment recommendations for MPS are based on multiple biological, sociological, and financial factors, including type of MPS, clinical severity, prognosis, present clinical signs and symptoms (disease stage), age at onset, rate of progression, family factors and expectations, financial burden, feasibility, availability, risks and benefits of available therapies such as HSCT, enzyme replacement therapy (ERT), surgical interventions, and other supportive care. International collaboration and data review are critical to evaluating the therapeutic efficacy and adverse effects of HSCT for MPS. Collaborative efforts to assess HSCT for MPS have been ongoing since the first attempt at HSCT in a patient with MPS reported in 1981. The accumulation of data since then has made it possible to identify early outcomes (ie, transplantation outcomes) and long-term disease-specific outcomes resulting from HSCT. The recent identification of predictive factors and the development of innovative regimens have significantly improved the outcomes of both engraftment failure and transplantation-related mortality. Assessment of long-term outcomes has considered a variety of factors, including type of MPS, type of graft, age at transplantation, and stage of disease progression, among others. Studies on long-term outcomes are considered a key factor in the use of HSCT in patients with MPS. These studies have shown the effects and limitations of HSCT on improving disease manifestations and quality of life. In this review, we summarize the efficacy, side effects, risks, and cost of HSCT for each type of MPS.

Crianças e adolescentes com mucopolissacaridoses: saúde bucal e senso de coerência materno / Children and adolescents with mucopolysaccharidosis: oral health status and mother´s sense of coherence

As mucopolissacaridoses (MPS) são um grupo de doenças hereditárias causadas pela falta de enzimas lisossomais específicas responsáveis pela degradação de glicosaminoglicanos (GAG). Por meio do Senso de Coerência (SOC), é possível compreender a razão de algumas pessoas adoecerem após a ocorrência de uma situação estressante e outras não. Este estudo objetivou testar a associação entre o Senso de Coerência Materno (SOC) Materno e a presença de MPS, bem como entre o SOC Materno e a saúde bucal de crianças/adolescentes com e sem MPS. Foi realizado um estudo transversal pareado, com uma amostra de 58 crianças/adolescentes, sendo 29 com MPS e 29 sem MPS, entre 3 e 21 anos, e suas respectivas mães. Os participantes dos dois grupos foram pareados por sexo e idade. Os dados foram coletados em uma das clínicas da Faculdade de Odontologia da Universidade Federal de Minas Gerais, localizada na cidade de Belo Horizonte, região sudeste do Brasil. As crianças/adolescentes com e sem MPS, bem como as respectivas mães, foram selecionadas em um hospital universitário. As mães que concordaram em participar do estudo responderam o questionário de Antonovsky SOC (SOC-13) e seus filhos tiveram a cavidade bucal examinada para cárie dentária, higiene bucal, defeito de desenvolvimento de esmalte e má oclusão. Esta pesquisa foi aprovada pelo Comitê de Ética em Pesquisa com Seres Humanos da UFMG. As mães de crianças/adolescentes com MPS apresentaram menores valores de SOC [média: 33,3 (+4,0)/mediana: 32,0] quando comparadas com as mães de crianças/adolescentes sem MPS [média: 36,9 (+4,5) /mediana: 37,0] (p<0,001). As mães de crianças/adolescentes com MPS apresentaram menores valores de SOC quando os filhos apresentavam um ou mais dentes cariados [31,5 (+3,2)] quando comparados com aqueles sem dentes cariados [35,7 (+3,8)] (p=0,004). As mães de crianças/adolescentes com MPS apresentaram menores valores de SOC quando os filhos apresentavam um ou mais dentes perdidos [30,2 (+0,9)], quando comparados com aqueles sem nenhum dente perdido [33,8 (+4,1)] (p=0,046). As mães de crianças/adolescentes com MPS apresentaram valores menores de SOC. As mães de filhos com MPS e 10 cárie dentária e/ou dentes perdidos foram identificadas com valores menores de SOC. O estudo do Senso de Coerência Materno e saúde bucal de crianças/adolescentes com MPS permite uma abordagem multidisciplinar mais adequada para as famílias, especialmente as mães, e os profissionais de saúde que os assistem. Dessa forma, é possível promover uma melhor qualidade de vida e saúde bucal para essa parcela da população

