RESUMEN
BACKGROUND: Mitochondrial progressive external ophthalmoplegia (PEO) encompasses a broad spectrum of clinical and genetic disorders. We describe the phenotypic subtypes of PEO and its correlation with molecular defects and propose a diagnostic algorithm. METHODS: Retrospective analysis of the clinical, pathological and genetic features of 89 cases. RESULTS: Three main phenotypes were found: 'pure PEO' (42%), consisting of isolated palpebral ptosis with ophthalmoparesis; Kearns-Sayre syndrome (10%); and 'PEO plus', which associates extraocular symptoms, distinguishing the following subtypes: : myopathic (33%), bulbar (12%) and others (3%). Muscle biopsy was the most accurate test, showing mitochondrial changes in 95%. Genetic diagnosis was achieved in 96% of the patients. Single large-scale mitochondrial DNA (mtDNA) deletion was the most frequent finding (63%), followed by multiple mtDNA deletions (26%) due to mutations in TWNK (n=8), POLG (n=7), TK2 (n=6) or RRM2B (n=2) genes, and point mtDNA mutations (7%). Three new likely pathogenic mutations were identified in the TWNK and MT-TN genes. CONCLUSIONS: Phenotype-genotype correlations cannot be brought in mitochondrial PEO. Muscle biopsy should be the first step in the diagnostic flow of PEO when mitochondrial aetiology is suspected since it also enables the study of mtDNA rearrangements. If no mtDNA deletions are identified, whole mtDNA sequencing should be performed.
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Proteínas de Ciclo Celular/genética , ADN Helicasas/genética , ADN Polimerasa gamma/genética , Mitocondrias/genética , Proteínas Mitocondriales/genética , Oftalmoplejía Externa Progresiva Crónica/genética , Ribonucleótido Reductasas/genética , Adolescente , Biopsia , Niño , Preescolar , ADN Mitocondrial/genética , Femenino , Humanos , Lactante , Recién Nacido , Síndrome de Kearns-Sayre/genética , Síndrome de Kearns-Sayre/patología , Masculino , Mitocondrias/patología , Enfermedades Mitocondriales/genética , Enfermedades Mitocondriales/patología , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Oftalmoplejía Externa Progresiva Crónica/patología , Fenotipo , Mutación Puntual/genética , Timidina QuinasaRESUMEN
Lysosomal α-galactosidase A (α-Gal) is the enzyme deficient in Fabry disease (FD), an X-linked glycosphingolipidosis caused by pathogenic mutations affecting the GLA gene. The early-onset, multi-systemic FD classical phenotype is associated with absent or severe enzyme deficiency, as measured by in vitro assays, but patients with higher levels of residual α-Gal activity may have later-onset, more organ-restricted clinical presentations. A change in the codon 118 of the wild-type α-Gal sequence, replacing basic arginine by a potentially sulfhydryl-binding cysteine residue - GLA p.(Arg118Cys) -, has been recurrently described in large FD screening studies of high-risk patients. Although the Cys118 allele is associated with high residual α-Gal activity in vitro, it has been classified as a pathogenic mutation, mainly on the basis of theoretical arguments about the chemistry of the cysteine residue. However its pathogenicity has never been convincingly demonstrated by pathology criteria. We reviewed the clinical, biochemical and histopathology data obtained from 22 individuals of Portuguese and Spanish ancestry carrying the Cys118 allele, including 3 homozygous females. Cases were identified either on the differential diagnosis of possible FD manifestations and on case-finding studies (n=11; 4 males), or on unbiased cascade screening of probands' close relatives (n=11; 3 males). Overall, those data strongly suggest that the GLA p.(Arg118Cys) variant does not segregate with FD clinical phenotypes in a Mendelian fashion, but might be a modulator of the multifactorial risk of cerebrovascular disease. The Cys118 allelic frequency in healthy Portuguese adults (n=696) has been estimated as 0.001, therefore not qualifying for "rare" condition.
