Association of sociodemographic and clinical factors with the quality of life of Brazilian individuals with Neurofibromatosis type 1: a cross-sectional study

Abstract Background Neurofibromatosis type 1 (NF1) is a rare genetic disorder with a wide range of clinical manifestations, notably neurocutaneous features, that can lead to emotional and physical consequences. Objectives This study assessed the influence of sociodemographic factors and clinical features of the disease on the quality of life of Brazilian individuals with NF1. Methods This is a descriptive cross-sectional study. Data were collected from 101 individuals with NF1 using the Brazilian version of the Impact of NF1 on Quality of Life Questionnaire (INF1-QoL), a form with information on sociodemographic characteristics, and an NF1 visibility self-evaluation scale. The relationship between variables was evaluated through statistical testing, and the significance level was defined as 0.05. Results The study included 101 adults with NF1 aged 18 to 59 years, with a mean age of 35.54 years (±9.63) and a female predominance (n = 84, 83.17%). The mean total INF1-QoL score was 10.62 (±5.63), with a median of 10, minimum value of 0, and maximum of 31 points. Two characteristics of the participants were significantly associated with the quality of life: educational level (p = 0.003) and familial history of NF1 (p = 0.019). There was a statistically significant correlation between the INF1-QoL score and the degree of disease visibility (rho = 0.218; p = 0.028). Study limitations Cross-sectional study, conducted with a convenience sample and using self-reported measures. Conclusions The findings support the significant impact of NF1 on quality of life. The authors recommend multidisciplinary follow-up for patients, with adherence to anticipatory clinical care measures, adequate pain control, psychological assistance, and genetic counseling.

Mutational spectrum and genotype-phenotype correlation in Mexican patients with infantile-onset and late-onset Pompe disease.

BACKGROUND: Pompe Disease (PD) is a metabolic myopathy caused by variants in the GAA gene, resulting in deficient enzymatic activity. We aimed to characterize the clinical features and related genetic variants in a series of Mexican patients. METHODS: We performed a retrospective study of clinical records of patients diagnosed with LOPD, IOPD or pseudodeficiency. RESULTS: Twenty-nine patients were included in the study, comprising these three forms. Overall, age of symptom onset was 0.1 to 43 years old. The most frequent variant identified was c.-32-13T>G, which was detected in 14 alleles. Among the 23 different variants identified in the GAA gene, 14 were classified as pathogenic, 5 were likely pathogenic, and 1 was a variant of uncertain significance. Two variants were inherited in cis arrangement and 2 were pseudodeficiency-related benign alleles. We identified two novel variants (c.1615 G>A and c.1076-20_1076-4delAAGTCGGCGTTGGCCTG). CONCLUSION: To the best of our knowledge, this series represent the largest phenotypic and genotypic characterization of patients with PD in Mexico. Patients within our series exhibited a combination of LOPD and IOPD associated variants, which may be related to genetic diversity within Mexican population. Further population-wide studies are required to better characterize the incidence of this disease in Mexican population.

Exome Sequencing has a high diagnostic rate in sporadic congenital hypopituitarism and reveals novel candidate genes.

CONTEXT: The pituitary gland is key for childhood growth, puberty, and metabolism. Pituitary dysfunction is associated with a spectrum of phenotypes, from mild to severe. Congenital Hypopituitarism (CH) is the most commonly reported pediatric endocrine dysfunction with an incidence of 1:4000, yet low rates of genetic diagnosis have been reported. OBJECTIVE: We aimed to unveil the genetic etiology of CH in a large cohort of patients from Argentina. METHODS: We performed whole exome sequencing of 137 unrelated cases of CH, the largest cohort examined with this method to date. RESULTS: Of the 137 cases, 19.1% and 16% carried pathogenic or likely pathogenic variants in known and new genes, respectively, while 28.2% carried variants of uncertain significance. This high yield was achieved through the integration of broad gene panels (genes described in animal models and/or other disorders), an unbiased candidate gene screen with a new bioinformatics pipeline (including genes high loss of function intolerance), and analysis of copy number variants. Three novel findings emerged. First, the most prevalent affected gene encodes the cell adhesion factor ROBO1. Affected children had a spectrum of phenotypes, consistent with a role beyond pituitary stalk interruption syndrome. Second, we found that CHD7 mutations also produce a phenotypic spectrum, not always associated with full CHARGE syndrome. Third, we add new evidence of pathogenicity in the genes PIBF1 and TBC1D32, and report 13 novel candidate genes associated with CH (e.g. PTPN6, ARID5B). CONCLUSION: Overall, these results provide an unprecedented insight into the diverse genetic etiology of hypopituitarism.

