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Objective: Mucopolysaccharidosis is a rare genetic disease characterized by the intralysosomal deposition of glycosaminoglycans. Cardiovascular impairment is a common feature. Cardiac signs and symptoms are underestimated due to the disease involvement in other organs. Enzyme replacement therapy can be used in mucopolysaccharidosis I, II, IV, and VI. Thus, the knowledge about the use of new echocardiography tools is relevant to improve the care of this population. This study aimed to describe left ventricular function assessment by conventional echocardiography and left ventricular global longitudinal strain analysis and compare the alterations in patients receiving enzyme replacement therapy and who had different ages at the start of therapy. Method: Outpatient‐based descriptive study. The patients were submitted to conventional echocardiography and left ventricular global longitudinal strain measurement. Results: Sixteen patients were evaluated; median age of 14.2 years (SD = 5.2 years). Left ventricular hypertrophy was found in nine patients (56.2%). All patients had preserved left ventricular systolic function (Simpson and Teichholz). Nine (56.2%) patients showed alterations in left ventricular global longitudinal strain. The study showed a positive association between left ventricular hypertrophy and alteration in the left ventricular global longitudinal strain, and late start of enzyme replacement therapy and alteration in the left ventricular global longitudinal strain. Conclusion: Echocardiographic alterations in patients with mucopolysaccharidosis were frequently observed, especially alterations in the left ventricular geometry and subclinical dysfunction. Patients who had a late enzyme replacement therapy start showed an association with worse left ventricular global longitudinal strain values, reinforcing the need for early diagnosis and treatment. The use of new echocardiographic tools may improve the follow‐up of these patients. Resumo: Objetivo: A mucopolissacaridose é uma doença genética rara, caracterizada por depósito intralisossômico de glicosaminoglicanos. O comprometimento cardiovascular é frequente. Sinais e sintomas cardíacos são subestimados pelo envolvimento da doença em outros órgãos. A terapia de reposição enzimática pode ser usada em mucopolissacaridose I, II, IV e VI. Assim, o conhecimento da aplicação de novas ferramentas de ecocardiografia é relevante para melhorar a assistência dessa população. Este estudo visou descrever a função do ventrículo esquerdo pelo ecocardiograma convencional e pela análise do strain global longitudinal do ventrículo esquerdo e comparar as alterações em pacientes que fazem uso da terapia de reposição enzimática e que tiveram idades distintas de início da terapia. Método: Estudo descritivo de base ambulatorial. Os pacientes foram submetidos à ecocardiografia convencional e medida do strain global longitudinal do ventrículo esquerdo. Resultados: Foram avaliados 16 pacientes; mediana de 14,2 anos (desvio: 5,2 anos). Hipertrofia do ventrículo esquerdo foi encontrada em nove pacientes (56,2%). Todos os pacientes tiveram função sistólica do ventrículo esquerdo preservada (Simpson e Teichholz). Nove (56,2%) pacientes apresentaram alteração no strain global longitudinal do ventrículo esquerdo. O estudo mostrou associação positiva entre hipertrofia do ventrículo esquerdo e alteração no strain global longitudinal do ventrículo esquerdo e início tardio da terapia de reposição enzimática e alteração no strain global longitudinal do ventrículo esquerdo. Conclusão: Alterações ecocardiográficas em pacientes com mucopolissacaridose foram frequentes, especialmente alterações na geometria e disfunção subclínica do ventrículo esquerdo. Pacientes que iniciaram tardiamente a terapia de reposição enzimática apresentaram associação com piores valores de strain global longitudinal do ventrículo esquerdo, o que reforça a necessidade do diagnóstico e tratamento precoces. O uso de novas ferramentas de ecocardiografia pode melhorar o acompanhamento desses pacientes. Keywords: Mucopolysaccharidosis, Echocardiography, Cardiac function tests, Enzyme replacement therapy, Palavras‐chave: Mucopolissacaridose, Ecocardiografia, Testes de função cardíaca, Terapia de reposição enzimática

The Brazilian Policy of Comprehensive Care for People with Rare Diseases (BPCCPRD) was established by the Ministry of Health to reduce morbidity and mortality and improve the quality of life of people with rare diseases (RD). Several laboratory tests, most using molecular genetic technologies, have been incorporated by the Brazilian Public Health System, and 18 specialised centres have so far been established at university hospitals (UH) in the capitals of the Southern, Southeastern and Northeastern regions. However, whether the available human and technological resources in these services are appropriate and sufficient to achieve the goals of care established by the BPCCPRD is unknown. Despite great advances in diagnosis, especially due to new technologies and the recent structuring of clinical assessment of RD in Brazil, epidemiological data are lacking and when available, restricted to specific disorders. This position paper summarises the performance of a nationally representative survey on epidemiology, clinical status, and diagnostic and therapeutic resources employed for individuals with genetic and non-genetic RD in Brazil. The Brazilian Rare Disease Network (BRDN) is under development, comprising 40 institutions, including 18 UH, 17 Rare Diseases Reference Services and five Newborn Screening Reference Services. A retrospective study will be initially conducted, followed by a prospective study. The data collection instrument will use a standard protocol with sociodemographic data and clinical and diagnostic aspects according to international ontology. This great collaborative network is the first initiative of a large epidemiological data collection of RD in Latin America, and the results will increase the knowledge of RD in Brazil and help health managers to improve national public policy on RD in Brazil.