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Enfermedad de Fabry/diagnóstico , Enfermedad de Fabry/etnología , Riñón/patología , alfa-Galactosidasa/genética , Adulto , Alelos , Sustitución de Aminoácidos , Codón/genética , Enfermedad de Fabry/complicaciones , Enfermedad de Fabry/epidemiología , Salud de la Familia , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Estructura Molecular , Mutación , FenotipoRESUMEN
INTRODUCTION: The objective of this retrospective study was to describe the short- and long-term patterns of IVIg use, safety, and response to treatment in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: Response to therapy was defined as an improvement of ≥ 1 point on the modified Rankin score at short- and mid-term visits. Patient status at long term was classified as remission, stability, or non-responder. RESULTS: Eighty-six patients were included; 60.5% responded at short term and 54.6% at mid-term. At long term, 25.6% of patients were in remission, 65.1% were stable, and 9.3% were non-responders. The only variable associated with remission was a better response during the first 6 months of follow-up. CONCLUSIONS: A significant percentage of patients did not require any additional drugs in the long term. This suggests that treatment effect or disease outcome may be stable over time, and treatment regimens should therefore be individualized to avoid overtreatment.
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Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/terapia , Potenciales de Acción/efectos de los fármacos , Adulto , Anciano , Evaluación de la Discapacidad , Estimulación Eléctrica , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Conducción Nerviosa/efectos de los fármacos , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/fisiopatología , Tiempo de Reacción/efectos de los fármacos , Tiempo de Reacción/fisiología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Chronic fatigue syndrome is characterised by intense fatigue, with duration of over six months and associated to other related symptoms. The latter include asthenia and easily induced tiredness that is not recovered after a night's sleep. The fatigue becomes so severe that it forces a 50% reduction in daily activities. Given its unknown aetiology, different hypotheses have been considered to explain the origin of the condition (from immunological disorders to the presence of post-traumatic oxidative stress), although there are no conclusive diagnostic tests. Diagnosis is established through the exclusion of other diseases causing fatigue. This syndrome is rare in childhood and adolescence, although the fatigue symptom per se is quite common in paediatric patients. Currently, no curative treatment exists for patients with chronic fatigue syndrome. The therapeutic approach to this syndrome requires a combination of different therapeutic modalities. The specific characteristics of the symptomatology of patients with chronic fatigue require a rapid adaptation of the educational, healthcare and social systems to prevent the problems derived from current systems. Such patients require multidisciplinary management due to the multiple and different issues affecting them. This document was realized by one of the Interdisciplinary Work Groups from the Institute for Rare Diseases, and its aim is to point out the main social and care needs for people affected with Chronic Fatigue Syndrome. For this, it includes not only the view of representatives for different scientific societies, but also the patient associations view, because they know the true history of their social and sanitary needs. In an interdisciplinary approach, this work also reviews the principal scientific, medical, socio-sanitary and psychological aspects of Chronic Fatigue Syndrome.
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Síndrome de Fatiga Crónica/diagnóstico , Adolescente , Adulto , Niño , Terapia Combinada , Diagnóstico Diferencial , Fatiga/diagnóstico , Síndrome de Fatiga Crónica/etiología , Síndrome de Fatiga Crónica/terapia , Femenino , Humanos , Hipersensibilidad/diagnóstico , Masculino , Educación del Paciente como Asunto , Participación del Paciente , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina , Pronóstico , Trastornos por Estrés Postraumático/diagnósticoRESUMEN
BACKGROUND AND OBJECTIVES: Steinert's disease or myotonic dystrophy type 1 (MD1), (OMIM 160900), is the most prevalent myopathy in adults. It is a multisystemic disorder with dysfunction of virtually all organs and tissues and a great phenotypical variability, which implies that it has to be addressed by different specialities with experience in the disease. The knowledge of the disease and its management has changed dramatically in recent years. This guide tries to establish recommendations for the diagnosis, prognosis, follow-up and treatment of the complications of MD1. MATERIAL AND METHODS: Consensus guide developed through a multidisciplinary approach with a systematic literature review. Neurologists, pulmonologists, cardiologists, endocrinologists, neuropaediatricians and geneticists have participated in the guide. RECOMMENDATIONS: The genetic diagnosis should quantify the number of CTG repetitions. MD1 patients need cardiac and respiratory lifetime follow-up. Before any surgery under general anaesthesia, a respiratory evaluation must be done. Dysphagia must be screened periodically. Genetic counselling must be offered to patients and relatives. CONCLUSION: MD1 is a multisystemic disease that requires specialised multidisciplinary follow-up.
