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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

https://doi.org/10.1590/1678-4685-gmb-2023-0285

A needle in a haystack? The impact of a targeted epilepsy gene panel in the identification of a treatable but rapidly progressive metabolic epilepsy: CLN2 disease haystack CLN
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Lourenço, Charles Marques

; Sallum, Juliana Maria Ferraz

; Pereira, Alessandra Marques

; Girotto, Paula Natale

; Kok, Fernando

; Vilela, Daniel Reda Fenga

; Barron, Erika

; Pessoa, André

; de Oliveira, Bibiana Mello

Arquivos de Neuro-Psiquiatria

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2024, Volume 82 N. 5 elocation s00441786854

Abstract: Pt En | Text: Pt En | PDF: Pt | PDF: En

Resumo Antecedentes As lipofuscinoses ceroides neuronais (neuronal ceroid lipofuscinoses, NCLs, em inglês) são um grupo de doenças autossômicas recessivas, hereditárias, lisossomais e neurodegenerativas que causam demência progressiva, crises epiléticas, distúrbios de movimento, atraso/regressão da linguagem, deficiência visual progressiva e morte precoce. A lipofuscinose ceroide neuronal tipo 2 (neuronal ceroid lipofuscinosis type 2, CLN2, em inglês), causada por variantes patogênicas bialélicas do gene TPP1, é a única com terapia-alvo aprovada. O diagnóstico laboratorial é realizado por testes específicos, o que leva a atrasos diagnósticos e, consequentemente, prejudica a disponibilização de tratamento. A epilepsia é uma característica comum e clinicamente identificável entre as NCLs, e o início das convulsões é o principal motivo para as famílias buscarem atendimento médico. Objetivo Avaliar os resultados do Programa de Epilepsia e Genética da América Latina, um painel genético, como uma ferramenta abrangente para a investigação de CLN2 entre outras causas genéticas de epilepsia. Métodos Um total de 1.284 pacientes com epilepsia sem uma causa específica e que tinham pelo menos 1 sintoma associado à CLN2 foram rastreados em busca de variantes em 160 genes associados à epilepsia ou a distúrbios metabólicos que apresentam epilepsia, por meio de um painel genético. Resultados Variantes do gene TPP1 foram identificadas em 25 indivíduos (1,9%), sendo que ; 21 apresentavam duas variantes. As duas variantes mais frequentes foram p.Arg208* e p.Asp276Val, e duas variantes novas foram detectadas neste: p.Leu308Pro e c.89 + 3G > C Intron 2. Conclusão Os resultados sugerem que os painéis genéticos de epilepsia podem ser uma ferramenta útil para confirmar ou excluir o diagnóstico de CLN2 e, se confirmado, fornecer tratamento específico para os pacientes. NCLs inglês recessivas hereditárias epiléticas movimento atrasoregressão atraso regressão linguagem precoce CLN inglês, , TPP terapiaalvo terapia alvo aprovada específicos consequentemente médico Latina genético 1284 284 1.28 16 1,9%, 19 1,9% 9 (1,9%) pArg208 pArg p Arg208 Arg p.Arg208 pAsp276Val pAspVal Asp276Val Asp Val p.Asp276Val neste pLeu308Pro pLeuPro Leu308Pro Leu Pro c89 c 89 c.8 G confirmado 128 28 1.2 1,9 (1,9% pArg20 Arg20 p.Arg20 pAsp AspVal pLeu LeuPro c8 8 c. 12 1. 1, (1,9 pArg2 Arg2 p.Arg2 (1, p.Arg (1 (

