Primer caso reportado en Panamá de: Síndrome de Baraitser Winter

El síndrome cerebro-frontal-facial de Baraitser-Winter (BWCFF) se origina a partir de mutaciones sin sentido, heterocigóticas, en uno de los dos genes ubicuos que codifican la actina citoplásmica, ya sea ACTB o ACTG1. Este síndrome es una combinación de malformaciones faciales y cerebrales. Entre las malformaciones faciales que podemos observar, destacan el coloboma de iris, la ptosis bilateral, el hipertelorismo, el puente nasal ancho y los pliegues epicánticos prominentes. Las malformaciones cerebrales incluyen la paquigiria, la heterotopia de banda subcortical y las anomalías del cuerpo calloso. En este contexto, presentamos el caso de una niña de 11 años que presentaba algunos rasgos faciales distintivos, además de malformaciones cerebrales, baja estatura, discapacidad cognitiva moderada, y retraso del habla y lenguaje. Mediante secuenciación por exoma clínico dirigido, se identificó una variante sin sentido heterocigota de Novo en ACTB: c.617G>A (p. Arg206Gln). (provisto por Infomedic International)

The Baraitser-Winter cerebral-front-facial syndrome (BWCFF) is caused by heterozygous nonsense mutations in one of the two ubiquitous genes encoding cytoplasmic actin, either ACTB or ACTG1. The syndrome combines facial and cerebral malformations. Among the facial malformations that can be observed are iris coloboma, bilateral ptosis, hypertelorism, broad nasal bridge, and prominent epicanthic folds. The cerebral malformations include pachygyria, subcortical band heterotopia, and anomalies of the corpus callosum. We present the case of an 11-year-old girl who had some distinctive facial features, as well as cerebral malformations, short stature, moderate cognitive disability, and speech and language delay. Targeted clinical exome sequencing identified a heterozygous de novo nonsense variant in ACTB: c.617G>A (p. Arg206Gln). (provided by Infomedic International)

Conocimiento de las enfermedades genéticas raras en la práctica clínica diaria

En este número, nos complace presentar 4 trabajos multidisciplinarios que incluyen disciplinas como la Genética Pediátrica, la Hematología, y Nefrología.  Estos trabajos de gran calidad representan el esfuerzo de meses de los colegas especialistas en el área de la genética clínica multidisciplinaria. Cada contribución representa una herramienta para la educación y la docencia a múltiples niveles del aprendizaje médico. (provisto por Infomedic International)

In this issue, we are pleased to present 4 multidisciplinary papers that include disciplines such as Pediatric Genetics, Hematology, and Nephrology. These high quality papers represent the efforts of months of specialist colleagues in the area of multidisciplinary clinical genetics. Each contribution represents a tool for education and teaching at multiple levels of medical learning. (provided by Infomedic International)

Gyrate atrophy of the choroid and retina: Update on diagnosis and treatment.

Gyrate atrophy of the choroid and retina (GACR) is a rare autosomal recessive disease characterised by elevated plasma ornithine levels due to deficiency of the enzyme ornithine aminotransferase (OAT). The accumulation of this amino acid in plasma leads to the development of patches of chorioretinal atrophy in the peripheral retina extending into the macular area. Patients usually present with night blindness followed by constriction of the visual field and, finally, decreased central vision and blindness. The disease is diagnosed by the presence of the characteristic clinical picture, the presence of hyperornithinaemia in plasma and the detection of mutations in the OAT enzyme gene. There is currently no effective gene therapy and the most common therapeutic intervention mainly involves dietary modifications with arginine restriction. This article aims to summarise the pathogenesis, clinical and diagnostic findings and treatment options in patients with GACR.

Alpha-1 antitrypsin deficiency

Alpha-1 antitrypsin deficiency (AATD) is a rare hereditary condition caused by decreased plasma and tissue levels of alpha-1 antitrypsin (AAT) that can lead to serious lung and liver disease in children and adults. AATD patients face challenges such as under diagnosis, clinical variability, and limited treatment options for liver disease. Early detection and biomarkers for predicting outcomes are needed to improve patient outcome. Currently, the only approved pharmacological therapy is augmentation therapy, which can delay the progression of emphysema. However, alternative strategies such as gene therapy, induced pluripotent stem cells, and prevention of AAT polymerization inside hepatocytes are being investigated. This review aims to summarize and update current knowledge on AATD, identify areas of controversy, and formulate questions for further research. (AU)

El déficit de alfa-1 antitripsina (DAAT) es una enfermedad hereditaria poco frecuente causada por la disminución de los niveles plasmáticos y tisulares de alfa-1 antitripsina (AAT) que puede provocar enfermedades pulmonares y hepáticas graves en niños y adultos. Aquellos con DAAT se enfrentan a retos como el infradiagnóstico, la variabilidad clínica y a las limitadas opciones de tratamiento para la enfermedad hepática. La detección precoz y los biomarcadores para predecir los resultados clínicos son necesarios para mejorar la evolución de los pacientes. En la actualidad, el único tratamiento farmacológico aprobado es la terapia de reposición, que puede retrasar la progresión del enfisema. Sin embargo, se están investigando estrategias alternativas como la terapia génica, las células madre pluripotentes inducidas y la prevención de la polimerización de la AAT en el interior de los hepatocitos. Esta revisión pretende resumir y actualizar los conocimientos actuales sobre la AATD, identificar las áreas de controversia y formular preguntas para futuras investigaciones. (AU)