Identifying the genetic etiology in a person with hearing loss (HL) is challenging due to the extreme genetic heterogeneity in HL and the population-specific variability. In this study, after excluding GJB2 variants, targeted resequencing of 180 deafness-related genes revealed the causative variants in 11 of 19 (58%) Brazilian probands with autosomal recessive HL. Identified pathogenic variants were in MYO15A (10 families) and CLDN14 (one family). Remarkably, the MYO15A p.(Val1400Met) variant was identified in eight families from the city of Monte Santo in the northeast region of Brazil. Haplotype analysis of this variant was consistent with a single founder. No other cases with this variant were detected among 105 simplex cases from other cities of northeastern Brazil, suggesting that this variant is confined to a geographical region. This study suggests that it is feasible to develop population-specific screening for deafness variants once causative variants are identified in different geographical groups.

OBJETIVOS: descrever e avaliar o perfil do Programa de Triagem Neonatal baiano em 2003. MÉTODOS: estudo descritivo baseado no banco de dados do Serviço de Referência de Triagem Neonatal baiano com todos os recém-nascidos que realizaram a triagem na rede de coleta do Estado em 2003. RESULTADOS: observou-se implantação do programa em 94,5% dos municípios. A média mensal de testados foi de 13.991 (72,51% dos recém-nascidos registrados). Na coleta, 63,9% das crianças estavam com idade entre oito dias e um mês, 14,5% com até sete dias e 21,6% com mais de um mês. A incidência observada foi de 1:22.000 para fenilcetonúria, 1:4.000 para o hipotireoidismo congênito e 1:650 para as hemoglobinopatias. CONCLUSÕES: o Programa de Triagem Neonatal baiano mostrou, em 2003, dificuldades quanto a cobertura preconizada em 100%; a faixa etária ideal para realização da coleta; ao tempo entre a coleta e a chegada das amostras ao Serviço de Referência em Triagem Neonatal; ao tempo de entrega dos resultados à família; e ao tempo de reconvocação dos casos positivos. Assim, são necessárias algumas melhorias para agilizar esses processos.OBJECTIVES: describe and assess the Neonatal Screening Program of Bahia in 2003. METHODS: descriptive study based on the databank of the Neonatal Screening Reference Service of Bahia in all newborns previously screened in the data collecting network of 2003. RESULTS: the program was implemented in 94.5% of the municipalities. The monthly average of newborns assessed was of 13.991 (72.51% of the registered newborns). During data collection, 63.9% of the children were between eight days and one month old, 14.5% seven days old and 21.6% over one month old. The incidence determined was 1:22,000 for phenylketonuria, 1:4,000 for congenital hypothyroidism and 1:650 for sickle cell disease. CONCULSIONS: the Neonatal Screening Program of Bahia in 2003 fell short to the expected coverage of 100%, failed in selecting the ideal age group for blood sampling; there were difficulties as well related to the time elapsed between blood collection and samples arrival to the Neonatal Screening Reference Service; of test delivery to the family; and of positive cases recall. Therefore, improvements are needed to expedite procedures.

Mutations in the gene encoding phenylalanine hydroxylase (PAH, EC 1.14.16.1) are associated with various degrees of hyperphenylalaninemia, including classical phenylketonuria (PKU). We examined the PAH gene in a Brazilian PKU family of African origin and identified three missense variants, R252W (c.754C → T), K274E (c.820A → G), and I318T (c.953T → C), the two latter of which were transmitted in cis. Expression analyses in two different in vitro systems showed that I318T is associated with profoundly decreased enzyme activity, whereas the enzyme activity of K274E is indistinguishable from that of the wild-type protein. Detailed kinetic analyses of PAH expressed in E. coli showed that the K274E mutant protein has kinetic properties similar to that of the wild-type protein. Population studies have suggested that the K274E variant occurs on approximately 4% of African-American PAH alleles, whereas the neonatal screening incidence of PKU among African Americans is only 1:100,000. This is to our knowledge the first demonstration of a PAH missense variant with no apparent association to PAH deficiency. Awareness of this common variant may be helpful to laboratories that perform molecular diagnosis of PAH deficiency in populations of African origin.