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Distrofia Miotónica/diagnóstico , Estudios de Seguimiento , Humanos , Distrofia Miotónica/complicaciones , Guías de Práctica Clínica como AsuntoRESUMEN
Although treatment with alglucosidase alfa has helped improve the prognosis of patients with late-onset Pompe disease, both the development of the disease and the effectiveness of the treatment need to be monitored on a regular basis. This is the reason that has led a committee of Spanish experts to draw up a series of guidelines on how to follow up these patients. The committee proposes a model of follow-up tests for late-onset Pompe disease. First of all, the nutritional status and swallowing function must be evaluated. Second, and due to the variability of the clinical features, the committee recommends the simultaneous use of several scales to measure different functions and parameters. Thus, muscular force is assessed with the Medical Research Council scale; motor functioning, with the six-minute walk test and timed tests; disability, with the Rasch-built Pompe-specific Activity scale; respiratory functioning, with measurement of the forced vital capacity and oxygen saturation; and fatigue, with the fatigue intensity scale. Lastly, the safety and tolerability of enzyme replacement therapy are controlled by registering and treating the potential side effects and measurement of the anti-alglucosidase alfa antibodies. A number of different general recommendations are also included.
TITLE: Guia para el seguimiento de la enfermedad de Pompe de inicio tardio.Aunque el tratamiento con alglucosidasa alfa ha contribuido a mejorar el pronostico de los pacientes con enfermedad de Pompe de inicio tardio, es necesario hacer un seguimiento periodico de la evolucion de la enfermedad y de la eficacia del tratamiento. Por este motivo, un comite de expertos españoles ha elaborado una guia para el seguimiento de estos pacientes. El comite propone un modelo de pruebas de seguimiento para la enfermedad de Pompe de inicio tardio. En primer lugar, ha de valorarse el estado nutricional y la funcion deglutoria. En segundo lugar, y debido a la variabilidad del cuadro clinico, el comite recomienda el uso simultaneo de varias escalas que midan distintas funciones y parametros. De este modo, la fuerza muscular se evalua con la escala del Medical Research Council; la funcion motora, con la prueba de la marcha en seis minutos y pruebas cronometradas; la discapacidad, con la escala de actividad especifica de la enfermedad de Pompe construida segun el analisis de Rasch; la funcion respiratoria, con la medida de la capacidad vital forzada y la saturacion de oxigeno; y la fatiga, con la escala de intensidad de la fatiga. Por ultimo, la seguridad y la tolerabilidad del tratamiento enzimatico sustitutivo se controlan con el registro y tratamiento de los potenciales efectos adversos y la medicion de los anticuerpos antialglucosidasa alfa. Se incluyen tambien diversas recomendaciones generales.