Controles de calidad externos en el diagnóstico molecular de enfermedades genéticas. Impacto sobre la calidad de los estudios genéticos / External quality controls in the molecular diagnosis of genetic diseases. Impact on the quality of the genetic studies / Controles de qualidade externos no diagnóstico molecular de doenças genéticas. Impacto na qualidade dos estudos genéticos

Resumen La participación en programas de evaluación externa de la calidad (PEEC) dirigidos al diagnóstico de enfermedades genéticas permite obtener una medida objetiva del desempeño técnico y analítico de los laboratorios y es un requisito para la acreditación de los laboratorios clínicos bajo la norma ISO 15189. El objetivo de este estudio fue evaluar retrospectivamente el desempeño en los esquemas EMQN (European Molecular Genetics Quality Network) y CF Network (Cystic Fibrosis European Network) en el período 2014-2022. Se participó en un total de 88 esquemas. Se recolectó la información de nuestros puntajes y las medias de los laboratorios participantes en las categorías genotipificación, interpretación y exactitud de la información del paciente/informe. Se informó en forma completa el 90,9% (n=80) de los esquemas. El desempeño en genotipificación mostró puntajes superiores a la media en el 89,3% de los esquemas; 0,8% de los informes correspondieron a falsos negativos. En interpretación, el 66,7% de los esquemas evidenció un desempeño superior a la media y el 33,3% debajo de la media. La exactitud de la información del paciente/informe presentó puntajes superiores a la media en el 97,6% de los esquemas. Se observó una diferencia estadísticamente significativa en el porcentaje de esquemas con puntaje por encima de la media en el año 2022 (10/12 esquemas) respecto al año 2014 (1/6 esquemas) en la categoría interpretación (p=0,0128). En conclusión, la participación regular en PEEC tuvo impacto positivo en la calidad de los estudios y permite realizar mejoras continuas a partir de las recomendaciones sugeridas por estos programas.

Abstract Participation in external quality assessment programmes focused on rare genetic diseases makes it possible to assess the laboratory technical and analytical performance and it is a prerequisite for accreditation according to ISO 15189. The objective of this study was to perform a retrospective evaluation of our performance in the EMQN (European Molecular Genetics Quality Network) and the CF Network (Cystic Fibrosis European Network) programmes in the 2014-2022 period. The laboratory performance on genotyping, interpretation and clerical accuracy and patient identifiers in a total of 88 schemes were assessed. The information of our scores and the mean scores of all participating laboratories in the three categories were collected. A total of 90.9% of the schemes were fully completed. The performance in genotyping showed scores above the mean scores in 89.3% of the schemes; 0.8% of the reports correspond to false negative results. Regarding interpretation category, 66.7% of the schemes presented scores above the mean scores and 33.3% below the mean scores. The clerical accuracy and patient identifiers were above the mean scores in 97.6% of the schemes. A statistically significant difference in the percentage of schemes with a score above the mean for the interpretation category in the year 2022 (10/12 schemes) was observed compared to the year 2014 (1/6 schemes) (p=0.0128). In conclusion, regular participation in external quality assessment programmes had a positive impact on the quality of the studies and allows for continuous improvements based on the recommendations suggested by these programmes.

Resumo A participação em programas de avaliação externa da qualidade (PEECs) voltados para o diagnóstico de doenças genéticas permite obter uma mensuração objetiva do desempenho técnico e analítico dos laboratórios e é requisito para a acreditação dos laboratórios clínicos sob a norma ISO 15189. O objetivo desse estudo foi avaliar retrospectivamente o desempenho nos esquemas EMQN (European Molecular Genetics Quality Network) e CF Network (Cystic Fibrosis European Network) no período 2014-2022. Participou-se em um total de 88 esquemas. Foram coletadas informações de nossos escores e das médias dos laboratórios participantes nas categorias genotipagem, interpretação e precisão da informação do paciente/laudo. 90,9% (n=80) dos esquemas foram informados em sua totalidade. O desempenho na genotipagem apresentou escores acima da média em 89,3% dos esquemas; 0,8% dos laudos corresponderam a falsos negativos. Na interpretação, 66,7% dos esquemas apresentaram desempenho acima da média e 33,3% abaixo da média. A precisão das informações do paciente/laudo apresentou escores acima da média em 97,6% dos esquemas. Observou-se diferença estatisticamente significativa no percentual de esquemas com pontuação acima da média no ano de 2022 (10/12 esquemas) em relação ao ano de 2014 (1/6 esquemas) na categoria interpretação (p=0,0128). Em conclusão, a participação regular em PEECs teve um impacto positivo na qualidade dos estudos e permite fazer melhorias contínuas com base nas recomendações sugeridas por esses programas.

The importance of data in Pulmonary Arterial Hypertension: from international registries to Machine Learning. / La importancia de los datos en la hipertensión arterial pulmonar: de los registros internacionales al machine learning.

