RESUMEN
OBJECTIVES: To assess natural history and 12-month change of a series of scales and functional outcome measures in a cohort of 117 patients with primary mitochondrial myopathy (PMM). METHODS: Twelve months follow-up data of 117 patients with PMM were collected. We analysed the 6-min walk test (6MWT), timed up-and-go test (× 3) (3TUG), five-times sit-to-stand test (5XSST), timed water swallow test (TWST), and test of masticating and swallowing solids (TOMASS) as functional outcome measures; the Fatigue Severity Scale and West Haven-Yale Multidimensional pain inventory as patient-reported outcome measures. PMM patients were divided into three phenotypic categories: mitochondrial myopathy (MiMy) without extraocular muscles involvement, pure chronic progressive external ophthalmoplegia (PEO) and PEO&MiMy. As 6MWT is recognized to have significant test-retest variability, we calculated MCID (minimal clinically important difference) as one third of baseline 6 min walking distance (6MWD) standard deviation. RESULTS: At 12-month follow-up, 3TUG, 5XSST and FSS were stable, while TWST and the perceived pain severity (WHYMPI) worsened. 6MWD significantly increased in the entire cohort, especially in the higher percentiles and in PEO patients, while was substantially stable in the lower percentile (< 408 m) and MiMy patients. This increase in 6MWD was considered not significant, as inferior to MCID (33.3 m). NMDAS total score showed a slight but significant decline at 12 months (0.9 point). The perceived pain severity significantly worsened. Patients with PEO performed better in functional measures than patients with PEO&MiMy or MiMy, and had lower values of NMDAS. CONCLUSIONS: PMM patients showed a slow global decline valued by NMDAS at 12 months; 6MWT was a more reliable measurement below 408 m, substantially stable at 12 months. PEO patients had better motor performance and lower NMDAS than PEO&MiMy and MiMy also at 12 months of follow-up.
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Miopatías Mitocondriales , Oftalmoplejía Externa Progresiva Crónica , Humanos , Estudios de Seguimiento , Prueba de Paso/métodos , Miopatías Mitocondriales/complicaciones , Miopatías Mitocondriales/diagnóstico , Factores de Tiempo , CaminataRESUMEN
INTRODUCTION: Both prevalence and clinical features of the various movement disorders in adults with primary mitochondrial diseases are unknown. METHODS: Based on the database of the "Nation-wide Italian Collaborative Network of Mitochondrial Diseases", we reviewed the clinical, genetic, neuroimaging and neurophysiological data of adult patients with primary mitochondrial diseases (n = 764) where ataxia, myoclonus or other movement disorders were part of the clinical phenotype. RESULTS: Ataxia, myoclonus and movement disorders were present in 105/764 adults (13.7%), with the onset coinciding or preceding the diagnosis of the mitochondrial disease in 49/105 (46.7%). Ataxia and parkinsonism were the most represented, with an overall prevalence at last follow-up of 59.1% and 30.5%, respectively. Hyperkinetic movement disorders were reported in 15.3% at last follow-up, being the less common reported movement disorders. The pathogenic m.8344A > G and POLG variants were always associated with a movement disorder, while LHON variants and mtDNA single deletions were more commonly found in the subjects who did not present a movement disorder. The most common neuroimaging features were cortical and/or cerebellar atrophy, white matter hyperintensities, basal ganglia abnormalities and nigro-striatal degeneration. Almost 70% of patients with parkinsonism responded to dopaminergic therapy, mainly levodopa, and 50% with myoclonus were successfully treated with levetiracetam. CONCLUSION: Movement disorders, mainly ataxia and parkinsonism, are important findings in adult primary mitochondrial diseases. This study underlies the importance of looking for a mitochondrial etiology in the diagnostic flowchart of a movement disorder and may help direct genetic screening in daily practice.
