Avaliação funcional em indivíduos com doença de Huntington: uma série de casos / Functional evaluation in Huntington's disease: a series of cases

A doença de Huntington (DH) é uma desordem neurodegenerativa, que cursa com distúrbios motores, cognitivos e comportamentais que contribuem para o comprometimento da funcionalidade. Este estudo investigou o grau de funcionalidade e acometimento de indivíduos portadores da DH, com o Índice de Barthel Modificado (IBM) e por meio do Disease Burden Score (DBS). As variáveis analisadas de cada indivíduo foram: a idade atual, o gênero, a idade de início da doença e o número das repetições CAG (gene HTT). Seis indivíduos foram avaliados, três do sexo masculino 63,6 anos (±10,9) e três do sexo feminino 58,3 anos (±14,2) com o diagnóstico genético positivo para DH provenientes do município de Ervália/MG. O sexo feminino apresentou a idade de início menor comparado ao sexo masculino, com média de 38,3 anos (±8,9) e 46,6 anos (±7,6), respectivamente. O valor médio do número de repetições CAG no sexo feminino foi de 46,3 (±4,1) e no sexo masculino, 42,33 (±1,5). O grau de desempenho funcional determinado pelo IBM foi de 9,3 (±1,1) para o sexo feminino, com dependência total, e para o sexo masculino, 36 (±4,3), com dependência severa. O valor médio obtido pelo DBS no sexo feminino foi de 596,8 (±101,9), com maior grau de acometimento da doença comparado ao sexo masculino com 425,1 (±39,2). O grupo de mulheres com DH apresentou início dos sintomas mais cedo com maior número de expansões CAG quando comparado ao grupo masculino. Todos os pacientes apresentaram dependência total em relação à execução das atividades de vida diária. Sugere-se que pesquisas futuras sejam realizadas com maior número de indivíduos afetados pela DH para que os resultados observados sejam confirmados.

Huntington's disease (HD) is a neurodegenerative disorder, presenting with motor, cognitive and behavioral impairments that contribute to the decrease of the functional performance. This study investigated the degree of functionality and impairment of individuals with HD using the Modified Barthel Index (MBI) and the Disease Burden Score (DBS). The following variables were investigated : the age of onset, the gender, the current age and the number of CAG (HTT gene) repeats. Six HD patients from the municipality of Ervália-MG, three males 63.6 years old (±10.9) and three females 58.3 years old (±14.2), who had a positive genetic diagnosis for HD, were investigated. The female group had the lowest age of onset with an average of 38.3 years (±8.9), compared to the male group, with 46.6 years (±7.6). The mean of the number of CAG repeats in the female gender was 46.3 (±4.1) and in the male, 42.33 (±1.5). The degree of functional performance assessed by IBM was 9.3 (±1.1) for the female group, with total dependence, and for the male group, 36 (±4.3), with severe dependence. The mean of DBS value in the female group was 596.8 (±101.9) with a higher degree of disease involvement compared to the male group 425.1 (±39.2). The group of women with HD showed earlier onset of symptoms with a greater number of CAG repeats when compared to the male group. All patients presented total dependence on daily living activities. We strongly suggest further research involving a larger group of individuals affected by HD for statistical validation.

Evaluating the current state of the art of Huntington disease research: a scientometric analysis

Huntington disease (HD) is an incurable neurodegenerative disorder caused by a dominant mutation on the 4th chromosome. We aim to present a scientometric analysis of the extant scientific undertakings devoted to better understanding HD. Therefore, a quantitative study was performed to examine the current state-of-the-art approaches that foster researchers' understandings of the current knowledge, research trends, and research gaps regarding this disorder. We performed literature searches of articles that were published up to September 2016 in the "ISI Web of Science™" (http://apps.webofknowledge.com/). The keyword used was "Huntington disease". Of the initial 14,036 articles that were obtained, 7732 were eligible for inclusion in the study according to their relevance. Data were classified according to language, country of publication, year, and area of concentration. The country leader regarding the number of studies published on HD is the United States, accounting for nearly 30% of all publications, followed by England and Germany, who have published 10 and 7% of all publications, respectively. Regarding the language in which the articles were written, 98% of publications were in English. The first publication to be found on HD was published in 1974. A surge of publications on HD can be seen from 1996 onward. In relation to the various knowledge areas that emerged, most publications were in the fields of neuroscience and neurology, likely because HD is a neurodegenerative disorder. Publications written in areas such as psychiatry, genetics, and molecular biology also predominated.