Real-world registries have been critical to building the scientific knowledge of rare diseases, including Pulmonary Arterial Hypertension (PAH). In the past 4 decades, a considerable number of registries on this condition have allowed to improve the pathology and its subgroups definition, to advance in the understanding of its pathophysiology, to elaborate prognostic scales and to check the transferability of the results from clinical trials to clinical practice. However, in a moment where a huge amount of data from multiple sources is available, they are not always taken into account by the registries. For that reason, Machine Learning (ML) offer a unique opportunity to manage all these data and, finally, to obtain tools that may help to get an earlier diagnose, to help to deduce the prognosis and, in the end, to advance in Personalized Medicine. Thus, we present a narrative revision with the aims of, in one hand, summing up the aspects in which data extraction is important in rare diseases -focusing on the knowledge gained from PAH real-world registries- and, on the other hand, describing some of the achievements and the potential use of the ML techniques on PAH.

Presencia de buenas prácticas de humanización en la atención a los pacientes con enfermedades raras en los servicios de farmacia / Presence of good humanization practices in the healthcare of patients with rare diseases in Pharmacy Services

Objetivo analizar la presencia de buenas prácticas de humanización en la atención a los pacientes con enfermedades raras en los servicios de farmacia hospitalaria para identificar las fortalezas y las áreas prevalentes de mejora para una atención más humanizada. Métodos se elaboró un cuestionario online empleando Google Form® estructurado en 2 partes: la primera recogía datos identificativos y la segunda incluía las preguntas relacionadas con el cumplimiento de los 61 estándares del Manual de buenas prácticas de humanización en la atención a pacientes con enfermedades raras en los servicios de farmacia hospitalaria. El acceso al cuestionario se envió por correo electrónico a los jefes de servicio de farmacia hospitalaria de 18 hospitales. El periodo de estudio fue de octubre 2021 a octubre 2022. Las variables analizadas fueron el número de criterios cumplidos, el cumplimiento total (porcentaje de criterios cumplidos) tanto por línea estratégica como por tipo o nivel de estándar (básico, básico de obligado cumplimiento, avanzado o excelente), de forma global y agrupados por comunidades autónomas. Resultados el estudio incluyó 18 servicios de farmacia hospitalaria. La media global de estándares cumplidos fue de 31,1 (IC 95%: 24,8–37,6) y el cumplimiento total medio del 52,1% (IC 95%: 44,4–59,7). La línea 1, Cultura de humanización, tuvo un cumplimiento medio del 46,5% (IC 95%: 35,3–57,7), la línea 2, Empoderamiento del paciente, del 47,4% (IC 95%: 37,1–57,8), la línea 3, Cuidado del profesional, del 49,7% (IC 95%: 39,8–59,1), la línea 4, Espacios físicos y confort del 55,6% (IC 95%: 46,3–64,8) y la línea 5, Organización de la atención, del 63,8% (IC 95%: 55,8–71,9). Conclusión el cumplimiento medio de los estándares está entre 40 y 60%, lo que indica que la humanización está presente en los servicios de farmacia hospitalaria, pero existe un amplio margen de mejora (AU)

Objective To analyze the presence of Good Humanization Practices in the care of patients with rare diseases in Hospital Pharmacy Services and to identify the strengths and prevalent areas for improvement in the humanization of healthcare. Methods Online questionnaire structured in two parts was developed using Google Form®. The first one was designed to collect identifying data and the second one included questions related to compliance with the 61 standards of the Manual of Good Humanization Practices in the healthcare of patients with rare diseases in Hospital Pharmacy Services. Access to the questionnaire was sent by email to the Heads of the Hospital Pharmacy Service of 18 hospitals. The study period was from October 2021 to October 2022. The analyzed variables were the number of criteria that were considered met, total compliance (percentage of criteria met), by strategic line and by type or level of standard, globally and grouped by regions of Spain. Results 18 Hospital Pharmacy Services were included. The overall mean of standards met was 31.1 (95% CI: 24.8–37.6) and mean total compliance was 52.1% (95% CI: 44.4–59.7). The mean compliance by strategic line was line 1 Humanization culture: 46.5% (95% CI: 35.3–57.7), line 2 Patient empowerment: 47.4% (95% CI: 37.1– 57.8), line 3 Professional care: 49.7% (95% CI: 39.8–59.1), line 4 Physical spaces and comfort: 55.6% (95% CI: 46.3–64.8) and line 5 Organization of healthcare: 63.8% (95% CI: 55.8–71.9). Conclusion The average compliance with the standards is between 40 and 60%, which indicates that humanization is present in the Hospital Pharmacy Services, but there is a wide margin for improvement. The main strength in the humanization of Hospital Pharmacy Services is a patient-centered care organization, and the area with the greatest room for improvement is the culture of humanization (AU)

Relaciones afectivas y calidad de vida en el ámbito de las enfermedades raras: una revisión sistemática / Affective Relationships and Quality of Life in Rare Diseases: A Systematic Review