Case report: A novel COL3A1 variant in a Colombian patient with isolated cerebrovascular involvement in vascular Ehlers-Danlos syndrome.

Introduction: To date, approximately 600 unique pathogenic variants have been reported in COL3A1 associated with vascular Ehlers-Danlos syndrome (vEDS). The objective of this study was to describe a patient with a novel variant in COL3A1 associated with vEDS. Case report: We describe the clinical history and thorough phenotyping of a patient with brain aneurysms and identified a novel pathogenic variant in COL3A1. This male patient reported transient focal neurologic symptoms. Physical examination showed abnormal atrophic scarring, horizontal stretch marks under the arms, and an acrogeric appearance of the skin of the hands and feet. Brain imaging revealed extensive dilation of both internal carotids and the vertebrobasilar system. Molecular analysis identified a variant in COL3A1 (NM_000090.4):c.3058G>T p.(Gly1020Cys), which was classified as likely pathogenic. Currently, the patient has never had an event concerning dissection/rupture of tissues that could be affected in this condition. Conclusion: This report demonstrates that exhaustive evaluation with clinical and genetic approaches should be considered in patients with vascular abnormalities. vEDS has a variable clinical presentation and often goes unrecognized, even though it is related to life-threatening complications and a shortened life expectancy. Diagnosis confirmed by genetic testing is crucial to determining appropriate surveillance, prevention, treatment, and genetic counseling.

Association of sociodemographic and clinical factors with the quality of life of Brazilian individuals with Neurofibromatosis type 1: a cross-sectional study.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a rare genetic disorder with a wide range of clinical manifestations, notably neurocutaneous features, that can lead to emotional and physical consequences. OBJECTIVES: This study assessed the influence of sociodemographic factors and clinical features of the disease on the quality of life of Brazilian individuals with NF1. METHODS: This is a descriptive cross-sectional study. Data were collected from 101 individuals with NF1 using the Brazilian version of the Impact of NF1 on Quality of Life Questionnaire (INF1-QoL), a form with information on sociodemographic characteristics, and an NF1 visibility self-evaluation scale. The relationship between variables was evaluated through statistical testing, and the significance level was defined as 0.05. RESULTS: The study included 101 adults with NF1 aged 18 to 59 years, with a mean age of 35.54 years (±9.63) and a female predominance (n = 84, 83.17%). The mean total INF1-QoL score was 10.62 (±5.63), with a median of 10, minimum value of 0, and maximum of 31 points. Two characteristics of the participants were significantly associated with the quality of life: educational level (p = 0.003) and familial history of NF1 (p = 0.019). There was a statistically significant correlation between the INF1-QoL score and the degree of disease visibility (rho = 0.218; p = 0.028). STUDY LIMITATIONS: Cross-sectional study, conducted with a convenience sample and using self-reported measures. CONCLUSIONS: The findings support the significant impact of NF1 on quality of life. The authors recommend multidisciplinary follow-up for patients, with adherence to anticipatory clinical care measures, adequate pain control, psychological assistance, and genetic counseling.

Quality of life of Brazilian families who have children with Fragile X syndrome: a descriptive study.