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Enfermedades Mitocondriales , Trastornos del Movimiento , Mioclonía , Trastornos Parkinsonianos , Humanos , Enfermedades Mitocondriales/complicaciones , Enfermedades Mitocondriales/epidemiología , Enfermedades Mitocondriales/genética , Trastornos del Movimiento/diagnóstico , Trastornos del Movimiento/epidemiología , Trastornos del Movimiento/genética , Trastornos Parkinsonianos/complicaciones , Trastornos Parkinsonianos/epidemiología , Trastornos Parkinsonianos/genética , FenotipoAsunto(s)
ADN Mitocondrial/genética , Cálculos Renales/genética , Enfermedades Mitocondriales/diagnóstico , Adulto , Análisis Mutacional de ADN , Femenino , Humanos , Cálculos Renales/diagnóstico , Masculino , Persona de Mediana Edad , Enfermedades Mitocondriales/complicaciones , Enfermedades Mitocondriales/genética , Mutación , RecurrenciaRESUMEN
Mitochondrial diseases are a group of rare multisystem disorders characterized by genetic heterogeneity and pleomorphic clinical manifestations. The clinical burden may be heavy for patients and their caregivers. There are no therapies of proven efficacy until now and a multidisciplinary supportive care is therefore necessary. Since the common pathogenic mechanism is the insufficient energy production by defective mitochondria, nutrition may play a crucial role. However, no guidelines are still available. The article reports the current evidence, highlighting nutrition both as support and as therapy. The estimate of nutritional status, energy needs and nutritional behaviors are firstly discussed. Then, we go in-depth on the scientific rationale and the clinical evidence of the use of anti-oxidants and enzyme-cofactors in the clinical practice. In particular, we analyze the role of Coenzyme Q10, Creatine monohydrate, α-lipoic acid, riboflavin, arginine and citrulline, folinic acid, carnitine, vitamin C, K, and E. Every attempt at nutritional intervention should be made knowing patient's disease and focusing on his/her energy and nutrients' requirements. For this reason, clinicians expert in mitochondrial medicine and clinical nutritionists should work together to ameliorate care in these fragile patients.
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Enfermedades Mitocondriales/terapia , Apoyo Nutricional , Arginina/administración & dosificación , Trastornos de Deglución/prevención & control , Dieta Alta en Grasa , Metabolismo Energético , Humanos , Mitocondrias/genética , Mitocondrias/metabolismo , Ácido Tióctico/administración & dosificación , Ubiquinona/administración & dosificación , Ubiquinona/análogos & derivadosRESUMEN
Ocular myopathy, typically manifesting as progressive external ophthalmoplegia (PEO), is among the most common mitochondrial phenotypes. The purpose of this study is to better define the clinical phenotypes associated with ocular myopathy. This is a retrospective study on a large cohort from the database of the "Nation-wide Italian Collaborative Network of Mitochondrial Diseases". We distinguished patients with ocular myopathy as part of a multisystem mitochondrial encephalomyopathy (PEO-encephalomyopathy), and then PEO with isolated ocular myopathy from PEO-plus when PEO was associated with additional features of multisystemic involvement. Ocular myopathy was the most common feature in our cohort of mitochondrial patients. Among the 722 patients with a definite genetic diagnosis, ocular myopathy was observed in 399 subjects (55.3%) and was positively associated with mtDNA single deletions and POLG mutations. Ocular myopathy as manifestation of a multisystem mitochondrial encephalomyopathy (PEO-encephalomyopathy, n = 131) was linked to the m.3243A>G mutation, whereas the other "PEO" patients (n = 268) were associated with mtDNA single deletion and Twinkle mutations. Increased lactate was associated with central neurological involvement. We then defined, among the PEO group, as "pure PEO" the patients with isolated ocular myopathy and "PEO-plus" those with ocular myopathy and other features of neuromuscular and multisystem involvement, excluding central nervous system. The male proportion was significantly lower in pure PEO than PEO-plus. This study reinforces the need for research on the role of gender in mitochondrial diseases. The phenotype definitions here revisited may contribute to a more homogeneous patient categorization, useful in future studies and clinical trials.