La calidad de vida en pacientes y cuidadores no puede ser concebida sin incluir a las necesidades sociales. El objetivo de esta investigación es realizar una revisión sistemática que muestre evidencias empíricas de cómo influyen las relaciones afectivas en la calidad de vida de pacientes con enfermedades raras y sus cuidadores. Se realizó una búsqueda en las bases de datos Web of Science, Scopus y PsycInfo. Se encontraron 4923 artículos que tras el proceso de cribado quedaron reducidos a 12 estudios. Se hallaron efectos de las relaciones afectivas tanto el núcleo familiar como en sus componentes de forma independiente (padres, hermanos y pacientes). Se evidencia que tanto el ámbito familiar como extrafamiliar son esenciales para abordar una mejora de la calidad de vida. Se recomienda en futuras investigaciones el estudio de las interacciones entre las relaciones establecidas para poder ofrecer una mejor intervención . (AU)

Quality of life in patients and caregivers cannot be conceived without including social needs. The aim of this research is to conduct a systematic review showing empirical evidence of how affective relationships influence the quality of life of patients with rare diseases and their caregivers. A search was conducted in the Web of Science, Scopus and PsycInfo databases. A total of 4923 articles were found, which after the screening process were reduced to 12 studies. The effects of affective relationships were found both in the family nucleus and in its components independently (parents, siblings and patients). It is evident that both the family and the extra-familial environment are essential to improve quality of life. It is recommended that future research should study the interactions between the established relationships to offer a better intervention. (AU)

Relaciones afectivas y calidad de vida en el ámbito de las enfermedades raras: una revisión sistemática / Affective Relationships and Quality of Life in Rare Diseases: A Systematic Review

La calidad de vida en pacientes y cuidadores no puede ser concebida sin incluir a las necesidades sociales. El objetivo de esta investigación es realizar una revisión sistemática que muestre evidencias empíricas de cómo influyen las relaciones afectivas en la calidad de vida de pacientes con enfermedades raras y sus cuidadores. Se realizó una búsqueda en las bases de datos Web of Science, Scopus y PsycInfo. Se encontraron 4923 artículos que tras el proceso de cribado quedaron reducidos a 12 estudios. Se hallaron efectos de las relaciones afectivas tanto el núcleo familiar como en sus componentes de forma independiente (padres, hermanos y pacientes). Se evidencia que tanto el ámbito familiar como extrafamiliar son esenciales para abordar una mejora de la calidad de vida. Se recomienda en futuras investigaciones el estudio de las interacciones entre las relaciones establecidas para poder ofrecer una mejor intervención . (AU)

Quality of life in patients and caregivers cannot be conceived without including social needs. The aim of this research is to conduct a systematic review showing empirical evidence of how affective relationships influence the quality of life of patients with rare diseases and their caregivers. A search was conducted in the Web of Science, Scopus and PsycInfo databases. A total of 4923 articles were found, which after the screening process were reduced to 12 studies. The effects of affective relationships were found both in the family nucleus and in its components independently (parents, siblings and patients). It is evident that both the family and the extra-familial environment are essential to improve quality of life. It is recommended that future research should study the interactions between the established relationships to offer a better intervention. (AU)

Presence of good humanization practices in the healthcare of patients with rare diseases in Pharmacy Services. / Presencia de buenas prácticas de humanización en la atención a los pacientes con enfermedades raras en los servicios de farmacia.

OBJECTIVE: To analyze the presence of Good Humanization Practices in the care of patients with rare diseases in Hospital Pharmacy Services and to identify the strengths and prevalent areas for improvement in the humanization of healthcare. METHODS: Online questionnaire structured in two parts was developed using Google Form®. The first one was designed to collect identifying data and the second one included questions related to compliance with the 61 standards of the Manual of Good Humanization Practices in the healthcare of patients with rare diseases in Hospital Pharmacy Services. Access to the questionnaire was sent by email to the Heads of the Hospital Pharmacy Service of 18 hospitals. The study period was from October 2021 to October 2022. The analyzed variables were the number of criteria that were considered met, total compliance (percentage of criteria met), by strategic line and by type or level of standard, globally and grouped by regions of Spain. RESULTS: 18 Hospital Pharmacy Services were included. The overall mean of standards met was 31.1 (95% CI: 24.8-37.6) and mean total compliance was 52.1% (95% CI: 44.4-59.7). The mean compliance by strategic line was line 1 Humanization culture: 46.5% (95% CI: 35.3-57.7), line 2 Patient empowerment: 47.4% (95% CI: 37.1- 57.8), line 3 Professional care: 49.7% (95% CI: 39.8-59.1), line 4 Physical spaces and comfort: 55.6% (95% CI: 46.3-64.8) and line 5 Organization of healthcare: 63.8% (95% CI: 55.8-71.9). CONCLUSION: The average compliance with the standards is between 40 and 60%, which indicates that humanization is present in the Hospital Pharmacy Services, but there is a wide margin for improvement. The main strength in the humanization of Hospital Pharmacy Services is a patient-centered care organization, and the area with the greatest room for improvement is the culture of humanization.

Alpha-1 antitrypsin deficiency.

Alpha-1 antitrypsin deficiency (AATD) is a rare hereditary condition caused by decreased plasma and tissue levels of alpha-1 antitrypsin (AAT) that can lead to serious lung and liver disease in children and adults. AATD patients face challenges such as under diagnosis, clinical variability, and limited treatment options for liver disease. Early detection and biomarkers for predicting outcomes are needed to improve patient outcome. Currently, the only approved pharmacological therapy is augmentation therapy, which can delay the progression of emphysema. However, alternative strategies such as gene therapy, induced pluripotent stem cells, and prevention of AAT polymerization inside hepatocytes are being investigated. This review aims to summarize and update current knowledge on AATD, identify areas of controversy, and formulate questions for further research.