This study aimed to assess the Family Quality of Life (FQoL) of Brazilian families with male children with Fragile X syndrome (FXS). Data from 53 families were collected using forms that included sociodemographic and clinical information, as well as the Beach Center Family Quality of Life Scale, a 5-point Likert scale ranging from "very dissatisfied" (1) to "very satisfied" (5). The mean overall FQoL score was 3.56 ± 0.79; the emotional well-being domain had the lowest score (2.98 ± 1.11) and showed significant differences between the other domains: family interaction (3.81 ± 0.89; p < 0.001), parenting (3.66 ± 0.89; p < 0.001), physical and material well-being (3.48 ± 0.83; p < 0.001), and disability-related support (3.75 ± 0.98; p < 0.001). Physical and material well-being was the second-lowest domain and was statistically different from the family interaction domain (p = 0.013). Lower FQoL satisfaction ratings were found in families with children who had difficulty getting along with people of the same age (t(51) = -3.193, p = 0.002; d = 1.019) and difficulty in living together on a day-to-day basis (t(51) = -3.060, p = 0.004; d = 0.888). These results highlight the importance of proper emotional support for the family, emphasizing the need to provide assistance not only for individuals with FXS but also for other family members. Besides, we advocate for the adoption of public policies that provide financial assistance to families and the implementation of the Brazilian Policy of Comprehensive Care for People with Rare Diseases.

Estratégias de Avaliação de Tecnologias em Saúde (ATS) para medicamentos para doenças raras: uma revisão rápida de escopo / Health Technology Assessment (HTA) strategies for drugs in rare diseases: a rapid scope review

A Avaliação de Tecnologias em Saúde (ATS) considera os domínios de benefícios clínicos, perfil epidemiológico, inovação, custo-efetividade, ética e de equidade no processo de decisão dos gestores em saúde. No contexto dos medicamentos para doenças raras, é desafiador o trabalho da ATS, dada a baixa disponibilidade de evidências robustas e o alto custo unitário das tecnologias. O objetivo da revisão foi analisar as estratégias disponíveis de avaliação das demandas de incorporação de medicamentos para o tratamento de doenças raras em sistemas de saúde. Foi realizada uma revisão rápida com busca estruturada na base de dados MEDLINE (via PubMed), Cochrane Library e Health Systems Evidence. Incluíram-se estudos sobre estratégias de avaliação de medicamentos utilizados para tratamento de doenças raras. Adicionalmente, foram realizadas buscas nas Agências de ATS do Brasil, Austrália, Nova Zelândia, Canadá, Reino Unido, França, Estados Unidos e Alemanha. A síntese dos resultados foi qualitativa com o agrupamento dos achados nos seguintes eixos temáticos: Segurança e efetividade, Custo-efetividade, Impacto orçamentário e Perspectiva da sociedade. Foram identificadas 267 publicações, sendo selecionadas 16 das bases de dados indexadas e 7 da literatura cinzenta. Com a análise dos documentos, pode-se concluir que a adoção de critérios específicos harmonizada com o atual modelo de ATS é um possível caminho a ser seguido no contexto dos medicamentos para doenças raras. Concomitante a isso, abordagens no sentido de incentivo a pesquisa e produção de dados de mundo real e a criação de comitês específicos para tratativa do tema nas agências de ATS apresentam-se como alternativa para lidar com as fragilidades no contexto de doenças raras.

The Health Technology Assessment (HTA) considers evidence regarding clinical benefits, epidemiological profile, innovation, cost-effectiveness, ethics and equity in its assessment process to support managers' decisions. In the context of drugs in rare diseases, the work of the ATS is challenging given the low availability of evidence and the high cost of technologies. The objective of the review was to analyze the available strategies for evaluating the demands for incorporating drugs for the treatment of rare diseases in health systems. A rapid review was performed with a structured search in the MEDLINE database (via PubMed), the Cochrane Library and Health Systems Evidence. Studies on strategies for evaluating drugs used to treat rare diseases were included and, additionally, searches were carried out in ATS Agencies in Brazil, Australia, New Zealand, Canada, United Kingdom, France, United States and Germany. The synthesis of the results was qualitative, grouping the major ones into thematic axes: Safety and effectiveness, Cost-effectiveness, Budgetary impact and Society's perspective. 267 publications were identified, 16 selected from indexed databases and 7 from gray literature. With the analysis of the documents, it can be concluded that the adoption of specific criteria harmonized with the current ATS model is a possible path to be followed in the context of drugs for rare diseases. At the same time, approaches to encourage research and the creation of specific committees to deal with the issue in HTA agencies would complement actions towards the consolidation of this work.

The Minimum Data Set for Rare Diseases: Systematic Review.