Alteraciones neurofisiológicas producidas por la enfermedad de Huntington sobre la calidad de vida / Neurophysiological changes caused by Huntington’s disease on quality of life

La Enfermedad de Huntington (EH), ha sido reconocida como una de las tres enfermedades neurodegenerativas de mayor impacto a nivel mundial, junto al Parkinson y al Alzheimer. El daño producido porla EH afecta principalmente zonas del Sistema Nervioso Central (SNC), como los ganglios basales y tiene una base genética, que es transmitida de generación en generación de manera autosómica dominante. El problema genético específico se localiza en un defecto del brazo corto del cromosoma 4, llamado IT15, que tiene repeticiones trinucleicas superiores a 38 duplicaciones. La EH puede manifestarse en etapa juvenil o en etapa adulta. El diagnóstico de la EH ha resultado en la mayoría de los casos tardío y aúnno se ha descubierto un método eficaz para tratar la enfermedad. La Calidad de Vida (CV) de los pacientes con EH tiende a degradarse a medida que evoluciona la enfermedad, y aún faltan más estudios clínicos interdisciplinarios que la traten con eficacia.

Huntington’s Disease (HD) has been recognized as one of the three neurodegenerative diseases with greatest impact around the world, beside Parkinson’s disease and Alzheimer disease. The damage caused by HD primarily affects areas of the Central Nervous System (CNS), such as the basal ganglia and it a genetic basis, which is transmitted from generation to generation in an autosomal dominant manner. The specific genetic problem is located on the short arm of chromosome 4, called IT15, which has tri-nucleic repetitions above 38 duplications. HD can occur in youth or adulthood stage. The diagnosis of HD has resulted in many delayed cases and there has not yet been found an effective method of treating disease. The Quality of Life (QoL) of patients with HD tends to degrade as the disease progresses and there are still more interdisciplinary clinical studies to be treated effectively.

Cuidados paliativos en la enfermedad de Huntington: perspectivas desde la atención primaria de salud / Palliative care in Huntingtonïs disease: perspective from primary health care

La enfermedad de Huntington (EH) es una enfermedad neurodegenerativa devastadora, hereditaria, caracterizadapor s¡ntomas progresivos motores, cognitivos y psiquitricos, los cuales aparecen mayormente durante la vida adulta. Su curso cl¡nico produce consecuencias físicas, emocionales, cognitivas, sociales y económicas gravesen el paciente y cuidadores. Su prevalencia a nivel mundial se estima en 7-10 por 100000 habitantes pero, en lazona del Valle de Ca¤ete en nuestro pa¡s, se estableció en m s de 40 por 100,000. Actualmente no existe curapara la EH; sin embargo, se dan opciones terapéuticas para el alivio de s¡ntomas con el fin de mejorar la calidadde vida del paciente. Es en este rubro donde radica la importancia de los Cuidados Paliativos, definidos por laOrganización Mundial de la Salud como un enfoque de atención que, mediante medidas de prevenci¢n y alivio delsufrimiento, asiste eficazmente a las personas enfermas y a sus familiares en el afronte de problemas asociados con enfermedades mortales. A pesar del impacto que genera esta patolog¡a en nuestra población, nuestro pa¡s carece de recursos suficientes para el tratamiento integral de los pacientes. Mejorar la atención al final de la vida es un reto moderno que requiere incrementar la formación de los profesionales de la salud y la comunidad, mayor financiaci¢n para la atención y desarrollo de pol¡ticas pertinentes.

Huntington’s disease (HD) is a devastating neurodegenerative disease, hereditary in nature, characterized byprogressive motor, cognitive, and psychiatric symptoms which appear mainly in adulthood and result in seriousphysical, emotional, cognitive, social, and economic consequences in patients and caregivers. Its global prevalenceis estimated in 7-10 per 100000 population, but in the Ca¤ete Valley of Per£, it has reached up to 40 per 100,000 inhabitants. The cure for HD is not yet available but there are many treatment options for symptomatic relief aimed at improving the patient’s quality of life. It is in this context that palliative care measures emerge as a relevantalternative; defined by the World Health Organization as a set of care approaches that, through preventive andsuffering attenuation, assist efficaciously both, patients and their relatives, in facing the problems associated with life-threatening diseases. Despite the importance of involving the population in the research of this disease, our country lacks adequate resources for treatment and patient support. Improving end of life care is a modern challenge that requires increasing the training of health and community professionals, increased funding for the care and development of relevant policies.

