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 Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rare neurodegenerative genetic disease that affects children in early life. Its classic form is rapidly progressive, leading to death within the first 10 years. The urge for earlier diagnosis increases with the availability of enzyme replacement therapy. A panel of nine Brazilian child neurologists combined their expertise in CLN2 with evidence from the medical literature to establish a consensus to manage this disease in Brazil. They voted 92 questions including diagnosis, clinical manifestations, and treatment of the disease, considering the access to healthcare in this country. Clinicians should suspect CLN2 disease in any child, from 2 to 4 years old, with language delay and epilepsy. Even though the classic form is the most prevalent, atypical cases with different phenotypes can be found. Electroencephalogram, magnetic resonance imaging, molecular and biochemical testing are the main tools to investigateand confirm the diagnosis. However, we have limited access to molecular testing in Brazil, and rely on the support from the pharmaceutical industry. The management of CLN2 should involve a multidisciplinary team and focus on the quality of life of patients and on family support. Enzyme replacement therapy with Cerliponase α is an innovative treatment approved in Brazil since 2018; it delays functional decline and provides quality of life. Given the difficulties for the diagnosis and treatment of rare diseases in our public health system, the early diagnosis of CLN2 needs improvement as enzyme replacement therapy is available and modifies the prognosis of patients. CLN (CLN2 progressive 1 9 manifestations country old epilepsy prevalent found Electroencephalogram imaging However industry 2018 system (CLN 201 20

Resumo Lipofuscinose ceróide neuronal (CLN2) é uma doença genética neurodegenerativa rara que afeta crianças nos primeiros anos de vida. A sua forma clássica é rapidamente progressiva, levando à morte nos primeiros 10 anos. A necessidade de um diagnóstico precoce aumenta com a disponibilidade do tratamento de terapia enzimática. Um painel de nove neurologistas infantis brasileiros combinou sua experiência em CLN2 com evidências da literatura médica para estabelecer um consenso no manejo desta doença no Brasil. Eles votaram 92 questões abordando diagnóstico, manifestações clínicas e tratamento, considerando o acesso à saúde no Brasil. Deve-se suspeitar de CLN2 em qualquer criança de 2 a 4 anos de idade que apresente atraso de linguagem e epilepsia. Apesar da forma clássica ser a mais prevalente, podem ser encontrados casos atípicos com diferentes fenótipos. Eletroencefalograma, ressonância magnética, testes moleculares e bioquímicos são as principais ferramentas para investigar e confirmar o diagnóstico. No entanto, o acesso aos testes moleculares é limitado no Brasil, necessitando contar com o apoio da indústria farmacêutica. O manejo da CLN2 deve envolver uma equipe multidisciplinar e focar na qualidade de vida dos pacientes e no apoio familiar. A terapia de reposição enzimática com Cerliponase alfa é um tratamento inovador aprovado no Brasil desde 2018; ele retarda o declínio funcional e proporciona qualidade de vida. Diante das dificuldades para o diagnóstico e tratamento de doenças raras em nosso sistema público de saúde, o diagnóstico precoce de CLN2 precisa de melhorias pois a terapia de reposição enzimática está disponível e modifica o prognóstico dos pacientes. CLN (CLN2 progressiva 1 9 Devese Deve se epilepsia prevalente fenótipos Eletroencefalograma magnética entanto farmacêutica familiar 2018 (CLN 201 20

Abstract Introduction Mucopolysaccharidosis (MPS) is a set of rare diseases caused by deficiency of lysosomal enzymes that lead to the accumulation of glycosaminoglycans (GAG) in tissues and organs, which, in turn, is responsible for the multisystemic clinical, chronic, and progressive symptoms. Objective To describe the profile of the otorhinolaryngological clinical examination and audiology tests of patients with MPS disease. Methods The present study is a case series. The evaluation was performed, initially, in 24 patients with MPS types I, II, IIIA, IV and VI. Results The most common hearing complaint was hearing loss, which was confirmed by audiology tests in almost 100% of the patients, most of whom presented conductive hearing loss. Conclusions It is important to evaluate the complaints, physical examination, and audiology tests in patients with MPS. The otorhinolaryngologistshould be part of the group of professionals that follows these patients to better monitor their hearing and provide early hearing rehabilitation.