Abstract Background Neuronal ceroid lipofuscinoses (NCL) are a group of autosomal recessive, inherited, lysosomal, and neurodegenerative diseases that causes progressive dementia, seizures, movement disorders, language delay/regression, progressive visual failure, and early death. Neuronal ceroid lipofuscinosis type 2 (CLN2), caused by biallelic pathogenic variants of the TPP1 gene, is the only NCL with an approved targeted therapy. The laboratory diagnosis of CLN2 is established through highly specific tests, leading to diagnostic delays and eventually hampering the provision of specific treatment for patients with CLN2. Epilepsy is a common and clinically-identifiable feature among NCLs, and seizure onset is the main driver for families to seek medical care. Objective To evaluate the results of the Latin America Epilepsy and Genetics Program, an epilepsy gene panel, as a comprehensive tool for the investigation of CLN2 among other genetic causes of epilepsy. Methods A total of 1,284 patients with epilepsy without a specific cause who had at least 1 symptom associated with CLN2 were screened for variants in 160 genes associated with epilepsy or metabolic disorders presenting with epilepsy through an epilepsy gene panel. Results Variants of the TPP1 gene were identified in 25 individuals (1.9%), 21 of them with 2 variants. The 2 most frequently reported variants were p.Arg208* and p.Asp276Val, and 2 novel variants were detected in the present study: p.Leu308Pro and c.89 + 3G > C Intron 2. Conclusion The results suggest that these genetic panels can be very useful tools to confirm or exclude CLN2 diagnosis and, if confirmed, provide disease-specific treatment for the patients. (NCL recessive inherited lysosomal dementia seizures delayregression delay regression delay/regression failure death CLN2, CLN , (CLN2) TPP therapy tests clinicallyidentifiable clinically identifiable NCLs care Program panel 1284 284 1,28 16 1.9%, 19 1.9% 9 (1.9%) pArg208 pArg p Arg208 Arg p.Arg208 pAsp276Val pAspVal Asp276Val Asp Val p.Asp276Val study pLeu308Pro pLeuPro Leu308Pro Leu Pro c89 c 89 c.8 G confirmed diseasespecific disease (CLN2 128 28 1,2 1.9 (1.9% pArg20 Arg20 p.Arg20 pAsp AspVal pLeu LeuPro c8 8 c. (CLN 12 1, 1. (1.9 pArg2 Arg2 p.Arg2 (1. p.Arg (1 (

https://doi.org/10.1055/s-0044-1786854

Posicionamento Brasileiro sobre Síndrome da Quilomicronemia Familiar – 2023 202 20 2
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Izar, Maria Cristina de Oliveira

; Santos Filho, Raul Dias dos

; Assad, Marcelo Heitor Vieira

; Chagas, Antonio Carlos Palandri

; Toledo Júnior, Alceu de Oliveira

; Nogueira, Ana Cláudia Cavalcante

; Souto, Ana Cristina Carneiro Fernandes

; Lottenberg, Ana Maria

; Chacra, Ana Paula Marte

; Ferreira, Carlos Eduardo dos Santos

; Lourenço, Charles Marques

; Valerio, Cynthia Melissa

; Cintra, Dennys Esper

; Fonseca, Francisco Antonio Helfenstein

; Campana, Gustavo Aguiar

; Bianco, Henrique Tria

; Lima, Josivan Gomes de

; Castelo, Maria Helane Costa Gurgel

; Scartezini, Marileia

; Moretti, Miguel Antonio

; Barreto, Natasha Slhessarenko Fraife

; Maia, Rayana Elias

; Montenegro Junior, Renan Magalhães

; Alves, Renato Jorge

; Figueiredo, Roberta Marcondes Machado

; Fock, Rodrigo Ambrosio

; Martinez, Tânia Leme da Rocha

; Giraldez, Viviane Zorzanelli Rocha

Arquivos Brasileiros de Cardiologia

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2023, Volume 120 N. 4 elocation e20230203

Abstract: Pt | Text: Pt | PDF: Pt

https://doi.org/10.36660/abc.20230203

Metachromatic leukodystrophy: pediatric presentation and the challenges of early diagnosis
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Borges, Frederico Mendes

; Costa, Maria Júlia Gonzalez da

; Carneiro, Zumira Aparecida

; Lourenço, Charles Marques

Revista da Associação Médica Brasileira

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oct 2020, Volume 66 N. 10 Pages 1344 - 1350