Swallowing endoscopy findings in Huntington's disease: a case report

ABSTRACT Huntington's disease (HD) is a degenerative genetic disorder with autosomal-dominant transmission. The triad of symptoms of this disease consists of psychiatric disorders, jerky movements, and dementia. Oropharyngeal dysphagia, which is more evident with disease progression, is also present. Few studies have addressed the swallowing characteristics using objective analysis in this population. The purpose of this research was to describe the swallowing endoscopic findings of the pharyngeal phase in HD. This is a cross-sectional study addressing a clinical case which included two individuals of the same family, male, 32 and 63 years old, designated as individual A and individual B, with progression of the disease for five and 13 years, respectively. Consistent liquid, nectar, and puree were offered during the evaluation. There was presence of posterior oral spillage in liquid and nectar, small amount of pharyngeal residues, and no laryngeal penetration or aspiration in the individuals with HD in this study.

Mid- and long-term anxiety levels associated with presymptomatic testing of Huntington's Disease, Machado-Joseph Disease, Machado-Joseph disease, and familial amyloid polyneuropathy

Objective: To study anxiety as a variable of the mid- and long-term psychological impact of pre-symptomatic testing for three autosomal dominant late-onset disorders – Huntington’s disease (HD), Machado-Joseph disease (MJD) and familial amyloid polyneuropathy (FAP) TTR V30M – in a Portuguese sample. Methods: This cross-sectional study included 203 participants: 170 (83.7%) underwent pre-symptomatic testing for FAP, 29 (14.3%) for HD, and 4 (2%) for MJD. Of the 203 participants, 73 (36.0%) were asymptomatic carriers, 29 (14.5%) were symptomatic carriers, 9 (4.5%) were diagnosed with FAP and had a liver transplant, and 89 (44.5%) were non-carriers. Most were women (58.1%) and married (66.5%). The anxiety variable was assessed using the Zung Self-Rating Anxiety Scale (SAS). Results: The anxiety scores were higher for symptomatic carriers and for those who underwent psychological support consultations over the years. For symptomatic carriers, the mean scores were superior to 40 points, which reflects clinical anxiety. Conclusion: Although it was not possible to differentiate between the mid- and long-term psychological impacts, this study supports the conclusion that the proximity to the age of symptoms onset might be a trigger for anxiety.

Retraso en el diagnóstico de un cuadro grave de enfermedad de Huntington juvenil: un reporte de caso / Delayed diagnosis of juvenile Huntington's diseases: case report

La enfermedad de Huntington es una enfermedad neurodegenerativa que se manifiesta con alteraciones motoras descritas típicamente como movimientos coreiformes, cambios en el estado de ánimo y pérdida de funciones cognitivas. El patrón de herencia de esta enfermedad es autosómico dominante. La alteración genética comprende una expansión inestable del triplete citosina, adenina, guanina en el gen que codifica la proteína huntingtina. La prueba molecular confirma el diagnóstico. El consejo genético debe ser prudente debido al alto riesgo de suicidio. Se presenta el caso de un joven de 14 años con una pobre red de apoyo y un cuadro clínico grave de esta enfermedad en el contexto de un patrón de herencia poco claro.

Huntington's disease is a neurodegenerative disease that is clinically manifested as mood and personality changes, loss of cognitive functions and choreiform movements. The pattern of inheritance is autosomic dominant. It is due to the gradual expansion of a cytosine, adenine, guanine trinucleotide in a gene that codifies the protein Huntington. The molecular diagnosis must be performed to confirm the diagnosis. Genetic counseling must be carefully done due to the high suicide risk among these patients. We present the case of a fourteen-year-old male with a severe disease, poor social support and an unclear pattern of inheritance.

