Abstract Spinal muscular atrophy linked to chromosome 5 (SMA-5q) is an autosomal recessive genetic disease caused by mutations in the SMN1. SMA-5q is characterized by progressive degeneration of the spinal cord and bulbar motor neurons, causing severe motor and respiratory impairment with reduced survival, especially in its more severe clinical forms. In recent years, highly effective disease-modifying therapies have emerged, either acting by regulating the splicing of exon 7 of the SMN2 gene or adding a copy of the SMN1 gene through gene therapy, providing a drastic change in the natural history of the disease. In this way, developing therapeutic guides and expert consensus becomes essential to direct the use of these therapies in clinical practice. This consensus, prepared by Brazilian experts, aimed to review the main available disease-modifying therapies, critically analyze the results of clinical studies, and provide recommendations for their use in clinical practice for patients with SMA-5q. This consensus also addresses aspects related to diagnosis, genetic counseling, and follow-up of patients under drug treatment. Thus, this consensus provides valuable information regarding the current management of SMA-5q, helping therapeutic decisions in clinical practice and promoting additional gains in outcomes. SMA5q SMAq SMA 5q q (SMA-5q SMN neurons survival forms years diseasemodifying modifying emerged therapy way experts studies SMA5q. 5q. diagnosis counseling followup follow up treatment Thus SMA5q, 5q, outcomes

Resumo Atrofia muscular espinhal ligada ao cromossomo 5 (AME-5q) é uma doença genética de herança autossômica recessiva causada por mutações no gene SMN1. A AME-5q cursa com degeneração progressiva dos motoneurônios medulares e bulbares, acarretando grave comprometimento motor e respiratório com redução da sobrevida, especialmente nas suas formas clínicas mais graves. Nos últimos anos, terapias modificadoras da doença altamente eficazes, ou que atuam regulando o splicing do exon 7 do gene SMN2 ou adicionando uma cópia do gene SMN1 via terapia gênica, têm surgido, proporcionando uma mudança drástica na história natural da doença. Dessa forma, o desenvolvimento de guias terapêuticos e de consensos de especialistas torna-se importante no sentido de direcionar o uso dessas terapias na prática clínica. Este consenso, preparado por especialistas brasileiros, teve como objetivos revisar as principais terapias modificadoras de doença disponíveis, analisar criticamente os resultados dos estudos clínicos dessas terapias e prover recomendações para seu uso na prática clínica para pacientes com AME-5q. Aspectos relativos ao diagnóstico, aconselhamento genético e seguimento dos pacientes em uso das terapias também são abordados nesse consenso. Assim, esse consenso promove valiosas informações a respeito do manejo atual da AME-5q auxiliando decisões terapêuticas na prática clínica e promovendo ganhos adicionais nos desfechos finais. AME5q AMEq AME 5q q (AME-5q SMN bulbares sobrevida graves anos eficazes gênica surgido forma tornase torna se brasileiros disponíveis AME5q. 5q. diagnóstico Assim finais

Abstract Spinal muscular atrophy (SMA) is considered one of the most common autosomal recessive disorders, with an estimated incidence of 1 in 10,000 live births. Testing for SMA has been recommended for inclusion in neonatal screening (NBS) panels since there are several therapies available and there is evidence of greater efficacy when introduced in the pre/early symptomatic phases. In Brazil, the National Neonatal Screening Program tests for six diseases, with a new law issued in 2021 stating that it should incorporate more diseases, including SMA. In the present study, dried blood spot (DBS) samples collected by the Reference Services of Neonatal Screening of RS and SP, to perform the conventional test were also screened for SMA, using real-time PCR, with SALSA MC002 technique. A total of 40,000 samples were analyzed, enabling the identification of four positive cases of SMA, that were confirmed by MLPA. Considering our sampling, Brazil seems to have an incidence comparable to the described in other regions. This work demonstrated that the use of the MC002 technique in samples routinely collected for the conventional NBS program is suitable to screen for SMA in our conditions and can be included in the expansion of the neonatal screening programs. (SMA disorders 10000 10 000 10,00 births (NBS preearly pre early phases diseases 202 study DBS (DBS SP realtime real time PCR MC MC00 40000 40 40,00 analyzed MLPA sampling regions programs 1000 00 10,0 20 MC0 4000 4 40,0 100 0 10, 2 400 40,

Resumo Objetivo: Avaliar a segurança, a tolerabilidade e os possíveis efeitos terapêuticos do peptídeo liberador de gastrina em três crianças com transtorno do espectro autista. Métodos: Estudo de casuística com administração intravenosa de peptídeo liberador de gastrina na dose de 160 pmol/kg por quatro dias consecutivos. Para avaliar os resultados, foram usadas a impressão dos pais, a Escala de Classificação de Autismo na Infância (CARS) e a Escala de Impressão Clínica Global (CGI). Cada criança foi submetida a novo ciclo de peptídeo após duas semanas. As crianças foram acompanhadas por quatro semanas após o término das infusões. Resultados: O peptídeo liberador de gastrina foi bem tolerado e nenhuma criança apresentou efeitos adversos. Duas crianças apresentaram melhoria na interação social, com melhoria na atenção compartilhada e nas iniciativas de interação. Duas mostraram redução dos estereótipos e melhoria na linguagem verbal. Uma criança perdeu sua compulsão por banhos, efeito que durou duas semanas após cada ciclo de infusão. A redução média no escore da CARS foi de 2,8 pontos. Quanto à CGI, os resultados foram "minimamente melhor em duas crianças" e "muito melhor" em uma. Conclusões: Este estudo sugere que o peptídeo liberador de gastrina é seguro e pode ser efetivo na melhoria dos principais sintomas do transtorno do espectro autista, porém seus resultados devem ser interpretados com cautela. Ensaios clínicos controlados, randomizados, duplo-cegos e com maior número de crianças são necessários para melhor avaliar os possíveis efeitos terapêuticos do peptídeo liberador de gastrina sobre o autismo.