Abstract: En | Text: En | PDF: En

https://doi.org/10.1590/1806-9282.66.10.1344 1036 downloads

Development of a Clinical Algorithm for the Early Diagnosis of Mucopolysaccharidosis III
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Escolar, Maria

; Bradshaw, Jessica

; Byers, Valerie Tharp

; Giugliani, Roberto

; Golightly, Lynn

; Lourenço, Charles Marques

; McDonald, Kimberly

; Muschol, Nicole

; Newsom-Davis, Imogen

; O’Neill, Cara

; Peay, Holly L.

; Siedman, Jennifer

; Solano, Martha L.

; Wirt, Tessa

; Wood, Tim

; Zwaigenbaum, Lonnie

Journal of Inborn Errors of Metabolism and Screening

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2020, Volume 8 elocation e20200002

Abstract: En | Text: En | PDF: En

Abstract Mucopolysaccharidosis III (MPS III) is a rare inherited metabolic disease primarily affecting the central nervous system, leading to developmental and/or speech regression. Early diagnosis of the disease is important to introduce appropriate management measures and to optimize therapeutic outcomes. The diagnosis of MPS III is often significantly delayed due to the rarity of the disease, the more attenuated somatic presentation compared to other MPS types, and the symptom overlap with other developmental disorders. To shorten the time to diagnosis, a list of eight early signs and symptoms was identified through an expert system approach by a global, multidisciplinary working group of 13 specialists with expertise in various aspects of MPS and developmental disorders and three parents of MPS III patients. Coarse facial features and persistent hirsutism or prominent, thick eyebrows were identified as the most important MPS III early signs. The list of eight early MPS III signs and symptoms is the first step towards the development of a clinical algorithm aiming to identify neonates and infants with MPS III before the onset of neurocognitive damage, ultimately shortening the diagnostic journey of MPS III patients.

https://doi.org/10.1590/2326-4594-jiems-2020-0002 1396 downloads

Niemann-Pick disease type C: a case series of Brazilian patients
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Lorenzoni, Paulo José

; Cardoso, Elaine

; Crippa, Ana C. S.

; Lourenço, Charles Marques

; Souza, Fernanda Timm Seabra

; Giugliani, Roberto

; Saraiva-Pereira, Maria Luiza

; Raskin, Salmo

; Bruck, Isac

; Kay, Cláudia S. K.

; Scola, Rosana H.

; C.Werneck, Lineu

; Teive, Hélio A. G.

Arquivos de Neuro-Psiquiatria

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mar 2014, Volume 72 N. 3 Pages 214 - 218

Abstract: Pt En | Text: Pt En | PDF: Pt | PDF: En

O objetivo desse estudo foi analisar uma série de casos de pacientes brasileiros com doença de Niemann-Pick tipo C (NP-C). Método Correlação entre manifestações clínicas, alterações laboratoriais, estudo molecular e resposta ao tratamento foram realizadas. Resultado A amostra consiste de 5 pacientes com idade entre 8 e 26 anos. Paralisia do olhar vertical supranuclear, ataxia cerebelar, demência, distonia e disartria estavam presentes em todos os casos. Coloração de filipina na cultura de fibroblastos mostrou padrão “clássico” em dois pacientes e padrão “variante” em três casos. O estudo molecular encontrou mutações no gene NPC1 em todos os alelos. O tratamento com miglustate foi realizado em 4 pacientes. Conclusão Embora coloração de filipina seja utilizada para confirmar o diagnóstico, o histiócito azul-marinho no aspirado de medula óssea frequentemente auxilia a confirmar o diagnóstico de NP-C. A mutação p.P1007A está correlacionada com o padrão “ variante” na coloração de filipina. A resposta ao tratamento com miglustate parece estar correlacionada com a idade e escore de desabilidade no momento do diagnóstico.