BACKGROUND: The minimum data set (MDS) is a collection of data elements to be grouped using a standard approach to allow the use of data for clinical and research purposes. Health data are typically voluminous, complex, and sometimes too ambiguous to generate indicators that can provide knowledge and information on health. This complexity extends further to the rare disease (RD) domain. MDSs are essential for health surveillance as they help provide services and generate recommended population indicators. There is a bottleneck in international literature that reveals a global problem with data collection, recording, and structuring in RD. OBJECTIVE: This study aimed to identify and analyze the MDSs used for RD in health care networks worldwide and compare them with World Health Organization (WHO) guidelines. METHODS: The population, concept, and context methodology proposed by the Joanna Briggs Institute was used to define the research question of this systematic review. A total of 4 databases were reviewed, and all the processes were reported using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodology. The data elements were analyzed, extracted, and organized into 10 categories according to WHO digital health guidelines. The quality assessment used the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist. RESULTS: We included 20 studies in our review, 70% (n=14) of which focused on a specific health domain and 30% (n=6) of which referred to RD in general. WHO recommends that health systems and networks use standard terminology to exchange data, information, knowledge, and intelligence in health. However, there was a lack of terminological standardization of the concepts in MDSs. Moreover, the selected studies did not follow the same standard structure for classifying the data from their MDSs. All studies presented MDSs with limitations or restrictions because they covered only a specific RD, or their scope of application was restricted to a specific context or geographic region. Data science methods and clinical experience were used to design, structure, and recommend a fundamental global MDS for RD patient records in health care networks. CONCLUSIONS: Our study highlights the difficulties in standardizing and categorizing findings from MDSs for RD because of the varying structures used in different studies. The fundamental RD MDS designed in this study comprehensively covers the data needs in the clinical and management sectors. These results can help public policy makers support other aspects of their policies. We highlight the potential of our results to help strategic decisions related to RD. TRIAL REGISTRATION: PROSPERO CRD42021221593; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=221593. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1016/j.procs.2021.12.034.

Case report: A novel SON mutation in a Colombian patient with ZTTK syndrome.

Zhu-Tokita-Takenouchi-Kim syndrome is a multisystem disorder resulting from haploinsufficiency in the SON gene, which is characterized by developmental delay/intellectual disability, seizures, facial dysmorphism, short stature, and congenital malformations, primarily in the central nervous system, along with ophthalmic, dental, pulmonary, cardiologic, renal, gastrointestinal, and musculoskeletal anomalies. In this study, we describe the first Colombian patient with ZTT harboring a novel mutation that has not been previously reported and review the clinical and molecular features of previously reported patients in the literature.

Quantitative revenue estimates and qualitative assessments of innovative fundraising sources for treating rare diseases in Colombia.

Background: Like many developing countries, Colombia faces difficulties in financing health-care services as well as programs for health promotion and health education and there is evidence that its health-care system is underperforming. Objective: To provide evidence-based estimates of potential funding levels and assess the strengths, weaknesses, and viability of innovative funding mechanisms with a focus on treating rare diseases in Colombia. Methods: The strategy involved evidence-based projections of potential funding levels and a qualitative viability assessment using an expert panel. Results: Crowdfunding, corporate donation, and social impact bonds (SIBs) were deemed to be the most viable of numerous potential strategies. Expected funding levels over 10 years for rare diseases in Colombia from crowdfunding, corporate donations, and SIBs were roughly $7,200, $23,000, and $12,400, respectively. Conclusions: Based on the combination of projected funding potential along with expert consensus regarding viability and operability, crowdfunding, corporate donations, and SIBs, especially in combination, have the potential to substantially improve funding for vulnerable patient populations in Colombia.

Rarecare: A policy perspective on the burden of rare diseases on caregivers in Latin America.

