Síndrome de Progeria Hutchinson-Gilford

El Síndrome de Progeria de Hutchinson- Gilford es una enfermedad que se caracteriza por el envejecimiento prematuro en niños, debido a una mutación en el gen de Lámina tipo A involucrado en la mitosis celular. En el presente trabajo, con el objetivo de dar difusión al conocimiento de esta enfermedad, se señalan los procesos involucrados en su desarrollo, así como los avances científicos y el alcance de nuevas ventanas terapéuticas. La revisión se realizó consultando artículos en español e inglés empleando los motores de búsqueda Pubmed y Google Académico. La actualización del personal de salud sobre las enfermedades genéticas congénitas es de vital importancia para mejorar su detección, atención y manejo.

Hutchinson-Gilford Progeria Syndrome is a disease characterized by premature aging in children, due to a mutation in the Lamina type A, gene involved in cellular mitosis. In the present work, with the aim of spreading the knowledge of this disease, the processes involved in its development, the scientific advances, and the scope of new therapeutic treatments were summarized. The review was carried out by consulting articles in Spanish and English using the Pubmed and Google Academic search engines. The updating of health personnel on congenital genetic diseases is of vital importance to improve their detection, care and management.

A Síndrome de Hutchinson-Gilford Progeria é uma doença caracterizada pelo envelhecimento prematuro em crianças, devido a uma mutação no gene lamina tipo A envolvido na mitose celular. No presente trabalho, como objetivo de divulgar o conhecimento desta doença, são indicados os processos envolvidos no seu desenvolvimento, bem como os avanços científicos e o âmbito de novas janelas terapêuticas. A análise foi realizada através da consulta de artigos em espanhol e inglês utilizando os motores de busca pubmed e Google Scholar. A atualização do pessoal de saúde sobre doenças genéticas congénitas é de importância vital para melhorar a sua deteção, cuidados e gestão.

Efectos patogénicos de los productos finales de glicación avanzada en el proceso de envejecimiento-enfermedad

RESUMEN Los productos finales de glicación avanzada -conocidos como productos de la reacción de Maillard-, formados por glicación directa no enzimática de azúcares reductores con grupos amino libres de proteínas, provocan cambios estructurales y funcionales en las mismas, cuya producción endógena es incrementada con la edad, el estrés oxidativo, así como por factores externos, provocando envejecimiento prematuro y enfermedades degenerativas. El objetivo de la revisión fue obtener una visión actualizada de los avances en investigaciones sobre los efectos de productos finales de glicación avanzada y su interrelación con el estrés oxidativo en el proceso de envejecimiento-enfermedad. En la revisión se consideraron los principales artículos más recientes sobre el tema en las bases de datos PubMed, SciELO, ClinicalKey y LILACS. Se evidencian los efectos patogénicos de los productos finales de glicación avanzada que contribuyen al estrés oxidativo y a la inflamación, de forma especial en el envejecimiento prematuro, diabetes, enfermedad cardiovascular y en otras enfermedades neurodegenerativas, como un aspecto preocupante en el tema del envejecimiento poblacional y su enorme costo para la sociedad futura.

ABSTRACT The advanced glycation end-products-known like products of the Maillard reaction-formed by a direct non-enzymatic glycation of reducing sugars with amino groups free of proteins, cause structural and functional changes in them, whose endogenous production is incremented with age, oxidative stress, as well as by external factors, causing premature aging and degenerative diseases. The objective of the review objective was to obtain an updated view of the advances in research on the effects of the advanced glycation end products and their interrelation with the oxidative stress in the aging-disease process. In the review the authors considered the most recent leading articles on the topic published in the databases PubMed, SciELO, ClinicalKey and LILACS. The pathogenic effects of the advanced glycation end products that contribute to oxidative stress and inflammation are evidenced, especially in premature aging, diabetes, cardiovascular disease and other neurodegenerative diseases, as a worrying aspect in the issue of population aging and its enormous cost for future society.

Advance of clinical and genetic studies on Cockayne syndrome / 中华实用儿科临床杂志

Cockayne syndrome is a rare autosomal recessive disorder with multisystem degenerative disorders caused by DNA repair defect. The patients usually presented with developmental delay,failure to thrive,premature aging,cutaneous photosensitivity and microcephaly. The phenotype was a continuous spectrum,with severity from severe to mild as Cerebro - oculofacio - skeletal syndrome (COFS),Cockayne syndrome type Ⅱ,Cockayne syndrome type Ⅰ, Cockayne syndrome type Ⅲ and ultraviolet ray(UV)- sensitive syndrome. In addition,there is xeroderma pigmentosum -Cockayne syndrome type. Cockayne syndrome manifested as the defect of DNA repair after UV damage cytologically. The main pathogenic genes of Cockayne syndrome are CSA (ERCC8)and CSB (ERCC6). Now,the progress of clinical and genetic studies on Cockayne syndrome were reviewed.