The aim of the study was to analyze a series of Brazilian patients with Niemann-Pick disease type C (NP-C). Method Correlations between clinical findings, laboratory data, molecular findings and treatment response are presented. Result The sample consisted of 5 patients aged 8 to 26 years. Vertical supranuclear gaze palsy, cerebellar ataxia, dementia, dystonia and dysarthria were present in all cases. Filipin staining showed the “classical” pattern in two patients and a “variant” pattern in three patients. Molecular analysis found mutations in the NPC1 gene in all alleles. Miglustat treatment was administered to 4 patients. Conclusion Although filipin staining should be used to confirm the diagnosis, bone marrow sea-blue histiocytes often help to diagnosis of NP-C. The p.P1007A mutation seems to be correlated with the “variant” pattern in filipin staining. Miglustat treatment response seems to be correlated with the age at disease onset and disability scale score at diagnosis.

https://doi.org/10.1590/0004-282X20130249 7066 downloads

Enzyme replacement therapy for Mucopolysaccharidosis Type I among patients followed within the MPS Brazil Network
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Dornelles, Alícia Dorneles

; Pinto, Louise Lapagesse de Camargo

; Paula, Ana Carolina de

; Steiner, Carlos Eduardo

; Lourenço, Charles Marques

; Kim, Chong Ae

; Horovitz, Dafne Dain Gandelman

; Ribeiro, Erlane Marques

; Valadares, Eugênia Ribeiro

; Goulart, Isabela

; Souza, Isabel C. Neves de

; Neri, João Ivanildo da Costa

; Santana-da-Silva, Luiz Carlos

; Silva, Luiz Roberto

; Ribeiro, Márcia

; Oliveira Sobrinho, Ruy Pires de

; Giuglianiand, Roberto

; Schwartz, Ida Vanessa Doederlein

Genetics and Molecular Biology

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2014, Volume 37 N. 1 Pages 23 - 29

Abstract: En | Text: En | PDF: En

Mucopolysaccharidosis type I (MPS I) is a rare lysosomal disorder caused by deficiency of alph-L-iduronidase. Few clinical trials have assessed the effect of enzyme replacement therapy (ERT) for this condition. We conducted an exploratory, open-label, non-randomized, multicenter cohort study of patients with MPS I. Data were collected from questionnaires completed by attending physicians at the time of diagnosis (T1; n = 34) and at a median time of 2.5 years later (T2; n = 24/34). The 24 patients for whom data were available at T2 were allocated into groups: A, no ERT (9 patients; median age at T1 = 36 months; 6 with severe phenotype); B, on ERT (15 patients; median age at T1 = 33 months; 4 with severe phenotype). For all variables in which there was no between-group difference at baseline, a delta of ;±20% was considered clinically relevant. The following clinically relevant differences were identified in group B in T2: lower rates of mortality and reported hospitalization for respiratory infection; lower frequency of hepatosplenomegaly; increased reported rates of obstructive sleep apnea syndrome and hearing loss; and stabilization of gibbus deformity. These changes could be due to the effect of ERT or of other therapies which have also been found more frequently in group B. Our findings suggest MPS I patients on ERT also receive a better overall care. ERT may have a positive effect on respiratory morbidity and overall mortality in patients with MPS I. Additional studies focusing on these outcomes and on other therapies should be performed.

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Proptosis in a family with the p16 Leuc-to-Prol mutation in the PMP22 gene (CMT 1E)
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Calia, Leandro

; Marques Jr., Wilson

; Gouvea, Silmara P.

