Abstract Mucopolysaccharidosis type IIIB (MPS IIIB) is caused by deficiency of alpha-N-acetylglucosaminidase, leading to storage of heparan sulphate. The disease is characterized by intellectual disability and hyperactivity, among other neurological and somatic features. Here we studied retrospective data from a total of 19 MPS IIIB patients from Brazil, aiming to evaluate disease progression. Mean age at diagnosis was 7.2 years. Speech delay was one of the first symptoms to be identified, around 2-3 years of age. Behavioral alterations include hyperactivity and aggressiveness, starting around age four. By the end of the first decade, patients lost acquired abilities such as speech and ability to walk. Furthermore, as disease progresses, respiratory, cardiovascular and joint abnormalities were found in more than 50% of the patients, along with organomegaly. Most common cause of death was respiratory problems. The disease progression was characterized in multiple systems, and hopefully these data will help the design of appropriate clinical trials and clinical management guidelines. alphaNacetylglucosaminidase, alphaNacetylglucosaminidase alpha N acetylglucosaminidase, acetylglucosaminidase alpha-N-acetylglucosaminidase sulphate features 1 Brazil 72 7 2 7. identified 23 3 2- aggressiveness four decade walk Furthermore progresses 50 organomegaly problems systems guidelines 5

Abstract Lysosomal diseases (LDs), also known as lysosomal storage diseases (LSDs), are a heterogeneous group of conditions caused by defects in lysosomal function. LDs may result from deficiency of lysosomal hydrolases, membrane-associated transporters or other non-enzymatic proteins. Interest in the LD field is growing each year, as more conditions are, or will soon be treatable. In this article, we review the diagnosis of LDs, from clinical suspicion and screening tests to the identification of enzyme or protein deficiencies and molecular genetic diagnosis. We also cover the treatment approaches that are currently available or in development, including hematopoietic stem cell transplantation, enzyme replacement therapy, small molecules, and gene therapy.

Abstract Lysosomal storage diseases (LSDs) are inherited conditions caused by impaired lysosomal function and consequent substrate storage, leading to a range of clinical manifestations, including cardiovascular disease. This may lead to significant symptoms and even cardiac failure, which is an important cause of death among patients. Currently available treatments do not completely correct cardiac involvement in the LSDs. Gene therapy has been tested as a therapeutic alternative with promising results for the heart disease. In this review, we present the results of different approaches of gene therapy for LSDs, mainly in animal models, and its effects in the heart, focusing on protocols with cardiac functional analysis.

Abstract Lysosomal storage disorders (LSDs) are a group of diseases with multisystemic features. Current treatments have limitations and gene therapy arises as a promising treatment option. Here, we discuss some of the most recent studies for gene therapy in LSD, vectors used, and outcomes. In particular, the approaches used in animal models aiming to correct the central nervous system, the eye, and the bones are highlighted. Finally, we discuss the recent reports of clinical trials using this technology for these diseases. We conclude that gene therapy for LSD has gathered a substantial amount of evidence from animal models to know its potential and limitations. First evidences from clinical trials using both adeno-associated and lentiviral vectors show that this approach is safe and efficient and therefore could provide an effective treatment for several LSD in the near future.

Abstract Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is a lysosomal storage disorder caused by a deficient N-acetylgalactosamine-6-sulfate sulfatase activity, leading to cellular storage of undegraded keratan sulfate. Recently enzyme replacement therapy (ERT) was approved for MPS IVA, but some of ERT effects are still unknown. In the present study, we aimed to evaluate the efficacy of elosulfase alfa upon glycosaminoglycan (GAG) storage in peripheral blood white blood cells of patients with MPS IVA treated for 6 months, comparing samples from patients who received weekly infusions of enzyme (ERT-W) versus infusions every other week (ERT-EOW) versus placebo. A significant reduction in GAG storage was observed in both ERT-treated groups, with weekly ERT showing slightly better performance than ERT-EOW.

Neste trabalho estimamos o custo do tratamento hospitalar do pé diabético e discutimos a literatura referente à profilaxia destas lesões. Para isto revisamos os prontuários dos pacien tes submetidos a tratamento cirúrgico num período de 16 meses em um hospital público e revisamos os métodos de prevenção do pé diabético. Foram 44 internações com duração média de 11,93 dias (± 6,34), 61 procedimentos cirúrgicos, com amputações em 65% dos casos. Encontramos um custo médio de R$ 4.367,05 (± 9.249,01) e um custo total de R$ 192.150,40 para estes tratamentos hospitalares. O tratamento do pé diabético teve um alto custo e exigiu amputações na maioria dos casos. A revisão da literatura evidenciou diversos modelos possíveis de serem adotados para atuar na profilaxia de lesões associadas ao pé diabético, os quais podem evitar amputações e economizar recursos.