Abstract Neuronal ceroid lipofuscinoses (NCLs), also referred as “Batten disease”, are a group of thirteen rare genetic conditions, which are part of the lysosomal storage disorders. CLN type 2 (CLN2) is caused by the deficient activity of the tripeptidyl peptidase I (TPP1) enzyme, encoded by the TPP1 gene, most frequently leading to the classic late infantile phenotype. Nearly 140 CLN2-causing mutations have been described. In this case report, we describe the identification of a new disease-causing mutation and highlight the importance of appropriate laboratory investigation based on clinical suspicion. The collection of dried blood spots (DBS) on filter paper, which is a convenient sample, can be used to measure the TPP1 enzyme activity and detect CLN2-related mutations. Since the biochemical and genetic diagnoses are possible and as the disease progression is fast and the therapeutic window is short, the investigation of CLN2 should be always considered when this diagnostic hypothesis is raised in order to enable the patients to benefit from the specific pharmacological treatment.

Abstract Given the lack of standardized guidance for follow-up of patients with neuronal ceroid lipofucsinosis-2 disease in Latin-American countries and the heterogeneity of the region, an expert panel was created with the participation of 11 pediatric neurologists from Colombia, Argentina, Brazil and Chile. The aim of the expert panel was to describe a framework for standardized follow-up in patients with neuronal ceroid lipofucsinosis-2 disease, on or off therapy, that could benefit patients and treating physicians alike. Experts made recommendations in the following areas: seizures, abnormal movements and ataxia, sleep disorders and pain, cognitive function, visual function, hearing and speech, cardiac function, quality of life, and motor function. Recommendations include the most appropriate tools for use in the Latin-American context and health care systems, and provide feasible follow-up guidance, applicable in public and private healthcare facilities. They take into consideration the availability of clinical assessment resources, tools (scales, questionnaires, paraclinical tests) and access to these tools in Latin-American countries, as well as other regional and local needs defined by the participating experts.

A síndrome de Joubert (SJ) é uma doença hereditária, autossômica recessiva, caracterizada por hipotonia, hipoplasia do vermis cerebelar, anormalidades oculares (p.ex., retinite pigmentar, apraxia oculomotora e nistagmo), cistos renais e fibrose hepática. Anormalidades respiratórias tais como apnéia e hiperpnéia podem estar presentes, assim como deficiência mental. Pelo menos sete loci e cinco genes diferentes associados à SJ já foram identificados. Este artigo relata cinco crianças com SJ, pertencentes a diferentes famílias. Todos os pacientes compartilham a mesma anormalidade típica da RM, conhecida como sinal do dente molar, e apresentam ampla variabilidade clínica em relação ao desempenho cognitivo, comprometimento visual e alterações extra-neurológicas.

Joubert syndrome (JS) is an autosomal recessive inherited disorder characterized by hypotonia, cerebellar vermis hypoplasia, ocular abnormalities (e.g, pigmentary retinopathy, oculomotor apraxia and nystagmus), renal cysts and hepatic fibrosis. Respiratory abnormalities, as apnea and hyperpnea, may be present, as well as mental retardation. At least seven JS loci have been determined and five genes identified. Herein, we report five children, belonging to independent families, with JS: they shared the same typical MRI abnormality, known as molar tooth sign, but had an otherwise quite variable phenotype, regarding mostly their cognitive performance, visual abilities and extra-neurological compromise.

Mais de 140 anos após a primeira descrição da ataxia de Friedreich, as ataxias autossômicas recessivas se transformaram em um dos mais complexos campos da Neurogenética. Atualmente, este grupo de doenças é composto por mais de 20 entidades clínicas e possui um número ainda maior de genes associados. Algumas doenças são muito raras, tendo sido observadas apenas em populações isoladas, enquanto que outras são encontradas no mundo todo. Um número expressivo de ataxias é tratável, e a responsabilidade em se fazer um diagnóstico correto é alta. A finalidade desta revisão é a de atualizar o neurologista a respeito dos principais aspectos clínicos e fisiopatológicos destas doenças e de apresentar um algoritmo para auxiliar a sua investigação e o seu diagnóstico.

More than 140 years after the first description of Friedreich ataxia, autosomal recessive ataxias have become one of the more complex fields in Neurogenetics. Currently this group of diseases contains more than 20 clinical entities and an even larger number of associated genes. Some disorders are very rare, restricted to isolated populations, and others are found worldwide. An expressive number of recessive ataxias are treatable, and responsibility for an accurate diagnosis is high. The purpose of this review is to update the practitioner on clinical and pathophysiological aspects of these disorders and to present an algorithm to guide the diagnosis.