Síndrome de Werner: a propósito de un caso probable / Werner's syndrome, about a probable case

Resumen: el síndrome de Werner es una patología poco frecuente, de herencia autosómica recesiva, caracterizado por signos de envejecimiento prematuro y tendencia a desarrollar tumores malignos. El diagnóstico de esta enfermedad es principalmente clínico, con hallazgos predominantes como talla baja y envejecimiento precoz. En este artículo se presenta el caso de un paciente de 49 años de edad, con signos tempranos de envejecimiento desde los 15 años y ateroesclerosis temprana asociada, que lo lleva a amputación quirúrgica de extremidad inferior derecha. De acuerdo con los criterios diagnósticos del síndrome de Werner este es el primer caso probable en el suroccidente colombiano. (AU)

Abstract: Werner syndrome is a rare, autosomal recessive pathology, characterized by signs of premature aging and tendency to develop malignant tumors. The diagnosis is principally clinical, with predominating findings as short stature and precocious aging. In this article, it's presented the case of a 49-year-old patient with early signs of aging from the age of 15 years and associated early atherosclerosis that leads to the right lower limb surgical amputation. According to the diagnostic criteria of Werner syndrome, this is the first probable case in the Colombian Southwest. (AU)

Functional lung rejuvenation in obese patients after bariatric surgery / Rejuvenescimento pulmonar funcional em pacientes obesos após cirurgia bariátrica

Summary Objective: To determine the lung age (LA) in obese people before and after bariatric surgery, compare the LA with the chronological age (CA) before and after the peration, and verify whether there was a functional pulmonary rejuvenation after it. Methods: A prospective longitudinal study including 43 morbidly obese patients who underwent bariatric surgery. The patients underwent clinical and spirometric evaluation in two stages, before and after the surgery. In both stages, LA, CA and spirometric variables were measured. Results: A significant improvement in the spirometric variables (FVC; FEV1; and FEV1/FVC ratio) was found after the operation (p≤ 0.0001). Comparing the LA before (50.93±13.36 years) and after the surgery (39.02±12.95 years), there was an important reduction of 11.90±9.12 years (95CI:9.10-14.71; p≤0.0001) in LA after surgery. The difference between LA and CA before surgery was 12.20± 11.71 years (95CI:8.60-15.81) with significant difference (p≤0.0001), and the difference between LA and CA after surgery was -1.95±11.83 years (95CI: -5.59-1.69) with no significant difference (p≤0.28). Regarding LA, we observed a pulmonary aging of 12.20±11.71 years before the surgery and a pulmonary rejuvenation of 11.90±9.12 years after it. Conclusion: Morbid obesity is responsible for early damage and functional accelerated pulmonary aging. After the correction of the body weight by surgery, there is a functional pulmonary rejuvenation demonstrated by the normalization of LA in relation to CA.

Resumo Objetivo: determinar a idade pulmonar (IP) em obesos no pré e pós-operatório de cirurgia bariátrica, comparar a IP com a idade cronológica (IC) antes e após a cirurgia, e verificar se houve rejuvenescimento pulmonar funcional após a cirurgia. Métodos: estudo longitudinal, prospectivo, envolvendo 43 pacientes obesos mórbidos submetidos à cirurgia bariátrica. Os pacientes foram submetidos à avaliação clínica e espirométrica antes e após a cirurgia, sendo determinadas IP, IC e variáveis espirométricas. Resultados: observou-se melhora significativa nas variáveis espirométricas (VEF1, CVF e razão VEF1/CVF) após a cirurgia (p≤0,0001). Comparando a IP antes (50,93±13,36 anos) e após a cirurgia (39,02±12,95 anos), observou-se redução significativa da IP no pós-operatório de 11,90±9,12 anos (IC 95% 9,10-14,71; p≤0,0001). A diferença entre IP e IC no pré-operatório foi de 12,20±11,71 anos (IC 95% 8,60-15,81) com diferença significativa (p≤0,0001). A diferença entre IP e IC no pós-operatório foi de -1,95±11,83 anos (IC 95% -5,59-1,69), sem apresentar diferença significativa (p≤0,28). Quando comparamos a IP antes e após a cirurgia, observamos um envelhecimento pulmonar de 12,20±11,71 anos antes e um rejuvenescimento pulmonar de 11,90±9,12 anos após a cirurgia. Conclusão: a obesidade mórbida causa dano precoce e envelhecimento pulmonar funcional acelerado. Após a correção do peso corpóreo pela cirurgia, há um rejuvenescimento pulmonar funcional, mostrado pela normalização da IP em relação à IC.