In this work the cost of hospital treatment for diabetic foot wounds was estimated and the literature regarding prophylaxis for these lesions was examined. For this purpose, the records of all patients with diabetic foot symptoms submitted to surgical treatment over a period of 16 months in a public hospital were reviewed. There were 44 admissions with an average hospitalization period of 11.93 days, (± 6.34), 61 surgical procedures, with amputations in 65% of the cases. An average cost of R$ 4,367.05 (± 9249.01) and a total cost of R$ 192,150.40 was calculated for the hospital treatment involved. Treatment of diabetic foot symptoms had a high cost and required amputation in the majority of cases. A review of the literature revealed many possible models to be adopted for action in the prophylaxis of wounds associated with the diabetic foot, which can avoid amputations and save funds.

Neste trabalho estimamos o custo do tratamento hospitalar do pé diabético e discutimos a literatura referente à profilaxia destas lesões. Para isto revisamos os prontuários dos pacien tes submetidos a tratamento cirúrgico num período de 16 meses em um hospital público e revisamos os métodos de prevenção do pé diabético. Foram 44 internações com duração média de 11,93 dias (± 6,34), 61 procedimentos cirúrgicos, com amputações em 65% dos casos. Encontramos um custo médio de R$ 4.367,05 (± 9.249,01) e um custo total de R$ 192.150,40 para estes tratamentos hospitalares. O tratamento do pé diabético teve um alto custo e exigiu amputações na maioria dos casos. A revisão da literatura evidenciou diversos modelos possíveis de serem adotados para atuar na profilaxia de lesões associadas ao pé diabético, os quais podem evitar amputações e economizar recursos.

In this work the cost of hospital treatment for diabetic foot wounds was estimated and the literature regarding prophylaxis for these lesions was examined. For this purpose, the records of all patients with diabetic foot symptoms submitted to surgical treatment over a period of 16 months in a public hospital were reviewed. There were 44 admissions with an average hospitalization period of 11.93 days, (± 6.34), 61 surgical procedures, with amputations in 65% of the cases. An average cost of R$ 4,367.05 (± 9249.01) and a total cost of R$ 192,150.40 was calculated for the hospital treatment involved. Treatment of diabetic foot symptoms had a high cost and required amputation in the majority of cases. A review of the literature revealed many possible models to be adopted for action in the prophylaxis of wounds associated with the diabetic foot, which can avoid amputations and save funds.

The Latin American School of Human and Medical Genetics (ELAG) is the main course of its kind in the genetics field in Latin America. Here we describe the main challenges regarding the organization of such event, including how we obtain funding and how we proceed with student selection. Thus, we aim to share our experience with other groups that intend to follow this format to create similar events in other areas in this region of the world.

An alternative approach to somatic gene therapy is to deliver the therapeutic protein by implanting genetically modified cells that could overexpress the gene of interest. Microencapsulation devices were designed to protect cells from host rejection and prevent the foreign cells from spreading while allowing protein secretion. Alginate microcapsules form a semi-permeable structure that is suitable for in vivo injection. In this study, we report an effective laboratory protocol for producing calcium alginate microcapsules, following optimization of uniformly shaped and sized particles containing viable cells. Encapsulation of baby hamster kidney (BHK) cells in alginate microcapsules was performed using a simple device consisting of a cylinder of compressed air and a peristaltic pump. A cell suspension flow of 100 mL h-1 and an air jet flow of 10 L min-1 produced the best uniformity of microcapsule size and shape. Cells maintained viability in culture for 4 weeks without any signs of necrosis, and protein diffusion was observed during this period. Our results clearly demonstrated that microisolation of BHK cells in alginate using a simple assembly device could provide an environment that is capable of preserving live cells. In addition, encapsulated cells under the conditions described were able to secrete an active enzyme even after four weeks, thus becoming potentially compatible with therapeutic protein delivery.

Serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1 (SERPINA1) deficiency is one of the main genetic causes related to liver disease in children. In SERPINA1 deficiency the most frequent SERPINA1 alleles found are the PI*S and PI*Z alleles. We used the polymerase chain reaction and the amplification created restriction site (ACRS) technique to investigate the prevalence of the PI*S and PI*Z alleles in a group of Brazilian children (n = 200) with liver disease and established the general frequency of the PI*S allele in our population. We found a significant association of the PI*Z allele and liver disease, but no such relationship was found for the PI*S allele. Our results show that SERPINA1 deficiency due to the PI*Z allele, even when heterozygous, is a frequent cause of liver disease in our group of Brazilian children but that the PI*S allele does not confer an increased risk of hepatic disorders in our group of Brazilian children.