[Translated article] Good humanisation practices in the healthcare of patients with rare diseases in Pharmacy Services.

OBJECTIVE: To analyse the presence of Good Humanisation Practices in the care of patients with rare diseases in Hospital Pharmacy Services and to identify the strengths and prevalent areas for improvement in the humanisation of healthcare. METHODS: An online questionnaire structured in 2 parts was developed using Google Form®. The first one was designed to collect identifying data and the second one included questions related to compliance with the 61 standards of the Manual of Good Humanisation Practices in the healthcare of patients with rare diseases in Hospital Pharmacy Services. Access to the questionnaire was sent by email to the Heads of the Hospital Pharmacy Service of 18 hospitals. The study period was from October 2021 to October 2022. The analysed variables were the number of criteria that were considered met, total compliance (percentage of criteria met), by strategic line and by type or level of standard, globally and grouped by regions of Spain. RESULTS: 18 Hospital Pharmacy Services were included. The overall mean of standards met was 31.1 (95% CI: 24.8-37.6) and mean total compliance was 52.1% (95% CI: 44.4%-59.7%). The mean compliance by strategic line was: Line 1, Humanisation culture: 46.5% (95% CI: 35.3%-57.7%), Line 2, Patient empowerment: 47.4% (95% CI: 37.1%-57.8%), Line 3, Professional care: 49.7% (95% CI: 39.8%-59.1%), Line 4, Physical spaces and comfort: 55.6% (95% CI: 46.3%-64.8%), and Line 5, Organisation of healthcare: 63.8% (95% CI: 55.8%-71.9%). CONCLUSION: The average compliance with the standards is between 40% and 60%, which indicates that humanisation is present in the Hospital Pharmacy Services, but there is a wide margin for improvement. The main strength in the humanisation of Hospital Pharmacy Services is a patient-centred care organisation, and the area with the greatest room for improvement is the culture of humanisation.

Enfermedades raras con crisis epilépticas / Rare diseases with epileptic seizures

Las enfermedades raras (ER) con epilepsia son un grupo heterogéneo de entidades en las que existe frecuentemente una causa genética. En una mayoría de casos, la epilepsia que aparece en estos pacientes puede encuadrarse dentro de las “Encefalopatías Epilépticas y del Desarrollo”, mostrando fenotipos clínicos en los que existe una interacción entre epilepsia a menudo refractaria con regresión y afectación del neurodesarrollo, en un contexto de síndromes epilépticos más o menos definidos. Las causas genéticas subyacentes hoy en día pueden identificarse con precisión en muchos casos, permitiendo un acercamiento terapéutico precoz e individualizado en un contexto de Medicina de Precisión. Existen múltiples ejemplos pero es particularmente significativo el de la epilepsia ligada a SCN1A, incluyendo el síndrome de Dravet. En muchos casos la mutación específica permite delinear la historia natural futura, por lo que puede ofrecerse una guía anticipatoria exhaustiva que cubre múltiples necesidades del paciente más allá del uso específico de fármacos.(AU)

Rare diseases with epilepsy are a heterogeneous group of entities in which there is frequently a genetic cause. In the majority of cases, the epilepsy that appears in these patients can be classified as “Developmental and Epileptical Encephalopathies”, showing clinical phenotypes in which there is an interaction between often refractory epilepsy with regression and impairment of neurodevelopment, in a context of epileptic syndromes more or less defined. The underlying genetic causes can today be precisely identified in many cases, allowing an early and individualized therapeutic approach in a Precision Medicine context. There are multiple examples, but epilepsy linked to SCN1A is particularly significant, including Dravet syndrome. In many cases, the specific mutation allows the future natural history to be delineated, so comprehensive anticipatory guidance can be offered that covers multiple patient needs beyond the specific use of drugs.(AU)

Desafíos en el empleo de los medicamentos huérfanos

Las enfermedades raras son aquellas que tienen baja prevalencia y que, por lo tanto, el desarrollo de medicamentos para tratarlas no es rentable para las empresas farmacéuticas debido a la baja demanda. A pesar de que ya se cuenta con diferentes políticas públicas alrededor del mundo para incentivar a las industrias farmacéuticas a investigar estos medicamentos, conocidos como medicamentos huérfanos, su desarrollo conlleva muchas dificultades en las evaluaciones clínicas y el precio final para el público es muy elevado. Si bien en años recientes se ha planteado el uso de tecnología de impresión en 3D para producir estos medicamentos o incluso recurrir a otros medicamentos previamente aprobados para tratar enfermedades raras, existe un historial de mal uso de las legislaciones por parte de las empresas con el fin de generar beneficios comerciales, por lo que estas políticas deben reforzarse para que cumplan su propósito; ayudar a una población muy vulnerable. El objetivo del presente texto es exponer los resultados de una revisión documental sobre el panorama científico y sociopolítico en el que se encuentra el problema de las enfermedades raras y los medicamentos huérfanos, así como las posibles soluciones que se están desplegando para abordarlo. Deriva de un estudio que se desarrolla en el momento actual en la Universidad Autónoma Metropolitana, de Ciudad de México.