In Latin America (LA), 40-50 million people live with rare diseases (RDs) that require constant monitoring, care, and attention. Caregivers help them with their basic life activities and medication administration, which they would otherwise be unable to perform. Family caregivers complement healthcare and social security systems; however, their unpaid work is often underappreciated and under-protected. Recognizing the need to address these unrecognized and undervalued women, the Americas Health Foundation (AHF) convened a panel of LA experts on caregiving for people with RDs to provide recommendations to support the undervalued family caregivers. A panel of LA experts in caregiving for RDs were given questions to address the challenges faced by family caregivers of people with RDs in LA. During a 3-day conference, the panelists' responses were discussed and edited until the panel agreed on recommendations to address the challenges. The identified challenges for caregivers included physical, emotional, and economical areas. Caregivers, primarily women, experienced physical pain, and social isolation, and were forced to pay substantial out-of-pocket expenses in their caregiving roles. Brazil and Colombia are at the forefront of policies to protect caregivers and their experiences in attempting to provide for this group are outlined as case studies for what is possible in LA. Finally, recognizing that caregivers must be included in formulating, executing, and evaluating care policies for people living with RDs and that the caregivers themselves require social assurances, the panel suggested policy objectives aimed at protecting caregivers of people living with RDs. The recommendations ranged from recognizing the role of the family caregiver as an essential supplement to the formal healthcare system to providing financial assistance, training, and workplace protection, among others. Finally, monitoring and evaluating the impact of policies is necessary to ensure that LA is moving forward in caring for family caregivers for people with RDs.

Maralixibat Treatment Response in Alagille Syndrome is Associated with Improved Health-Related Quality of Life.

OBJECTIVE: The objective of this study was to assess the impact of treatment response to the ileal bile acid transporter inhibitor maralixibat on health-related quality of life (HRQoL) in children with Alagille syndrome. STUDY DESIGN: This analysis used data from the ICONIC trial, a phase 2 study with a 4-week double-blind, placebo-controlled, randomized drug withdrawal period in children with Alagille syndrome with moderate-to-severe pruritus. Clinically meaningful treatment response to maralixibat was defined a priori as a ≥1-point reduction in the Itch-Reported Outcome (Observer) score, from baseline to week 48. HRQoL was assessed using the Pediatric Quality of Life Inventory Generic Core, Family Impact, and Multidimensional Fatigue scale scores, which were collected via the caregiver. The minimal clinically important difference for HRQoL ranged from 4 to 5 points, depending on the scale. RESULTS: Twenty of the 27 patients (74%) included in this analysis achieved an Itch-Reported Outcome (Observer) treatment response at week 48. The mean (SD) change in Multidimensional Fatigue score was +25.8 (23.0) for responders vs -3.1 (19.8) for nonresponders (P = .03). Smaller and non-statistically significant mean changes were observed for the Pediatric Quality of Life Inventory Generic Core and Family Impact scores. Controlling for baseline Family Impact score, responders' Family Impact scores increased an average of 16.9 points over 48 weeks compared with non-responders (P = .05). Smaller and non-statistically significant point estimates were observed for the Pediatric Quality of Life Inventory Generic Core and Multidimensional Fatigue scores. CONCLUSION: The significant improvements in pruritus seen with maralixibat at week 48 of the ICONIC study are clinically meaningful and are associated with improved HRQoL. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02160782.

Coincidencia de Rhupus y embarazo. Reporte de caso / Coincidence of Rhupus and pregnancy. Case report

Resumen ANTECEDENTES: Si bien el lupus eritematoso sistémico y la artritis reumatoide son enfermedades suficientemente descritas, no lo es la asociación de estas, que se denomina rhupus, que hace referencia a la manifestación clínica resultante de ambas enfermedades enmascaradas que dificulta el diagnóstico y tratamiento. CASO CLÍNICO: Paciente de 37 años que inició con un cuadro con características de lupus eritematoso sistémico y artritis reumatoide hacía 16 años. Se encontró con alteraciones en los estudios de laboratorio y con hallazgos radiológicos que apoyaron el cuadro de rhupus. Por lo anterior se documenta la evolución de este padecimiento, que coincide con su embarazo y después de éste. CONCLUSIONES: La aparición simultánea de lupus eritematoso sistémico y artritis reumatoide, aun cuando fue reportada desde hace décadas, es una enfermedad rara en frecuencia, por lo que hay escasa información del rhupus solo y más aún en coincidencia con el embarazo.