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Terapia de Reemplazo Enzimático , Glucano 1,4-alfa-Glucosidasa/uso terapéutico , Enfermedad del Almacenamiento de Glucógeno Tipo II/tratamiento farmacológico , Adolescente , Edad de Inicio , Biomarcadores , Niño , Enfermedades del Sistema Digestivo/etiología , Evaluación de la Discapacidad , Manejo de la Enfermedad , Monitoreo de Drogas , Glucano 1,4-alfa-Glucosidasa/deficiencia , Enfermedad del Almacenamiento de Glucógeno Tipo II/clasificación , Enfermedad del Almacenamiento de Glucógeno Tipo II/complicaciones , Enfermedad del Almacenamiento de Glucógeno Tipo II/epidemiología , Humanos , Imagen por Resonancia Magnética , Fuerza Muscular , Estado Nutricional , Proteínas Recombinantes/uso terapéutico , Índice de Severidad de la Enfermedad , Capacidad VitalRESUMEN
Mitochondrial encephalomyopathies encompass a group of disorders that have impaired oxidative metabolism in skeletal muscles and central nervous system. Many compounds have been used in clinical trials on mitochondrial diseases, but the outcomes have been variable. It remains controversial whether treatment of mitochondrial diseases with coenzyme Q 10 is effective. This paper describes a case of mitochondrial myopathy, encephalopathy, lactic acidosis, strokelike episodes, and exercise intolerance successfully treated with coenzyme Q 10. Efficacy of this therapy in this patient is correlated to control of lactic acidosis and serum creatine kinase levels. Disappointingly, larger studies with coenzyme Q 10 failed to demonstrate a clear beneficial effect on the entire study population with regard to clinical improvement or several parameters of the oxidative metabolism. They suggest that the use of coenzyme Q in treatment of mitochondrial diseases should be confined to protocols. There is a confounding variation in phenotype and genotype, and the natural history of the disorders in individual patients is not accurately predictable. The unpredictable a priori efficacy of therapy suggests that a long-term trial of oral coenzyme Q may be warranted.
Asunto(s)
Acidosis Láctica/tratamiento farmacológico , Antioxidantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Síndrome MELAS/tratamiento farmacológico , Accidente Cerebrovascular/tratamiento farmacológico , Ubiquinona/análogos & derivados , Ubiquinona/uso terapéutico , Acidosis Láctica/etiología , Adulto , Bicarbonatos/sangre , Coenzimas , Creatina/sangre , Epilepsia/etiología , Femenino , Humanos , Concentración de Iones de Hidrógeno/efectos de los fármacos , Ácido Láctico/sangre , Síndrome MELAS/complicaciones , Metaanálisis como Asunto , Accidente Cerebrovascular/etiologíaRESUMEN
INTRODUCTION. The sympathetic skin response (SSR) has been used since its description in 1984 to test the integrity of the sympathetic autonomic nervous system to investigate peripheral and central nervous system diseases. AIM. To present a neurophysiological examination protocol for SSR and the normal parameters for a population of 100 normal subjects. SUBJECTS AND METHODS. To evaluate the characteristics of 200 SSR tests for 100 normal subjects adequately informed: latency, amplitude (peak to peak) and persistence. The subject lays supine and relaxed, with no visual nor auditory stimuli for several minutes. Cutaneous electrodes are used for stimulation and recording, the latter in palm (active) and back (reference) in both hands simultaneously (second interosseous space). The stimulus is applied in the glabela at irregular intervals. RESULTS. We studied 100 normal subjects aged 12 to 89 years (mean: 45.6), 21 men and 79 women. The parameters measured in the 200 SSR are: latency, 1.42 ± 0.03 s; amplitude, 2.44 ± 1.84 mV; persistence, 67.2 ± 19.8%. CONCLUSIONS. SSR is an objective, reproducible, measurable, easy to perform and unpainful for the patient and serves as a basis for further study of other diseases in which there is a dysfunction of the sympathetic autonomic nervous system.
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Respuesta Galvánica de la Piel/fisiología , Sistema Nervioso Simpático/fisiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Mano/inervación , Humanos , Masculino , Persona de Mediana Edad , Tiempo de Reacción , Valores de Referencia , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
Oculopharyngeal muscular dystrophy is an autosomal dominant adult-onset disease with several clinical features. The genetic cause is an expanded (GCN)n mutation coding for polyalanine. Severity and the age of onset are variable and may depend on the size of the unstable triplet. Our objectives were to correlate the genotypic and phenotypic features in 34 affected patients, and to complete the molecular analysis for a control Spanish population in order to confirm the (GCN)n polymorphism frequency observed in other populations. We found a correlation between impaired CPK levels and sex. No statistical differences were found when comparing the length in triplet expansion and other variables. The (GCN)n polymorphism's frequency observed in other countries could not be proven in ours. Moreover, no correlation was observed amongst the size of the mutation, the age of onset, and the phenotype. This fact suggests that other conditions apart from the already known genotype could influence the age of onset and the severity of the symptoms.