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Oftalmoplejía Externa Progresiva Crónica/genética , Oftalmoplejía Externa Progresiva Crónica/fisiopatología , Adulto , Edad de Inicio , ADN Polimerasa gamma/genética , ADN Mitocondrial , Femenino , GTP Fosfohidrolasas/genética , Estudios de Asociación Genética , Humanos , Italia , Masculino , Mutación , Oftalmoplejía Externa Progresiva Crónica/diagnóstico , Oftalmoplejía Externa Progresiva Crónica/epidemiología , Fenotipo , Estudios Retrospectivos , Adulto JovenRESUMEN
Miller Fisher syndrome (MFS) is considered to be an uncommon variant of Guillain-Barré Syndrome. The disease is clinically characterized by acute ataxia of limbs, areflexia and ophthalmoplegia, although the set of symptoms and signs can be quite heterogeneous, with a benign and monophasic course. We describe a case of recurrent MFS where there have been four clinical episodes occurred with complete remission after each relapse. Last recurrence was treated with oral steroids. The reported frequency of recurrent MFS in literature is variable as well as the best treatment in these cases. We add a new case treated with steroid and we perform a review of the literature.
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Síndrome de Miller Fisher , Femenino , Humanos , Masculino , Síndrome de Miller Fisher/tratamiento farmacológico , Recurrencia , Esteroides/uso terapéuticoRESUMEN
BACKGROUND AND PURPOSE: Peripheral neuropathy in mitochondrial diseases (MDs) may vary from a subclinical finding in a multisystem syndrome to a severe, even isolated, manifestation in some patients. METHODS: To investigate the involvement of the peripheral nervous system in MDs extensive electrophysiological studies were performed in 109 patients with morphological, biochemical and genetic diagnosis of MD [12 A3243G progressive external ophthalmoplegia (PEO)/mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), 16 myoclonic epilepsy with ragged-red fibres (MERRF), four mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), 67 PEO with single or multiple deletions of mitochondrial DNA, 10 others]. RESULTS: A neuropathy was found in 49 patients (45%). The incidence was very high in MNGIE (100%), MELAS (92%) and MERRF (69%), whilst 28% of PEO patients had evidence of peripheral involvement. The most frequent abnormality was a sensory axonal neuropathy found in 32/49 patients (65%). A sensory-motor axonal neuropathy was instead detected in 16% of the patients and sensory-motor axonal demyelinating neuropathy in 16%. Finally one Leigh patient had a motor axonal neuropathy. It is interesting to note that the great majority had preserved tendon reflexes and no sensory disturbances. CONCLUSIONS: In conclusion, peripheral involvement in MD is frequent even if often mild or asymptomatic. The correct identification and characterization of peripheral neuropathy through electrophysiological studies represents another tile in the challenge of MD diagnosis.
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Enfermedades Mitocondriales/complicaciones , Enfermedades del Sistema Nervioso Periférico/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Axones/patología , Axones/fisiología , Niño , Femenino , Humanos , Masculino , Nervio Mediano/patología , Nervio Mediano/fisiopatología , Persona de Mediana Edad , Mitocondrias/genética , Enfermedades Mitocondriales/patología , Enfermedades Mitocondriales/fisiopatología , Enfermedades del Sistema Nervioso Periférico/patología , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Síndrome , Adulto JovenRESUMEN
OBJECTIVE: A multicentre observational study was aimed to assess the prevalence of late-onset Pompe disease (LOPD) in a large high-risk population, using the dried blood spot (DBS) as a main screening tool. DESIGN/METHODS: 17 Italian neuromuscular centres were involved in the late-onset Pompe early diagnosis (LOPED) study. Inclusion criteria were: (1) age ≥5â years, (2) persistent hyperCKaemia and (3) muscle weakness at upper and/or lower limbs (limb-girdle muscle weakness, LGMW). Acid α-glucosidase (GAA) activity was measured separately on DBS by fluorometric as well as tandem mass spectrometry methods. A DBS retest was performed in patients resulted positive at first assay. For the final diagnosis, GAA deficiency was confirmed by a biochemical assay in skeletal muscle, whereas genotype was assessed by GAA molecular analysis. RESULTS: In a 14-month period, we studied 1051 cases: 30 positive samples (2.9%) were detected by first DBS screening, whereas, after retesting, 21 samples were still positive. Biochemical and molecular genetic studies finally confirmed LOPD diagnosis in 17 cases (1.6%). The median time from the onset of symptoms/signs to diagnosis was 5â years. Among those patients, 35% showed presymptomatic hyperCKaemia and 59% showed hyperCKaemia+LGMW, whereas 6% manifested with LGMW. CONCLUSIONS: LOPED study suggests that GAA activity should be accurately screened by DBS in all patients referring for isolated hyperCKaemia and/or LGMW. A timely diagnosis was performed in five patients with presymptomatic hyperCKaemia, but two had already manifested with relevant changes on muscle morphology and MRI. Consequently, enzyme replacement therapy was started in 14/17 patients, including the 2 patients still clinically presymptomatic but with a laboratory evidence of disease progression.