Abstract Objective: To evaluate the safety, tolerability and potential therapeutic effects of gastrin-releasing peptide in three children with autistic spectrum disorder. Methods: Case series study with the intravenous administration of gastrin-releasing peptide in the dose of 160 pmol/kg for four consecutive days. To evaluate the results, parental impressions the Childhood Autism Rating Scale (CARS) and the Clinical Global Impression (CGI) Scale. Each child underwent a new peptide cycle after two weeks. The children were followed for four weeks after the end of the infusions. Results: The gastrin-releasing peptide was well tolerated and no child had adverse effects. Two children had improved social interaction, with a slight improvement in joint attention and the interaction initiatives. Two showed reduction of stereotypes and improvement in verbal language. One child lost his compulsion to bathe, an effect that lasted two weeks after each infusion cycle. Average reduction in CARS score was 2.8 points. CGI was "minimally better" in two children and "much better" in one. Conclusions: This study suggests that the gastrin-releasing peptide is safe and may be effective in improving key symptoms of autism spectrum disorder, but its results should be interpreted with caution. Controlled clinical trials-randomized, double-blinded, and with more children-are needed to better evaluate the possible therapeutic effects of gastrin-releasing peptide in autism.

The evolution of autism symptoms during life were revised, from childhood to adulthood. Little information is available. After a search in PubMed, no more than 40 publications address this issue. The review was divided into two parts: a) how change the three main symptoms of autism change; b) how change the other autism-associated symptoms. The three main symptoms, called "Triad of Wing" (communication problems, social skills deficits, and a restricted repertoire of interests) do not change significantly during lifetime. The diagnosis of autism remains stable during lifetime, and 80% of children continue with this diagnosis in adulthood. Furthermore, it is difficult to establish first diagnostic of autism in adults. In relation to the associated symptoms, one of the earliest are sleep disturbances and one of the most prevalent is both bipolar and anxiety disorders. Sleep disturbances are age-limited and disappear easily. Bipolar disorders are usually more severe in children with autism when compared to children without autism. The mood transitions are faster in autistic children. Anxiety is usually more intense in cognitive preserved autistic patients and tends to increase with age. The two main prognostic factors for autism in adults are: a) total IQ above 70. b) functional language before 6 years of age.

Se ha revisado la evolución de los síntomas del autismo durante la vida, desde la niñez hasta la edad adulta. Hay poca información disponible. Después de una búsqueda en PubMed, no más de 40 publicaciones abordan específicamente este tema. La revisión fue dividida en dos partes: a) cómo cambian los tres principales síntomas del autismo; b) cómo cambian los demás síntomas asociados al autismo. Los tres síntomas, llamados la "Tríada de Wing" (problemas en la comunicación, déficits en las habilidades sociales, y un restringido repertorio de intereses) no cambian significativamente con el pasar de la vida. El diagnóstico de autismo se mantiene estable en el tiempo, ya que 80% de los niños continúan con el diagnóstico en la vida adulta. Por otro lado, es difícil establecer este diagnóstico por primera vez en los adultos. En relación a los síntomas asociados, los más precoces son los trastornos del sueño y de los más prevalentes los trastornos bipolares y también el trastorno de ansiedad. Los trastornos del sueño son edad-limitados y desaparecen fácilmente. Los trastornos bipolares suelen ser más graves en niños con autismo cuando se comparan con niños sin autismo. Las variaciones del estado de ánimo son más rápidas en niños autistas. La ansiedad suele ser más intensa en los autistas con preservación cognitiva y tiende a aumentar con la edad. Los dos principales factores pronósticos para el autismo en adultos son: a) cociente intelectual total superior a 70; b) lenguaje funcional antes de los 6 años de edad.

OBJECTIVE: To determine the clinical characteristics and the results of bronchoscopic treatment of children due to foreign body aspiration in a university hospital. METHOD: Time series of children who underwent bronchoscopies for foreign bodies aspirated into the airway between March 1993 and July 2002. Each patient was analyzed for age, sex, initial clinical diagnosis, nature and location of the foreign body, duration of symptoms between aspiration and bronchoscopy, radiological findings, results of bronchoscopic removal, complications of bronchoscopy and presence of foreign bodies in the airways. RESULTS: Thirty-four children, 20 (59%) boys, ages ranging from nine months to nine years (median = 23 months). In 32 (94%) children the foreign body was removed by rigid bronchoscope, and two resulted in thoracotomy. Foreign bodies were more frequent in children under three years of age (66%). A clinical history of foreign body inhalation was obtained in 27 (80%) cases. Most of the foreign bodies removed were organic (65%) and more frequently found in the right bronchial tree (59%). Foreign bodies were removed within 24 hours in 18 (53%) cases. The most frequent radiographic findings were: unilateral air trapping, atelectasis and radiopac foreign body. Major bronchoscopy complications occurred in seven children (22%), and there were no deaths. CONCLUSIONS: More attention is necessary to the respiratory symptoms of aspirations, mainly in boys at early ages, with clinical history and compatible radiological findings. Most foreign bodies removed were of organic nature. In this case series, therapeutic rigid bronchoscopy was effective with few complications.