Clinical and genetic analysis of 29 Brazilian patients with Huntington's disease-like phenotype / Análise clínica e genética em 29 pacientes Brasileiros com fenótipo doença de Huntington-símile

Huntington's disease (HD) is a neurodegenerative disorder characterized by chorea, behavioral disturbances and dementia, caused by a pathological expansion of the CAG trinucleotide in the HTT gene. Several patients have been recognized with the typical HD phenotype without the expected mutation. The objective of this study was to assess the occurrence of diseases such as Huntington's disease-like 2 (HDL2), spinocerebellar ataxia (SCA) 1, SCA2, SCA3, SCA7, dentatorubral-pallidoluysian atrophy (DRPLA) and chorea-acanthocytosis (ChAc) among 29 Brazilian patients with a HD-like phenotype. In the group analyzed, we found 3 patients with HDL2 and 2 patients with ChAc. The diagnosis was not reached in 79.3 percent of the patients. HDL2 was the main cause of the HD-like phenotype in the group analyzed, and is attributable to the African ancestry of this population. However, the etiology of the disease remains undetermined in the majority of the HD negative patients with HD-like phenotype.

A doença de Huntington (DH) é uma doença neurodegenerativa caracterizada por coréia, alterações comportamentais e demência, causada por uma expansão patológica do trinucleotídeo CAG no gene HTT. Vários pacientes têm sido descritos com o fenótipo típico para a DH porém sem a mutação esperada. O objetivo deste estudo foi avaliar a ocorrência de doenças como doença de Huntington-símile 2 (DHS-2), ataxias espinocerebelares tipo 1, 2, 3 e 17, atrofia dentatorubral-palidoluisiana e coreo-acantocitose (CAc) entre 29 pacientes brasileiros com fenótipo doença de Huntington-símile. No grupo analisado, encontramos 3 pacientes com DHS-2 e 2 pacientes com CAc. O diagnóstico permaneceu obscuro em 79,3 por cento dos pacientes. DHS-2 foi a principal causa do fenótipo DH-símile no grupo analisado, provavelmente devido a ancestralidade africana na população brasileira. Entretanto, a etiologia permaneceu indeterminada na maioria dos pacientes avaliados.

Sydenham's chorea in a family with Huntington's disease: case report and review of the literature / Coreia de Sydenham numa família com doença de Huntington: relato de caso e revisão da literatura

CONTEXT: Sydenham's chorea affects almost 30 percent of patients with acute rheumatic fever. It is more frequent in females and is rare in the first decade of life, and genetic vulnerability underlies it. Because of easy access to antibiotics, it is now rare in so-called developed countries. CASE REPORT: A 6-year-old boy with a family history of Huntington's disease, who was the only child of an unscreened and asymptomatic mother, was brought for a consultation because of migratory arthralgia, depressed mood, and rapid, abrupt and unintentional movements of his right arm and leg, that had evolved over a three-week period. On physical examination, he presented a grade III/VI systolic heart murmur and right-side choreic movements, giving rise to a deficit of active mobilization. Laboratory tests revealed elevated erythrocyte sedimentation rate (63 mm/h), C-reactive protein (25 mg/l) and antistreptolysin O titer (1,824 U/ml). Cardiovascular evaluation showed mild aortic insufficiency, moderate mitral insufficiency and a prolonged PR interval. A clinical diagnosis of Sydenham's chorea/acute rheumatic fever was made, and therapy consisting of penicillin, haloperidol, captopril and furosemide was instituted, with excellent results. CONCLUSION: In developed countries, Sydenham's chorea seems forgotten and, because of this, little is known about its clinical course and controversy surrounds the therapeutic options available. This occurrence of rheumatic chorea in a family with Huntington's disease highlights the importance of the differential diagnosis for the different forms of chorea.