Progeria:: enfermedad coronaria e insuficiencia cardíaca en paciente joven

La progeria es una enfermedad caracterizada por el envejecimiento prematuro en los primeros años de vida. El diagnóstico es fundamentalmente clínico y la supervivencia más allá de la adolescencia es inusual. En más del 80% de los casos la muerte se debe a complicaciones cardiovasculares. Se presenta el caso clínico de un paciente masculino de 26 años de edad, diagnosticado de progeria, que cursa internación por infarto agudo de miocardio ínfero-latero-dorsal con compromiso eléctrico y hemodinámico del ventrículo derecho. En resumen, los pacientes con progeria suelen presentarse con enfermedad coronaria a edades tempranas. Los registros de estos grupos de pacientes informan que la gran mayoría fallecen durante la adolescencia a causa de enfermedad coronaria. Mostramos un caso de un paciente joven con enfermedad coronaria severa que debuta con un infarto agudo de miocardio con resolución favorable.

Progeria: coronary artery disease and heart failure in a young patient Progeria is a disease characterized by premature aging in the first years of life. The diagnosis is essentially clinical and survival beyond adolescence is unusual. In over 80% of cases death due to cardiovascular complications. The case report of a male patient of 26 years old, diagnosed with progeria, coursing hospitalization for acute inferio-latero-dorsal myocardial infarction with electric and hemodynamic right ventricular involvement is presented. In summary, patients with progeria usually appear with coronary disease at early ages. The records of these groups of patients report that the vast majority die during adolescence due to coronary disease. We report a case of a young patient with severe coronary artery disease who presents with an acute myocardial infarction with favorable resolution.

Progeria: doença arterial coronariana e insuficiência cardíaca em um paciente jovem Progeria é uma doença caracterizada pelo envelhecimento prematuro nos primeiros anos de vida. O diagnóstico é essencialmente clínico e sobrevivência além da adolescência é incomum. Em mais de 80% dos casos de morte devido a complicações cardiovasculares. É apresentado um caso clínico de um paciente do sexo masculino de 26 anos, diagnosticado com progeria, correndo hospitalização por infarto agudo do miocárdico ínfero-látero-dorsal com comprometimento elétrico e hemodinâmico do ventrículo direito. Em resumo, os pacientes com progeria geralmente aparecem com doença coronariana em idades precoces. Os registros desses grupos de pacientes relatam que a grande maioria morre durante a adolescência devido a doença coronária. Relatamos o caso de um jovem paciente com doença arterial coronariana grave, que debuta com um infarto agudo do miocárdio com resolução favorável.

Autophagy activity is inhibited in human fibroblast cells stably overexpressing H-RasV12 / 第二军医大学学报

Objective: To investigate the relationship between oncogenic H-RasV12 overexpression/activation and the autophagic activity by observing the effect of Ras overexpression on autophagic activity in human fibroblast cells. Methods: Human BJ fibroblast cells were transfected with H-RasV12 or control vector, and then the cellular responses to H-RasV12 overexpression were analyzed by observing the morphology, cell growth curve, senescence-associated β-Gal staining, Western blotting analysis, flow cytometry, and suppression of autophagy-related protein 5 (ATG5) by siRNA. Results: Compared with control group, BJ cells overexpressing H-RasV12 developed prominent premature senescence and inhibited autophagic activity, as manifested by significant accumulation of p62 and light chain 3 II (LC3 II). The autophagy inhibition by H-RasV12 remained stable during the study period; the apoptosis rate was increased in H-RasV12overexpressing BJ cells compared with that in the control cells. Suppression of ATG5 by siRNA led to more severe senescence in Ras-overexpressing BJ cells. Conclusion: Our results suggest that the autophagy activity is inhibited in human fibroblast cells stably overexpressing oncogenic H-RasV12, and the inhibition is in the later stage of autophagy, which may be related to H-RasV12-related tumorigenesis.