; Lourenço, Charles Marques

; Oliveira, Acary S. B. de

Arquivos de Neuro-Psiquiatria

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may 2013, Volume 71 N. 5 Pages 332 - 333

Abstract: En | Text: En | PDF: En

https://doi.org/10.1590/0004-282X20130031 1613 downloads

X-linked adrenoleukodystrophy in heterozygous female patients: women are not just carriers
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Lourenço, Charles Marques

; Simão, Gustavo Novelino

; Santos, Antonio Carlos

; Marques Jr, Wilson

Arquivos de Neuro-Psiquiatria

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jul 2012, Volume 70 N. 7 Pages 487 - 491

Abstract: Pt En | Text: Pt En | PDF: Pt | PDF: En

A adrenoleucodistrofia ligada ao X (ADL-X) é uma doença recessiva ligada ao X, associada à grande variabilidade clínica. Mulheres heterozigotas portadoras do gene causador da doença são consideradas, tradicionalmente, como clinicamente normais ou com fenótipo clínico muito discreto. No entanto, a apresentação clínica deste grupo necessita ser melhor caracterizada e sistematizada. OBJETIVOS: Revisar e sistematizar as principais características clínicas de mulheres heterozigotas para ADL-X, seguidas em serviço de neurogenética. MÉTODOS: Foram revisados os principais achados clínicos, bioquímicos e neurorradiológicos das mulheres seguidas no serviço com o diagnóstico bioquímico de ADL-X. RESULTADOS: Nove mulheres foram identificadas e classificadas em três grupos: com doença grave e incapacitante; com evolução mais insidiosa e sintomas de paraparesia espástica; e com sintomas discretos apresentando diminuição da sensibilidade vibratória, reflexos vivos, mas sem queixas clínicas. A maioria dessas mulheres não possuía história familiar positiva para ALD-X. CONCLUSÕES: Mulheres heterozigotas para ALD-X apresentam um amplo espectro de manifestações clínicas, variando desde um fenótipo leve, subclínico até apresentações graves e incapacitantes.

X-linked adrenoleukodystrophy (X-ALD) is a recessive X-linked disorder associated with marked phenotypic variability. Female carriers are commonly thought to be normal or only mildly affected, but their disease still needs to be better described and systematized. OBJECTIVES: To review and systematize the clinical features of heterozygous women followed in a Neurogenetics Clinic. METHODS: We reviewed the clinical, biochemical, and neuroradiological data of all women known to have X-ADL. RESULTS: The nine women identified were classified into three groups: with severe and aggressive diseases; with slowly progressive, spastic paraplegia; and with mildly decreased vibratory sensation, brisk reflexes, and no complaints. Many of these women did not have a known family history of X-ALD. CONCLUSIONS: Heterozygous women with X-ADL have a wide spectrum of clinical manifestations, ranging from mild to severe phenotypes.

14191 downloads Cited 1 time in SciELO

10.

Mucopolysaccharidosis I, II, and VI: brief review and guidelines for treatment
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Giugliani, Roberto

; Federhen, Andressa

; Muñoz Rojas, Maria Verônica

; Vieira, Taiane

; Artigalás, Osvaldo

; Lapagesse Pinto, Louise

; Azevedo, Ana Cecília

; Acosta, Angelina

; Bonfim, Carmen

; Lourenço, Charles Marques

; Chong Ae, Kim

; Horovitz, Dafne

; Bonfim, Denize

; Norato, Denise

; Marinho, Diane

; Palhares, Durval

; Santos, Emerson Santana

; Ribeiro, Erlane

; Valadares, Eugênia

; Guarany, Fábio

; Lucca, Gisele Rosone de

; Pimentel, Helena

; Souza, Isabel Neves de

; Correa Neto, Jordão

; Fraga, José Carlos

; Goes, José Eduardo

; Cabral, José Maria

; Simionato, José

; Llerena Jr., Juan

; Jardim, Laura

; Giuliani, Liane

; Silva, Luiz Carlos Santana da

; Santos, Mara L.

; Moreira, Maria Angela

; Kerstenetzky, Marcelo

; Ribeiro, Márcia

; Ruas, Nicole

; Barrios, Patricia

; Aranda, Paulo

; Honjo, Rachel

; Boy, Raquel

; Costa, Ronaldo

; Souza, Carolina

; Alcantara, Flavio F.

; Avilla, Silvio Gilberto A.