Abstract BACKGROUND: Although systemic lupus erythematosus and rheumatoid arthritis are sufficiently described diseases, the association of these is not, and is called rhupus, which refers to the clinical manifestation resulting from both diseases masked, making diagnosis and treatment difficult. CLINICAL CASE: 37-year-old patient who started with a clinical picture with features of systemic lupus erythematosus and rheumatoid arthritis 16 years ago. She was found to have alterations in laboratory studies and radiological findings that supported the diagnosis of rheupus. Therefore, the evolution of this condition is documented, which coincides with and after her pregnancy. CONCLUSIONS: The simultaneous occurrence of systemic lupus erythematosus and rheumatoid arthritis, even though it was reported decades ago, is a rare disease in frequency, so there is scarce information on rhupus alone and even more so in coincidence with pregnancy.

Unusual presentation of Loeys-Dietz syndrome: A case report of clinical findings and treatment challenges.

BACKGROUND: Loeys-Dietz syndrome (LDS) is a rare autosomal dominant syndrome characterized by heterozygous mutations causing multisystemic alterations. It was recently described in 2005, and today at least six different subtypes have been identified. Classically presenting with aortic root enlargement or aneurysms and craniofacial and skeletal abnormalities, with specific arterial tortuosity at any site. The differential diagnosis of LDS includes atypical Marfan syndrome, vascular Ehlers-Danlos syndrome, Shprintzen-Goldberg craniosynostosis, and familial aortic aneurysm and dissection syndrome. CASE SUMMARY: We present a case study of a 35-year-old female who came to the emergency department due to lower gastrointestinal bleeding and severe abdominal pain. Computed tomography revealed vascular tortuosity in almost every abdominal vein. CONCLUSION: This case report will help us analyze the infrequent presentation of LDS type 4 and the numerous complications that it implies, underlying the importance of publishing more cases in order to expand our knowledge and offer better treatment for these patients. Differential diagnosis, clinical presentation and treatment options for this syndrome are discussed in this article.

Protocolo de lavado pulmonar total del Hospital Santa Clara de Bogotá, a propósito de una paciente con proteinosis alveolar pulmonar resistente / Whole Lung Lavage Protocol at Hospital Santa Clara of Bogotá: Presentation of a Patient with Resistant Pulmonary Alveolar Proteinosis

RESUMEN La proteinosis alveolar pulmonar es una entidad clínica caracterizada por la acumula ción de material proteináceo, con alta riqueza en surfactante, mediado por una menor aclaración por parte de los macrófagos alveolares. En pacientes adultos, comúnmente se asocia a fenómenos autoinmunes que tienen como resultado una deficiencia del factor estimulante de colonias de granulocitos y macrófagos, lo que implica alteracio nes en la maduración y disfunción celular, lo que provoca disminución de la degrada ción del surfactante y su acumulación en el espacio alveolar. Su diagnóstico corres ponde a un reto para el clínico, sobre la base de los hallazgos en pruebas de función pulmonar, el patrón en "empedrado" (crazy paving) en la tomografía computarizada de tórax de alta resolución y que se confirma al obtener el material proteináceo en el lava do broncoalveolar. Dada su rareza, el tratamiento ideal permanece por ser elucidado y en la actualidad el pilar del tratamiento es el lavado pulmonar total. Reportamos un caso anecdótico de una paciente de 41 años con proteinosis alveolar pulmonar desde 2011, que ha requerido múltiples lavados pulmonares totales, con pobre respuesta a estos, persistencia de disnea y necesidad de oxígeno suplementario a pesar de realizar el procedimiento, pero con tendencia progresiva a la mejoría en los últimos 2 años. La técnica del lavado no está completamente estandarizada y su uso en Amé rica Latina es aún limitado, por lo que publicamos el protocolo utilizado en el Hospital Santa Clara de Bogotá, Colombia.