CONTEXTO: A coreia de Sydenham surge em cerca de 30 por cento dos casos de febre reumática aguda. É mais frequente no sexo feminino, é rara na primeira década de vida e tem por base uma vulnerabilidade genética. Devido ao fácil acesso aos antibióticos, é uma doença rara atualmente nos países ditos desenvolvidos. RELATO DO CASO: Criança de seis anos, sexo masculino, com história familiar de coreia de Huntington, único filho de mãe assintomática e não rastreada, foi trazido à consulta por artralgias migratórias, humor deprimido e movimentos rápidos, abruptos e não intencionais dos membros superior e inferior direitos, com três semanas de evolução. Ao exame físico, apresentava um sopro cardíaco sistólico grau III/VI, e foram presenciados movimentos coreicos à direita, condicionando um défice de mobilização activa. Os exames laboratoriais mostraram aumento da velocidade de sedimentação (63 mm/h), proteína C-reativa (25 mg/L) e título de antiestreptolisina O (1.824 U/mL). O exame cardiovascular revelou insuficiência aórtica ligeira e insuficiência mitral moderada e aumento do intervalo PR. Foi feito o diagnóstico de coreia de Sydenham/febre reumática aguda, tendo sido instituída terapêutica com penicilina, haloperidol, captopril e furosemida, com excelente resultado. CONCLUSÃO: Nos países desenvolvidos, a coreia de Sydenham parece esquecida e, por isso, pouco se sabe quanto ao seu curso clínico e as opções terapêuticas disponíveis são controversas. A ocorrência de um caso de coreia reumática numa família com doença de Huntington realça a importância do diagnóstico diferencial das diferentes formas de coreia.

Doença de Huntington: aspectos diagnósticos e implicações éticas / Huntington's disease: diagnostic aspects and ethical implications

Doença de Huntington é uma afecção neurodegenerativa de herança autosssômica dominante, caracterizada por manifestações neurológicas, neuropsiquiátricas e disfunções autonômicas. Não há tratamento para a doença, fato que levanta questões éticas importantes diante do impacto da confirmação diagnóstica e da possibilidade de um planejamento familiar. Paciente feminina, 68 anos, há três anos com movimentos coreicos de lábios, língua, mãos e pé esquerdo, disfagia, sintomas depressivos e comprometimento de funções cognitivas de média gravidade. A ressonância magnética de crânio apresentou alterações compatíveis com doença de Huntington. Foi realizada avaliação genética, após aconselhamento da pacientes e do familiar responsável, e confirmou-se a hipóstese aventada. O diagnóstico deve ser feito o mais breve possível a fim de diminuir o impacto na vida do portador e de sua família e permitir um planejamento familiar. São muitas dificuldades em lidar com a confirmação do diagnóstico, principalmente quando a autonomia do paciente está comprometida, portanto é fundamental esclarecimento e aconselhamento antes e após o teste.

Vitreitis and movement disorder associated with neurosyphilis and human immunodeficiency virus (HIV) infection: case report / Vitreíte e distúrbio motor associados à neurosífilis e infecção pelo vírus da imunodeficiência humana (HIV): relato de caso

In this report, we describe an unusual patient with a choreiform movement disorder, misdiagnosed as Huntington disease, who later developed dense vitreitis leading to the identification of Treponema pallidum as the underlying pathogen of both abnormalities.

Neste relato descrevemos um caso infreqüente de um paciente com quadro de distúrbio motor coreiforme diagnosticado equivocadamente como doença de Huntington, o qual posteriormente desenvolveu quadro de intensa vitreíte, possibilitando a identificação do Treponema pallidum como o patógeno causador de ambas anormalidades.

Diagnóstico molecular de la enfermedad de Huntington / Molecular diagnosis in Huntington's disease

La enfermedad de Huntington es un padecimiento neurológico degenerativo, de herencia autosómica dominante, causado por una expansión CAG que codifica una secuencia de poliglutamina en la proteína huntingtina. Su frecuencia varía de cinco a 10 afectados por 100 mil individuos en población caucásica. Clínicamente muestra manifestaciones motoras, cognoscitivas, psicológicas y muerte en 10 a 15 años. Avances concretos se han logrado en el conocimiento del mecanismo mutacional, alteraciones del producto proteico y su efecto neuropatológico. Un conjunto de procedimientos como PCR con o sin modificación del ADN, Southern blot y métodos mixtos son analizados en sus características y eficiencia para el diagnóstico molecular de esta enfermedad.

Huntington's disease (HD) is a neurological degenerative disorder, inherited by an autosomal dominant mode, and caused by a CAG triplet expansion coding for a poly-glutamine sequence in the huntingtin protein. HD affects 5-10 in 100,000 individuals from Caucasian population. Clinically patients display motor, cognitive and psychological impairment, and death within 10-15 years. Concrete advances have been achieved in the knowledge of the mutational mechanism, alteration of the protein product and their neuropathological effects. A number of tests such as PCR with or without DNA modification, Southern blot and mixed methods are analyzed. We describe their characteristics and effectiveness for the molecular diagnosis of HD.