; Fagondes, Simone

; Martins, Ana Maria

Genetics and Molecular Biology

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2010, Volume 33 N. 4 Pages 589 - 604

Abstract: En | Text: En | PDF: En

Mucopolysaccharidoses (MPS) are rare genetic diseases caused by the deficiency of one of the lysosomal enzymes involved in the glycosaminoglycan (GAG) breakdown pathway. This metabolic block leads to the accumulation of GAG in various organs and tissues of the affected patients, resulting in a multisystemic clinical picture, sometimes including cognitive impairment. Until the beginning of the XXI century, treatment was mainly supportive. Bone marrow transplantation improved the natural course of the disease in some types of MPS, but the morbidity and mortality restricted its use to selected cases. The identification of the genes involved, the new molecular biology tools and the availability of animal models made it possible to develop specific enzyme replacement therapies (ERT) for these diseases. At present, a great number of Brazilian medical centers from all regions of the country have experience with ERT for MPS I, II, and VI, acquired not only through patient treatment but also in clinical trials. Taking the three types of MPS together, over 200 patients have been treated with ERT in our country. This document summarizes the experience of the professionals involved, along with the data available in the international literature, bringing together and harmonizing the information available on the management of these severe and progressive diseases, thus disclosing new prospects for Brazilian patients affected by these conditions.

8605 downloads Cited 6 times in SciELO

11.

Terapia de reposição enzimática para as mucopolissacaridoses I, II e VI: recomendações de um grupo de especialistas brasileiros
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Giugliani, Roberto

; Federhen, Andressa

; Muñoz Rojas, Maria Verónica

; Vieira, Taiane Alves

; Artigalás, Osvaldo

; Pinto, Louise Lapagesse Carmargo

; Azevedo, Ana Cecília

; Acosta, Angelina Xavier

; Bomfim, Carmem

; Lourenço, Charles Marques

; Kim, Chong Ae

; Horovitz, Dafne

; Souza, Denize Bomfim

; Norato, Denise

; Marinho, Diane

; Palhares, Durval

; Santos, Emerson Santana

; Ribeiro, Erlane

; Valadares, Eugênia Ribeiro

; Guarany, Fábio

; De Lucca, Gisele Rosone

; Pimentel, Helena

; Souza, Isabel Neves de

; Corrêa Neto, Jordão

; Fraga, José Carlos

; Góes, José Eduardo

; Cabral, José Maria

; Simeonato, José

; Llerena Jr, Juan Clinton

; Jardim, Laura Bannach

; Giuliani, Liane de Rosso

; Silva, Luiz Carlos Santana da

; Santos, Mara

; Moreira, Maria Ângela

; Kerstenetzky, Marcelo

; Ribeiro, Márcia

; Ruas, Nicole

; Barrios, Patricia

; Aranda, Paulo

; Honjo, Rachel

; Boy, Raquel

; Costa, Ronaldo

; Souza, Carolina Fishinger Moura de

; Alcântara, Flavio F

; Avilla, Sylvio Gilberto A

; Fagondes, Simone

; Martins, Ana Maria

Revista da Associação Médica Brasileira

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2010, Volume 56 N. 3 Pages 271 - 277