ABSTRACT Pulmonary alveolar proteinosis is a clinical entity characterized by the accumulation of proteinaceous material, rich in surfactant, mediated by reduced clearance by alveolar macrophages. In adult patients, it is commonly associated with autoimmune phenom ena resulting in a deficiency of the granulocyte-macrophage colony stimulating factor, which implies alterations in cell maturation and dysfunction, causing a decrease in surfactant degradation and its accumulation in the alveolar space. Its diagnosis poses a challenge to the clinician, based on the findings of pulmonary function tests and the crazy paving pattern of the high-resolution computed tomography of the chest, and is confirmed by obtaining the proteinaceous material in the bronchoalveolar la vage. Given its rarity, the ideal treatment remains to be elucidated, with whole lung lavage currently being the cornerstone of treatment. We report an anecdotal case of a 41-year-old female patient suffering from pulmonary alveolar proteinosis since 2011, who has required multiple whole lung lavages, with poor response to these, with persistent dyspnea and supplemental oxygen requirement even though she has performed the procedure, but with a progressive tendency towards improvement in the last 2 years. The lavage technique is not completely standardized and its use in Latin America is still limited, which is why we publish the protocol used in the Hospital Santa Clara of Bogotá, Colombia.

Tumor neuroectodérmico primitivo periférico de riñón, reporte de caso

Introducción: El tumor neuroectodérmico primitivo periférico de riñón (PNETk) es una enfermedad rara muy agresivo que afecta mayormente a varones jóvenes. Reporte de caso: paciente varón de 19 años con cuadro clínico dolor abdominal, hematuria y masa palpable, en la tomografía se evidencia una enorme tumoración renal izquierda, Se le realiza nefrectomía radical convencional y se envía a estudio patológico más histoquímica resultando de PNETk. Luego paciente siguió su manejo por oncología para quimiterapia inicialmente. Conclusión: El PNETk que describimos representa el primer caso reportado en nuestro país, constituye una entidad clínica única por su rareza siendo un reto hacer diagnóstico y su comportamiento y manejo se sigue basando a reportes de casos debido a su poca frecuencia.

Introduction: Peripheral primitive neuroectodermal tumor of the kidney (PNETk) is a very aggressive rare disease that mainly affects young men. Case report: A 19-year-old male patient with symptoms of abdominal pain, hematuria and a palpable mass, the tomography shows a large left renal tumor. Conventional radical nephrectomy was performed and sent for pathology study plus histochemistry, resulting in PNETk. The patient then continued his oncology management for chemotherapy initially. Conclusion: The PNETk that we describe represents the first case reported in our country, it constitutes a unique clinical entity due to its rarity, being a challenge to make a diagnosis and its behavior and management is still based on case reports due to its infrequency.

Novel frameshift mutation in LIS1 gene is a probable cause of lissencephaly: a case report.

BACKGROUND: Lissencephaly (LIS) is a cortical malformation, characterized by smooth or nearly smooth cerebral surface and a shortage of gyral and sulcal development, which is caused by deficient neuronal migration during embryogenesis. Neuronal migration involves many gene products, among which is the product of the PAFAH1B1 gene, associated with this disease. LIS is a rare disease, characterized by low population frequency, and with non-specific clinical symptoms such as early epilepsy, developmental delay or cerebral palsy-like motor problems. Given that high-throughput sequencing techniques have been improving diagnosis, we have chosen this technique for addressing this patient. CASE PRESENTATION: We present the case of a seven years old male patient with an undiagnosed rare disease, with non-specific clinical symptoms possibly compatible with lissencephaly. The patient was enrolled in a study that included the sequencing of his whole genome. Sequence data was analyzed following a bioinformatic pipeline. The variants obtained were annotated and then subjected to different filters for prioritization. Also mitochondrial genome was analyzed. A novel candidate frameshift insertion in known PAFAH1B1 gene was found, explaining the index case phenotype. The assessment through in silico tools reported that it causes nonsense mediated mechanisms and that it is damaging with high confidence scores. The insertion causes a change in the reading frame, and produces a premature stop codon, severely affecting the protein function and probably the silencing of one allele. The healthy mother did not carry the mutation, and the unaffected father was not available for analysis. CONCLUSIONS: Through this work we found a novel de novo mutation in LIS1/PAFAH1B1 gene, as a likely cause of a rare disease in a young boy with non-specific clinical symptoms. The mutation found correlates with the phenotype studied since the loss of function in the gene product has already been described in this condition. Since there are no other variants in the PAFAH1B1 gene with low population frequency and due to family history, a de novo disease mechanism is proposed.