Non-choreic movement disorders as initial manifestations of Huntington's disease

We describe seven patients with genetically confirmed Huntington's disease (HD) who had non-choreic movement disorders as presenting symptoms or signs. Patients with movement disorders other than chorea in the early stages tended to have larger CAG trinucleotide repeat expansion in comparison with more "typical" HD patients.

Nós descrevemos sete pacientes com doença de Huntington, geneticamente confirmada, cuja apresentação motora inicial foi diferente de coréia. Pacientes com manifestação motora inicial diferente de coréia apresentaram maior número de expansões repetidas de CAG trinucleotídeo quando comparados com aqueles com sintomatologia motora "típica".

Ethics Issues about Huntington disease

Recent advances in genomic research have led to the development of new diagnostic tools, including tests which make it possible-to predict the future occurrence of monogenetic diseases such as Huntington Disease. Direct mutation analysis for Huntington disease [HD] became possible in 1993. The use of such tests raises a number of ethical, legal and social issues which are usually discussed in the field of patient's rights and medical ethics. However, in the context of predictive genetic tests a key question arises which lies beyond the concept of rights, namely, what should we want to know about our future or what is the best condition to know about our health future? According the classic medicine, it has become accepted that respecting the autonomy of patients justifies their right to know but however recently, commentators have asked whether such respect also justifies patient's right not to know; that is, their right to remain in ignorance. In the field of using genetic test for predetection of Huntington disease some main ethical issues are consent and privacy, reproductive decisions in HD mutation carriers after predictive testing for HD and to identify factors that play a role in decision-making, problems associated with suicidal ideation and suicide in HD, minimizing harm of predictive molecular testing for HD patients, health insurance discrimination of HD patients and also whether people have a duty to pass on the positive results of their genetic tests about HD to relatives who are at risk from the same disease, and, should they refuse, whether physicians and genetic counselors have the duty to do so

Perspectives towards predictive testing in Huntington disease.

OBJECTIVE: Genetic counseling for individuals undergoing presymptomatic testing is lacking in India although testing is easily available. This has an impact on family members of Huntington's disease (HD), an autosomal dominant disease, wherein the age at onset of symptoms varies. AIM: We examine if attitudes differ towards presymptomatic testing for HD amongst HD family members, physicians and laypersons. MATERIALS AND METHODS: A modified questionnaire enquiring about opinions on various personal, family, social and future health care with regards to presymptomatic testing of HD was designed. A physician explained briefly about HD and presymptomatic testing of HD and recorded responses of unaffected family members of HD (n=25) and laypersons (n=50). Medical doctors (n=50) answered the questionnaire based on their knowledge of HD. RESULTS: HD family members, Medical doctors and laypersons were similar in their opinion to undergo the testing. Majority (60%) of HD family members did not wish to communicate test results with their friends when compared to the other two groups. Medical doctors and HD family members were more concerned about certainty of developing disease when the test results are positive. Majority (80%) of Medical doctors and less than half in the other groups felt that their decision to have a child would strongly depend on test results. Large proportion (80%) of HD family members did not wish to report their test results to their employers. CONCLUSIONS: Individuals with knowledge about HD and the test differ in their decision of sharing test results and reproductive choices.

Enfermedad de Huntington: reporte de dos casos en una familia hondureña y revisión de la literatura / Huntingtons diseases: repot of two cases an honduran family review of the literature

La enfermedad de Huntington (EH) es un trastorno genético caracterizado por movimientos anormales, demencia y trastornos neuro-conductuales, con una herencia autosómica dominante. Su etiología es debida a una expansión de tripletes repetidos CAG en el gen HD localizado en el cromosoma 4p16.3, causando 36-121 repeticiones. Describimos a dos pacientes hondureños, miembros de una misma familia, con diagnóstico molecular de EH. El paciente índice se presentó con dificultad para de ambular, disartria, blefaroespasmo y movimientos involuntarios de manos, brazos y pies. Adicionalmente, pérdida de memoria,dificultad para la comprensión de tareas complejas, dificultad para realizar tareas de la vida diaria y pérdida de peso. Asimismo, se discuten las características neuropsiquiátricas de la enfermedad y asuntos éticos de importancia...