Abstract: Pt En | Text: Pt En | PDF: Pt | PDF: En

As mucopolissacaridoses (MPS) são doenças genéticas raras causadas pela deficiência de enzimas lisossômicas específicas que afetam o catabolismo de glicosaminoglicanos (GAG). O acúmulo de GAG em vários órgãos e tecidos nos pacientes afetados pelas MPS resulta em uma série de sinais e sintomas, integrantes de um quadro clínico multissistêmico que compromete ossos e articulações, vias respiratórias, sistema cardiovascular e muitos outros órgãos e tecidos, incluindo, em alguns casos, as funções cognitivas. Já foram identificados 11 defeitos enzimáticos que causam sete tipos diferentes de MPS. Antes do advento de terapias dirigidas para a restauração da atividade da enzima deficiente, o tratamento das MPS tinha como principal foco a prevenção e o cuidado das complicações, aspecto ainda bastante importante no manejo desses pacientes. Na década de 80 foi proposto o tratamento das MPS com transplante de medula óssea/transplante de células tronco hematopoiéticas (TMO/TCTH) e na década de 90 começou o desenvolvimento da Terapia de Reposição Enzimática (TRE), que se tornou uma realidade aprovada para uso clínico nas MPS I, II e VI na primeira década do século 21. Os autores deste trabalho têm a convicção de que um melhor futuro para os pacientes afetados pelas MPS depende da identificação, compreensão e manejo adequado das manifestações multissistêmicas dessas doenças, incluindo medidas de suporte (que devem fazer parte da assistência multidisciplinar regular destes pacientes) e terapias específicas. Embora a inibição da síntese de GAG e o resgate da atividade enzimática com moléculas pequenas também possam vir a ter um papel no manejo das MPS, o grande avanço disponível no momento é a TRE intravenosa. A TRE permitiu modificar radicalmente o panorama do tratamento das mucopolissacaridoses I, II e VI na última década, sendo que ainda pode estender seus benefícios em breve para a MPS IV A (cuja TRE já está em desenvolvimento clínico), com perspectivas para o tratamento da MPS III A e do déficit cognitivo na MPS II através de administração da enzima diretamente no sistema nervoso central (SNC). Um grande número de centros brasileiros, incluindo serviços de todas as regiões do país, já têm experiência com TRE para MPS I, II e VI. Essa experiência foi adquirida não só com o tratamento de pacientes como também com a participação de alguns grupos em ensaios clínicos envolvendo TRE para essas condições. Somados os três tipos de MPS, mais de 250 pacientes já foram tratados com TRE em nosso país. A experiência dos profissionais brasileiros, somada aos dados disponíveis na literatura internacional, permitiu elaborar este documento, produzido com o objetivo de reunir e harmonizar as informações disponíveis sobre o tratamento destas doenças graves e progressivas, mas que, felizmente, são hoje tratáveis, uma realidade que traz novas perspectivas para os pacientes brasileiros afetados por essas condições.

Mucopolysaccharidoses (MPS) are rare genetic diseases caused by deficiency of specific lysosomal enzymes that affect catabolism of glycosaminoglycans (GAG). Accumulation of GAG in various organs and tissues in MPS patients results in a series of signs and symptoms, producing a multisystemic condition affecting bones and joints, the respiratory and cardiovascular systems and many other organs and tissues, including in some cases, cognitive performance. So far, eleven enzyme defects that cause seven different types of MPS have been identified. Before introduction of therapies to restore deficient enzyme activity, treatment of MPS focused primnarily on prevention and care of complications, still a very important aspect in the management of these patients. In the 80's treatment of MPS with bone marrow transplantation/hematopoietic stem cells transplantation (BMT/HSCT) was proposed and in the 90's, enzyme replacement therapy (ERT),began to be developed and was approved for clinical use in MPS I, II and VI in the first decade of the 21st century. The authors of this paper are convinced that a better future for patients affected by mucopolysaccharidoses depends upon identifying, understanding and appropriately managing the multisystemic manifestations of these diseases. This includes the provision of support measures (which should be part of regular multidisciplinary care of these patients) and of specific therapies. Although inhibition of synthesis of GAG and the recovery of enzyme activity with small molecules also may play a role in the management of MPS, the breakthrough is the currently available intravenous ERT. ERT radically changed the setting for treatment of mucopolysaccharidosis I, II and VI in the last decade., Benefits can even be extended soon to MPS IV A (ERT for this condition is already in clinical development), with prediction for treatment of MPS III A and the cognitive deficit in MPS II by administration of the enzyme directly into the central nervous system (CNS). A large number of Brazilian services, from all regions of the country, already have experience with ERT for MPS I, II and VI. This experience was gained not only by treating patients but also with the participation of some groups in clinical trials involving ERT for these conditions. Summing up the three types of MPS, more than 250 patients have already been treated with ERT in Brazil. The experience of professionals coupled to the data available in international literature, allowed us to elaborate this document, produced with the goal of bringing together and harmonize the information available for the treatment of these severe and progressive diseases, which, fortunately, are now treatable, a situation which bring new perspectives for Brazilian patients, affected by these conditions.