The strange illnesses are those that have low prevalence and that, therefore, the development of medications to treat them is not profitable for the pharmaceutical companies due to the drop demands. Although it is already counted with different political public around the world to motivate to the pharmaceutical industries to investigate these medications, well-known as orphan medications, their development bears many difficulties in the clinical evaluations and the final price for the public it is very high. Although in recent years he/she has thought about the use of impression technology in 3D to produce these medications or even to appeal to other medications previously approved to treat strange illnesses, a record of wrong use of the legislations exists on the part of the companies with the purpose of generating commercial benefits, for what these politicians should be reinforced so that they complete its purpose; to help a very vulnerable population. The objective of the present text is to expose the results of a documental revision on the scientific and sociopolitical panorama in which is the problem of the strange illnesses and the orphan medications, as well as the possible solutions that they are spreading to approach it. It derives of a study that is developed in the current moment in the Metropolitan Autonomous University, of Mexico City.

Implementación de programas de transición de la adolescencia a la edad adulta / Implementation of programmes for the transition of adolescents to adult care

Hasta un 15-20% de adolescentes tienen algún problema de salud crónico. La adolescencia representa un periodo de riesgo especial para la evolución de las enfermedades crónicas, tanto en aquellos con padecimientos con mayor prevalencia como en los afectados por enfermedades raras. La transición de la asistencia pediátrica a la adulta empieza con la preparación y capacitación del paciente pediátrico, acostumbrado a los cuidados tutelados, para que asuma la responsabilidad de su autocuidado en una unidad de adultos. La transferencia es el momento en el que la persona joven pasa a los servicios de adultos y es dada de alta de los servicios pediátricos. La transición sólo se completa cuando los jóvenes están integrados y funcionan con total competencia dentro del servicio de adultos. Los profesionales de adultos tienen un rol crucial al momento de recibir e integrar a los adultos jóvenes. Un programa de transición puede incluir transiciones de diferente complejidad, desde enfermedades frecuentes y conocidas como el asma, que requieren un proceso más sencillo, hasta enfermedades raras complejas con necesidad de participación de personal muy especializado. La transición requiere un trabajo en equipo con participación de numerosos profesionales: pediatras y médicos de adultos, enfermeras, psicólogos clínicos, trabajadores sociales sanitarios, equipo de Farmacia, y personal administrativo. Es importante implicar a los adolescentes en la toma de decisiones y que los padres los dejen ir progresivamente. Un programa de transición bien estructurado puede mejorar los resultados en salud, la experiencia del paciente y la utilización y coste de los cuidados sanitarios.(AU)

Up to 15%–20% of adolescents have a chronic health problem. Adolescence is a period of particular risk for the development or progression of chronic diseases for both individuals with more prevalent conditions and those affected by rare diseases. The transition from paediatric to adult care begins with preparing and training the paediatric patient, accustomed to supervised care, to assume responsibility for their self-care in an adult care setting. The transition takes place when the young person is transferred to adult care and discharged from paediatric care services. It is only complete when the youth is integrated and functioning competently within the adult care system. Adult care providers play a crucial role in welcoming and integrating young adults. A care transition programme can involve transitions of varying complexity, ranging from those required for common and known diseases such as asthma, whose management is more straightforward, to rare complex disorders requiring highly specialized personnel.(AU)

Tumor glômico em antebraço direito: uma apresentação atípica / Glomus tumor in the right forearm: an atypical presentatio

Introdução: Tumor glômico é uma neoplasia mesenquimal rara que compreende menos de 2% dos tumores de partes moles. Trata-se de um tumor com comportamento clínico benigno, de maior incidência no sexo feminino, entre a segunda e quarta década de vida. Objetivo: Apresentar um caso clínico de tumor glômico. Material e Método: Estudo tipo relato de caso. Relato: Homem de 35 anos de idade com nódulo em antebraço direito há 5 anos. Tratava-se de um nódulo, não ulcerado, eritemato-acastanhado, medindo cerca de 3 milímetros de diâmetro, doloroso a palpação e sensível ao contato com líquidos em baixas temperaturas. Após biópsia incisional da lesão, o exame foi compatível com o aspecto histopatológico de Tumor Glômico, com a presença de vasos sanguíneos dilatados e circundados por pequenas células glômicas com núcleos ovalados, citoplasma eosinofílico e bordas regulares, o que permitiu o correto diagnóstico e o planejamento terapêutico. Até a conclusão do trabalho, o paciente não havia realizado a remoção cirúrgica do tumor, porém não apresentou limitações ou queixas importantes. Conclusão: O estudo do caso do tumor glômico permitirá maior elucidação de novos casos, tendo em vista a raridade do tumor, o quadro clínico pouco específico e escassez de literatura disponível