Mucopolysaccharidosis (MPS) are a group of inherited diseases caused by enzyme inadequacy of lysosomes, responsible for the degradation of glycosaminoglycans (GAG). Sense of Coherence (SOC) is a theoretical construct used to understand why some people fall ill after the occurance of a stressful situation and some not .This study aimed to assess the association between the presence of MPS in children/adolescents and the mother?s sense of coherence (SOC), as well as the association between mother?s SOC and the oral health status of children/adolescents with and without MPS. A paired cross-sectional study was carried out with a convenience sample of 29 children/adolescents with MPS and 29 children/adolescents without MPS, with age ranging from of 3 to 21 years, and their mothers. They were individually matched by sex and age. Data was collected at a clinic of the School of Dentistry of the Universidade Federal de Minas Gerais, in the city of Belo Horizonte, in the southeast of Brazil. Mothers who agreed to participate completed the Antonovsky?s SOC instrument (SOC-13) and had their child?s oral cavity examined for caries experience, oral hygiene, developmental defects of enamel, and occlusal problems. This study was approved by the Human Research Ethics Committee of the Universidade Federal de Minas Gerais. The children/adolescents with and without MPS and their mothers were selected in a university hospital. Mothers of children with MPS had lower SOC values [mean: 33.3 (+4.0)/median: 32.0] compared with mothers of children without MPS [mean: 36.9 (+4.5) /median: 37.0] (p<0.001). In the group of children/adolescents with MPS, the mother's SOC values were lower for those children with one or more decayed teeth [31.5 (+3.2)] than for those children/adolescents without decayed teeth [35.7 (+3.8)] (p=0.004). Mother´s SOC values in the group with MPS were lower for those children/adolescents with one or more missing teeth [30.2 (+0.9)] than for those children/adolescents identified without missing teeth [33.8 (+4.1)] (p=0.046). Mothers of children with MPS had lower mother's SOC values. Mother´s of children/adolescents with MPS and dental caries and/or missing teeth had SOC lower values. The study of Mother´s SOC 12 and oral health status of children/adolescents with MPS allows an appropriate approach to the families, especially mothers, and the health professionals who assist them, leading to a better quality of life for these population

From bedside to cell biology: a century of history on lysosomal dysfunction.

Lysosomal storage disorders (LSDs) are a group of rare genetic diseases, generally caused by a deficiency of specific lysosomal enzymes, which results in abnormal accumulation of undegraded substrates. The first clinical reports describing what were later shown to be LSDs were published more than a hundred years ago. In general, the history and pathophysiology of LSDs has impacted on our current knowledge of lysosomal biology. Classically, depending on the nature of the substrates, LSDs can be divided into different subgroups. The mucopolysaccharidoses (MPSs) are those caused by impaired degradation of glycosaminoglycans (GAGs). Amongst LSDs, the MPSs are a major group of pathologies with crucial historical relevance, since their study has revealed important biological pathways and highlighted interconnecting pathological cascades which are still being unveiled nowadays. Here we review the major historical discoveries in the field of LSDs and their impact on basic cellular knowledge and practical applications. Attention will be focused on the MPSs, with occasional references to other LSDs. We will show as studies on the metabolic basis of this group of diseases have increased our knowledge of the complex degradative pathways associated with the lysosome and established the basis to the development of specific therapeutic approaches aiming at correcting or, at least ameliorating their associated phenotypes.

The mucopolysaccharidoses (a review).

The mucopolysaccharidoses are a group of genetic diseases characterized by storage of incompletely degraded glycosaminoglycans. Such storage causes marked distortion of many tissues with consequent severe somatic changes and mental retardation. Storage of glycosaminoglycans results from markedly diminished activity of specific hydrolases requisite for the normal degradation of glycosaminoglycans. The specific enzymic defects have been identified in nine different diseases. In some cases evidence has been obtained indicating the existence of additional allelic diseases based on the same enzyme. The knowledge obtained from these studies has made prenatal diagnosis possible and has led to the possibility that therapy may be undertaken utilizing enzyme replacement.