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12.

Teratogenic effect of retinoic acid in swiss mice
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Quemelo, Paulo Roberto Veiga

; Lourenço, Charles Marques

; Peres, Luiz Cesar

Acta Cirúrgica Brasileira

Journal Metrics
- Sobre o periódico
- SciELO Analytics

dec 2007, Volume 22 N. 6 Pages 451 - 456

Abstract: Pt En | Text: Pt En | PDF: Pt | PDF: En

OBJETIVO: Identificar os tipos de malformação resultantes da administração do ácido retinóico (AR) a camundongos Swiss em diferentes dias gestacionais. MÉTODOS: Foram utilizados 24 camundongos fêmeas, linhagem Swiss, prenhes, divididos em 4 grupos com 6 animais cada. Os grupos experimentais receberam uma única injeção intraperitoneal de AR (70mg/Kg) nos dias gestacionais 7, 8 e 9 (D7, D8 e D9), enquanto que os animais do grupo controle (C) receberam apenas solução salina. RESULTADOS: Foram encontrados: exencefalia (C:0; D7:16.1%; D8:25.4%; D9:0); mielomeningocele (C:0; D7:25.8%; D8:30.9%; D9:0); Espina Bífida Oculta (C:0; D7:29%; D8:41.8%; D90); gastrosquise (C:0; D7:6.4% D8:5.4%; D9:0); onfalocele (C:0; D7:6.4%; D8:14.5%; D9:0); alterações do membro inferior (C:0; D7:74.1%; D8:80%; D9:0); imperfuração anal (C:0; D7:100%; D8:100%; D9:100%) e agenesia/alteração de cauda (C: D7:100%; D8:100%; D9:100%). CONCLUSÕES: O modelo experimental utilizando camundongo Swiss mostrou-se eficiente na indução dos diferentes tipos de defeitos, sendo o oitavo dia gestacional o mais propicio na indução de DFTN, onfalocele, gastrosquise, defeitos de membro inferior, imperfuração anal e agenesia/alteração de cauda, tornando este um modelo útil para futuras investigações do desenvolvimento neural e no processo de formação do esqueleto apendicular.

PURPOSE: To identify the types of malformations resulting from the administration of retinoic acid (RA) to Swiss mice on different days of pregnancy. METHODS: Twenty-four pregnant Swiss mice were divided into 4 groups of 6 animals each. The experimental groups received a single intraperitoneal injection of RA (70 mg/kg) on gestational days 7, 8 and 9 (D7, D8 and D9), while control animals (C) received only saline solution. RESULTS: Were obtained: exencephaly (C:0; D7:16.1%; D8:25.4%; D9:0), myelomeningocele (C:0; D7:25.8%, D8:30.9%, D9:0), spina bifida occulta (C:0, D7:29%, D8:41.8%, D90), gastroschisis (C:0, D7:6.4% D8:5.4%, D9:0), omphalocele (C:0, D7:6.4%, D8:14.5%, D9:0), lower limb alterations (C:0, D7:74.1%, D8:80%, D9:0), imperforated anus (C:0, D7:100%, D8:100%, D9:100%), and tail agenesis/alteration (C: D7:100%, D8:100%, D9:100%). CONCLUSION: The experimental model using Swiss mice proved to be efficient in the induction of the different types of defects, with the eighth gestational day being the one that most favored the induction of neural tube defect, omphalocele, gastroschisis, lower limb defects, imperforated anus and tail agenesis/alteration. On this basis, this is a useful model for future investigation of neural development and of the formation of the appendicular skeleton.

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