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Genotipo , Distrofia Muscular Oculofaríngea/diagnóstico , Distrofia Muscular Oculofaríngea/genética , Fenotipo , Proteína I de Unión a Poli(A)/genética , Anciano , Anciano de 80 o más Años , Alelos , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Distrofia Muscular Oculofaríngea/epidemiología , España/epidemiología , Expansión de Repetición de Trinucleótido/genéticaRESUMEN
Myotonia congenita is an inherited muscle disorder caused by mutations in the CLCN1 gene, a voltage-gated chloride channel of skeletal muscle. We have studied 48 families with myotonia, 32 out of them carrying mutations in CLCN1 gene and eight carry mutations in SCN4A gene. We have found 26 different mutations in CLCN1 gene, including 13 not reported previously. Among those 26 mutations, c.180+3A>T in intron 1 is present in nearly one half of the Spanish families in this series, the largest one analyzed in Spain so far. Although scarce data have been published on the frequency of mutation c.180+3A>T in other populations, our data suggest that this mutation is more frequent in Spain than in other European populations. In addition, expression in HEK293 cells of the new missense mutants Tyr137Asp, Gly230Val, Gly233Val, Tyr302His, Gly416Glu, Arg421Cys, Asn567Lys and Gln788Pro, demonstrated that these DNA variants are disease-causing mutations that abrogate chloride currents.
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Canales de Cloruro/genética , Salud de la Familia , Pruebas Genéticas/métodos , Mutación/genética , Miotonía/diagnóstico , Miotonía/genética , Adolescente , Adulto , Fenómenos Biofísicos/genética , Biofisica , Línea Celular Transformada , Niño , Estimulación Eléctrica , Electromiografía , Femenino , Humanos , Masculino , Potenciales de la Membrana/genética , Persona de Mediana Edad , Mutagénesis Sitio-Dirigida , Técnicas de Placa-Clamp , España , Transfección , Adulto JovenRESUMEN
TITLE: Como escribimos los neurologos.
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Escritura Médica/normas , Neurología , Terminología como Asunto , LenguajeRESUMEN
Chemotherapy-induced peripheral neuropathy (CIN) is a common toxicity of anticancer treatment and its incidence is growing. It significantly affects quality of life and is a dose-limiting factor that interferes with treatment. Its diagnosis can be established in clinical terms but some complementary tests can help when the diagnosis is difficult. There is still no proven method to prevent it that has become a standard of care in spite of the huge amount of investigation carried out in recent years. There are promising strategies that could help reduce the burden of this complication. This review will suggest an approach to the diagnosis of these disorders and provide an update on new therapies.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Enfermedades del Sistema Nervioso Periférico/terapia , Animales , Suplementos Dietéticos , Humanos , Modelos Biológicos , Fármacos Neuroprotectores/uso terapéutico , Sistema Nervioso Periférico/efectos de los fármacos , Sistema Nervioso Periférico/fisiología , Enfermedades del Sistema Nervioso Periférico/prevención & control , Compuestos de Platino/efectos adversos , Compuestos de Platino/farmacología , Vitaminas/uso terapéuticoRESUMEN
We report a 29-year-old patient with McArdle's disease and myasthenia gravis. She had been debilitated with McArdle's disease since childhood (with marked rhabdomyolysis) and was obese. Myasthenia gravis was diagnosed at 24 years of age. After 3 months of aerobic exercise training, her exercise capacity increased significantly and she regained the ability to live independently. We conclude that even patients with profound neuromuscular diseases may benefit from carefully prescribed exercise training.