Embora alguns autores não a considerem uma região endêmica, existem no Nordeste do Brasil as condições necessárias para o desenvolvimento do complexo teníase/ cisticercose. Em uma publicação prévia demosntramos no município de Mulungu do Morro, Bahia, alta soroprevalência para cisticercose em pacientes epilépticos. OBJETIVO: determinar a prevalência de teníase e sorologia positiva para cisticercose na população de Mulungu do Morro. MÉTODO: foram coletadas amostras de sangue e fezes em 175 famílias definidas aleatoriamente. A identificação de anticorpos séricos anti-cisticerco foi feita através do método de EITB e a presença de teníase foi verificada através de ELISA de captura para identificação de antígenos do parasita nas fezes. RESULTADOS: encontramos soroprevalência para cisticercose de 1,6% (IC a 95% de 0,8 a 2,8%) e prevalência de teníase de 4,5% (IC a 95% de 3,0 a 6,5%). Foi observado maior número de soropositivos nas famílias em que havia uma pessoa com teníase (p=0,007). CONCLUSÕES: nossos resultados demonstram que Mulungu do Morro é endêmico para teníase e cisticercose. Acreditamos que os demais municípios do Nordeste, cujas características socio-econômicas e condições sanitárias são semelhantes ao estudado, apresentam também alta prevalência dessa parasitose e que estudos epidemiológicos são necessários para esta definição e para que medidas de controle sejam tomadas.

Although not considered as an endemic region, the Northeast of Brazil has the necessary conditions for the development of taeniasis-cysticercosis complex. In a previous paper, we demonstrated that Mulungu do Morro municipality, in the State of Bahia, has a high seroprevalence to cysticercosis in epileptic patients. OBJECTIVE: to determine the prevalence of taeniasis and positive cysticercosis serology in the population of Mulungu do Morro. METHOD: blood and stool samples were collected from a random sampling of the population, by family. The identification of antibodies against T. solium cysticerci was made by EITB and T. solium antigens were identified using a polyclonal antibody-capture ELISA. RESULTS: the cysticercosis seroprevalence was 1.6% (C.I. = 0.8 to 2.8%) and the taeniasis prevalence 4.5% (C.I. = 3.0 to 6.5%). Seropositivity to cysticercosis was higher among those who lived in a house of a person testing positive for coproantigen, p=0.017. CONCLUSION: our results demonstrate that the taeniasis-cysticercosis complex is endemic in Mulungu do Morro. We believe that all areas in the world with the same socio-economic and sanitary characteristics are likely to have high prevalence of this parasite.

Para estudar os fatores prognósticos e incidência de complicações em meningite bacteriana, 281 crianças (idade abaixo de 13 anos) com quadro clínico e do LCR compatíveis com esse diagnóstico foram acompanhadas, durante o internamente), através de ficha de avaliação padrão. Aquelas que apresentaram sinais de lesão encefálica, resposta inadequada ao tratamento ou diminuição do nível de consciência, com Glasgow < 7, foram submetidas a tomografia computadorizada de crânio. A taxa de letalidade global foi 20,3%, sendo maior quando o agente etiológico foi identificado (23,7%). As alterações neurológicas mais encontradas foram: irritação meníngea, diminuição do nível de consciência, convulsões, irritabilidade, abaulamento de fontanela e comprometimento de nervos cranianos. Convulsões, comprometimento de nervos cranianos e ausência de irritação meníngea foram associados a maior Ietalidade. Complicações neurológicas ocorreram em 58%, sendo as mais frequentes diminuição do nível de consciência (47,7%), convulsões (22,4%), coleção subdural (3,2%), abscesso(2,5%) e hidrocefalia(2,5%). Observamos que meningite bacteriana continua sendo problema de saúde publica em países em desenvolvimento e que medidas para redução da morbidade e mortalidade desta doença são necessárias.

We studied the incidence and prognosis of acute neurologic complications in 281 children under 13 years of age with a diagnosis of acute bacterial meningitis. All the patients were examined daily by the same group of neurologists, using a standardized neurological examination. Patients with signs of encephalic lesions, unsatisfactory response to antibiotics or decreased level of consciousness were submitted to brain computer tomography. The overall lethality rate was 20.3% and cases whose causative agent was identified presented a higher lethality rate (23.7%) than those in which the agent was not found. The most important neurological abnormalities were meningeal signs (88.3%) followed by decreased consciousness (47.7%), irritability (35.2%), seizures (22.4%), fontanel bulging (20.6%) and cranial nerve palsy (14.2%). Seizures, cranial nerve palsy and the absence of meningeal signs were related to higher rates of lethality. Diminished consciousness, seizures, subdural effusion, abscess and hydrocephalus were the most important complications, respectively. We can conclude that acute bacterial meningitis continues to be an important health problem in developing countries and that public health measures will be necessary to minimize the impact of sequelae and reduce the mortality rate in children with that pathology.