Introduction: Glomus tumor is a rare mesenchymal neoplasm that comprises less than 2% of soft tissue tumors. It is a tumor with a benign clinical behavior, with a higher incidence in females, between the second and fourth decade of life. Objective: To present a clinical case of glomus tumor. Material and Method: Case report study. Report: 35-year-old man with a nodule on his right forearm for 5 years. It was a non-ulcerated, erythematous-brown nodule, measuring approximately 3 millimeters in diameter, painful on palpation and sensitive to contact with liquids at low temperatures. After incisional biopsy of the lesion, the examination was compatible with the histopathological appearance of Glomus Tumor, with the presence of dilated blood vessels surrounded by small glomus cells with oval nuclei, eosinophilic cytoplasm and regular borders, which allowed the correct diagnosis and planning therapeutic. Until the conclusion of the work, the patient had not undergone surgical removal of the tumor, but did not present any limitations or major complaints. Conclusion: The study of the glomus tumor case will allow greater elucidation of new cases, given the rarity of the tumor, the non-specific clinical picture and the scarcity of available literature

Introducción: El tumor glómico es una neoplasia mesenquimatosa rara que comprende menos del 2% de los tumores de tejidos blandos. Es un tumor de comportamiento clínico benigno, con mayor incidencia en el sexo femenino, entre la segunda y cuarta década de la vida. Objetivo: Presentar un caso clínico de tumor glómico. Material y Método: Estudio de caso clínico. Informe: Hombre de 35 años con nódulo en antebrazo derecho desde hace 5 años. Se trata de un nódulo de color marrón eritematoso, no ulcerado, de aproximadamente 3 milímetros de diámetro, doloroso a la palpación y sensible al contacto con líquidos a bajas temperaturas. Luego de la biopsia incisional de la lesión, el examen fue compatible con el aspecto histopatológico de Tumor Glómico, con presencia de vasos sanguíneos dilatados rodeados de pequeñas células glómicas con núcleos ovalados, citoplasma eosinofílico y bordes regulares, lo que permitió el correcto diagnóstico y planificación terapéutica. Hasta la conclusión del trabajo, el paciente no había sido sometido a extirpación quirúrgica del tumor, pero no presentaba limitaciones ni quejas importantes. Conclusión: El estudio del caso de tumor glómico permitirá un mayor esclarecimiento de nuevos casos, dada la rareza del tumor, el cuadro clínico inespecífico y la escasez de literatura disponible

Implementation of programmes for the transition of adolescents to adult care.

Up to 15-20% of adolescents have a chronic health problem. Adolescence is a period of particular risk for the development or progression of chronic diseases for both individuals with more prevalent conditions and those affected by rare diseases. The transition from paediatric to adult care begins with preparing and training the paediatric patient, accustomed to supervised care, to assume responsibility for their self-care in an adult care setting. The transition takes place when the young person is transferred to adult care and discharged from paediatric care services. It is only complete when the youth is integrated and functioning competently within the adult care system. Adult care providers play a crucial role in welcoming and integrating young adults. A care transition programme can involve transitions of varying complexity, ranging from those required for common and known diseases such as asthma, whose management is more straightforward, to rare complex disorders requiring highly specialized personnel. The transition requires teamwork with the participation of numerous professionals: paediatricians and adult care physicians, nurses, clinical psychologists, health social workers, the pharmacy team and administrative staff. It is essential to involve adolescents in decision-making and for parents to let them take over gradually. A well-structured transition programme can improve health outcomes, patient experience, the use of health care resources and health care costs.

Prevalencia de la Telangiectasia Hemorrágica Hereditaria: estudio de base poblacional en la Comunitat Valenciana (España) / Prevalence of Hereditary Hemorrhagic Telangiectasia: a population-based study in the Valencian region (Spain)

Fundamentos: La Telangiectasia Hemorrágica Hereditaria (THH) es una enfermedad de baja prevalencia, que se presenta con signos y síntomas muy heterogéneos y de la que apenas se dispone de estudios epidemiológicos de base poblacional. Los objetivos de este estudio fueron describir las características sociodemográficas de las personas afectadas por THH en la Comunitat Valenciana (CV), determinar su prevalencia y mortalidad, y analizar las fuentes de captación y pruebas de verificación utilizadas por el Sistema de Información de Enfermedades Raras de la CV (SIER-CV). Métodos: Se realizó un estudio epidemiológico observacional transversal de casos prevalentes de THH durante 2010-2019 en el SIER-CV. Se determinó la distribución de las características sociodemográficas y clínicas, la prevalencia y mortalidad, y se analizaron las fuentes de captación y pruebas de verificación utilizadas por SIER-CV. El análisis estadístico de los datos se realizó mediante el programa Stata (versión 16.1) y Microsoft Excel Office. Resultados: Durante 2010-2019 se identificaron doscientos casos, de los que el 55,5% eran mujeres. Las edades medias fueron: de captación 56,8 años, y de diagnóstico 50,9 años. El 48,4% fueron diagnosticados entre los treinta y seis, y los sesenta y cuatro años. Fallecieron el 25,5%, con 76,6 años de edad media, identificándose diferencias estadísticamente significativas en mayores de sesenta y cuatro años. La prevalencia fue 39,6 por cada millón de habitantes y la tasa cruda de mortalidad de 10,1 por cada millón de habitantes. El 95,5% se captaron por el Conjunto Mínimo Básico de Datos y la prueba de verificación más frecuente fue la base clínica (45,7%). Conclusiones: La tendencia ascendente de la prevalencia coincide con un mejor conocimiento de la THH, que facilita la detección de casos, y también con fallecimientos en edades avanzadas...(AU)