Síndrome de Cockayne: informe de dos casos clínicos y revisión de la literatura / Cockayne syndrome: report of two clinical cases and review of the literature

Introducción: el síndrome de Cockayne es un trastorno genético autosómico recesivo, caracterizado por detención del crecimiento, retraso del desarrollo, envejecimiento prematuro y fotosensibilidad. La prevalencia es de 1/100.000 nacidos vivos; es más frecuente en el sexo masculino con una relación 3:1. Desde el punto de vista genético se han descrito dos grupos: A: mutación del gen CSA (CKN1, ERCC8) en el cromosoma 5q12; B: mutación del gen CSB (ERCC6) en el cromosoma 10q11. Presentamos dos casos diagnosticados sobre bases clínicas pero en los que carecemos de estudios genéticos. Caso 1. Niña escolar producto de padres consanguíneos quien desde el nacimiento presenta hipotonía e hipomotilidad, retardo global del desarrollo, déficit pondoestatural, cara envejecida, rasgos dismórficos, fotosensibilidad, espasticidad e hipoacusia neurosensorial y hallazgos tomográficos característicos del síndrome. Actualmente está en rehabilitación. Caso 2. Adolescente de sexo femenino con crisis convulsivas desde los dos meses, poco progreso en el desarrollo psicomotor y pondoestatural, rasgos dismórficos y cara envejecida, hipoacusia neurosensorial bilateral, distonías repetitivas; en varias oportunidades sufrió procesos infecciosos respiratorios uno de los cuales, con neumonía bilateral, la llevó a la muerte a los 14 años. Conclusión: se presentan estos casos y se revisa la literatura para llamar la atención sobre este síndrome de modo que se lo sospeche tempranamente en pacientes con retardo del desarrollo psicomotor, envejecimiento prematuro y fotosensibilidad. El diagnóstico temprano es la base para brindar consejería genética a los padres.

Introduction: Cockayne syndrome is an autosomal, recessive genetic disorder, characterized by poor growth, development impairment, premature aging, and photosensitivity. Prevalence is 1/100.000 live births, and it is more frequent in males with a ratio of 3:1. From the genetic point of view two groups have been described: Group A: mutation of the CSA gene (CKN1, ERCC8) on chromosome 5q12. Group B: mutation of the CBS gene (ERCC6) on chromosome 10q11. We report two cases that were diagnosed solely on clinical bases because no genetic studies were available. Case 1. A school-girl, born from consanguineous parents. Since birth she has suffered from hypotonia and hypomotility. She has development delay, low weight and height gain, aged face, dysmorphic features, photosensitivity, spasticity, sensorineural hearing loss, and typical findings in the CT scan. She is currently on rehabilitation. Case 2. A female teenager with seizures from the age of two months; she made slow progress in psychomotor development, and had low weight and height gain. Her features were dysmorphic and her face aged. She had bilateral sensorineural hearing loss, and repeated dystonias. She suffered from repeated respiratory infections and died, aged 14, from respiratory failure secondary to bilateral pneumonia. Conclusion: We report these two cases and a review of the literature in order to attract attention to Cockayne syndrome so that early diagnoses can be made in children with psychomotor development delay, premature aging and photosensitivity. Early diagnoses are the basis for genetic counseling.

Ocular manifestations in the Hutchinson-Gilford progeria syndrome.

The Hutchinson-Gilford progeria (HGP) syndrome is an extremely rare genetic condition characterized by an appearance of accelerated aging in children. The word progeria is derived from the Greek word progeros meaning ‘prematurely old’. It is caused by de novo dominant mutation in the LMNA gene (gene map locus 1q21.2) and characterized by growth retardation and accelerated degenerative changes of the skin, musculoskeletal and cardiovascular systems. The most common ocular manifestations are prominent eyes, loss of eyebrows and eyelashes, and lagophthalmos. In the present case some additional ocular features such as horizontal narrowing of palpebral fissure, superior sulcus deformity, upper lid retraction, upper lid lag in down gaze, poor pupillary dilatation, were noted. In this case report, a 15-year-old Indian boy with some additional ocular manifestations of the HGP syndrome is described.

Hutchinson-Gilford progeria syndrome.

Progeria is a rare genetic disorder characterized by premature aging, involving the skin, bones, heart, and blood vessels. We report a 4-year-old boy who presented with clinical manifestations of progeria. He had characteristic facies, prominent eyes, scalp and leg veins, senile look, loss of scalp hair, eyebrows and eyelashes, stunted growth, and sclerodermatous changes. The present case is reported due to its rarity.