Background: The Hereditary Haemorrhagic Telangiectasia (HHT) is a low prevalence disease which presents heterogeneous signs and symptoms and just few population-based epidemiological studies are available. The aims of this paper were to describe the sociodemographic characteristics of people affected by HHT in the Valencian Region (VR), to determine its prevalence and mortality rate, and to analyse the sources of recruitment and verification tests used by the Rare Diseases Information System of the VR (SIER-CV).Methods: Cross-sectional observational epidemiological study of HHT prevalent cases between 2010-2019 in SIER-CV was performed. The distribution of sociodemographic and clinical characteristics were determined, the prevalence and mortality rates, and the sources of recruitment and verification tests used by SIER-CV were analysed. Statistical analysis was performed usingStata (version 16.1) and Microsoft Excel Office. Results: During 2010-2019, two hundred cases were identified, 55.5% were female. The mean ages were: 56.8 years at recruitment and 50.9 years at diagnosis. 48.4% of cases were diagnosed between thirty-six/sixty-four years of age. 25.5% died, with a mean age of 76.6 years, identifying statistically significant differences above the age of 64. The prevalence was 39.6/1,000,000 inhabitants and the crude mortality rate was 10.1/1,000,000 inhabitants. 95.5% of cases were recruited from the Hospital discharges database and the most frequent verification test was the clinical basis (45.7%). Conclusions: The increasing trend in prevalence coincides with a better knowledge of HHT, which favours its detection, and also with dying at older ages. To describe the situation of HHT in the VR facilitates its health management and contributes to the establishment of the relevant health policies for the HHT...(AU)

Enfermedades sin diagnostico y enfermedades raras: avances en neurodesarrollo / Rare diseases and undiagnosed diseases: advances in neurodevelopment

Resumen Las enfermedades raras y enfermedades sin diag nóstico se han posicionado en los últimos años como condiciones clínicas que han permitido avanzar el en tendimiento de las funciones de los genes y el im pacto en el desarrollo del individuo. En esta revisión, presentamos como los esfuerzos individuales hechos por muchos años para entender la fisiopatología de en fermedades comunes, enfermedades raras y otras aún más raras, como las enfermedades sin diagnóstico, que se unen hoy para, de manera cooperativa, avanzar en el conocimiento científico. Estos avances en el conoci miento permiten aplicar los avances obtenidos en un grupo de condiciones clínicas a otras con características fenotípicas similares o viceversa. El trabajo conjunto de equipos multidisciplinarios y la comunicación entre clínicos e investigadores proporcionarán oportunidades para proveer mejores oportunidades de tratamiento para pacientes y familias a lo largo de múltiples diagnósticos comunes o raros.

Abstract Rare diseases and undiagnosed diseases have re cently positioned themselves as clinical entities that provide important opportunities to advance our under standing of gene functions and the impact of them in the individual development. In this review, we present how efforts made over years to understand common diseases, rare diseases and even undiagnosed diseases come together today to cooperatively advances scientific knowledge. These advance in science and new acquired knowledge, make possible to apply the advances ob tained in a group of clinical conditions to others with similar phenotypic characteristics or vice versa. The cooperative work of multidisciplinary teams and the communication between clinicians and researchers have and will provide opportunities for better treatments for patients and families across multiple common and rare diseases.

Síndrome de Klippel-Trenaunay-Weber. Presentación de un caso y revisión de la literatura

El síndrome de Klippel-Trenaunay-Weber es una malformación vascular congénita poco frecuente. Está caracterizada por una triada de manifestaciones clínicas que comprende una malformación vascular venular, linfática y venosa, junto con hipertrofia esquelética; aumento de tejidos blandos de uno o más miembros; y la presencia de fistulas arteriovenosas. Se presenta el caso de una niña de 5 años de edad, a quien se le confirmó por hallazgos clínicos e imagenológicos un síndrome de Klippel-Trenaunay-Weber. Esta es una enfermedad rara, poco frecuente, con un patrón de herencia genética no bien definido, que necesita de un manejo multidisciplinario. El tratamiento de elección es el clínico sintomático, enfocado a evitar la discapacidad, mejorar la capacidad funcional, calidad de vida y prevenir complicaciones. Se presenta el caso por lo poco frecuente del padecimiento para mostrar su seguimiento y además con fines docentes.

Klippel-Trenaunay-Weber syndrome is a rare congenital vascular malformation. Its characterized by a triad of clinical manifestations that includes venular, lymphatic, and venous vascular malformation, together with skeletal hypertrophy, soft tissue enlargement of one or more limbs, and presence of arteriovenous fistulas. We present the case of a 5-year-old girl who was confirmed by clinical and imaging findings to have Klippel-Trenaunay-Weber syndrome. This is a rare, infrequent disease with a not well-defined genetic inheritance pattern that requires multidisciplinary management. The treatment of choice is the symptomatic clinic, focused on avoiding disability, improving functional capacity, quality of life and preventing complications. The case is presented due to the infrequent nature of this condition to show its follow-up and also for teaching purpose