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Enfermedad del Almacenamiento de Glucógeno Tipo II/diagnóstico , Adulto , Edad de Inicio , Creatina Quinasa/sangre , Diagnóstico Precoz , Femenino , Fluorometría , Enfermedad del Almacenamiento de Glucógeno Tipo II/genética , Enfermedad del Almacenamiento de Glucógeno Tipo II/terapia , Humanos , Masculino , Persona de Mediana Edad , Debilidad Muscular/etiología , Músculo Esquelético/patología , Patología Molecular/métodos , Reproducibilidad de los Resultados , Riesgo , Espectrometría de Masas en Tándem , alfa-Glucosidasas/genéticaRESUMEN
Congenital myopathy related to mutations in myosin MyHC IIa gene (MYH2) is a rare neuromuscular disease. A single dominant missense mutation has been reported so far in a family in which the affected members had congenital joint contractures at birth, external ophthalmoplegia and proximal muscle weakness. Afterward only additional 4 recessive mutations have been identified in 5 patients presenting a mild non-progressive early-onset myopathy associated with ophthalmoparesis. We report a new de novo MYH2 missense mutation in a baby affected by a congenital myopathy characterized by severe dysphagia, respiratory distress at birth and external ophthalmoplegia. We describe clinical, histopathological and muscle imaging findings expanding the clinical and genetic spectrum of MYH2-related myopathy.
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Debilidad Muscular/patología , Enfermedades Musculares/genética , Mutación Missense/genética , Cadenas Pesadas de Miosina/genética , Miosina Tipo V/genética , Niño , Proteínas del Citoesqueleto/genética , Femenino , Humanos , Datos de Secuencia Molecular , Debilidad Muscular/genética , Enfermedades Musculares/diagnóstico , Enfermedades Musculares/patología , Cadenas Pesadas de Miosina/química , Miosina Tipo V/química , Oftalmoplejía/genética , Oftalmoplejía/patología , Análisis de Secuencia de ProteínaRESUMEN
Fatigue and exercise intolerance are common symptoms of mitochondrial diseases, but difficult to be clinically assessed. New methods to quantify these rather common complaints are strongly needed in the clinical practice. Coenzyme Q10 administration and aerobic exercise may improve exercise intolerance, but more definite studies are still pending. Herein, we have revised "how to measure" and "how to treat" these symptoms of mitochondrial patients. Subsequently, we reviewed the clinical data of the 1164 confirmed mitochondrial patients present in the Italian nation-wide database of mitochondrial disease, with special regard to exercise intolerance. We observed that more of 20% of mitochondrial patients complain of exercise intolerance. This symptom seems to be frequently associated with specific patient groups and/or genotypes. Ragged red fibers and COX-negative fibers are more often present in subjects with exercise intolerance, whereas lactate levels could not predict this symptom. Multicenter efforts are strongly needed for rare disorders such as mitochondrial diseases, and may represent the basis for more rigorous longitudinal studies.
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Ejercicio Físico/fisiología , Fatiga , Enfermedades Mitocondriales , Fatiga/diagnóstico , Fatiga/genética , Humanos , Enfermedades Mitocondriales/diagnóstico , Enfermedades Mitocondriales/genética , Mutación/genética , Ubiquinona/análogos & derivados , Ubiquinona/metabolismoRESUMEN
BACKGROUND AND PURPOSE: Duchenne muscular dystrophy carriers represent a rare condition that needs to be recognized because of the possible implications for prenatal diagnosis. Muscle biopsy is currently the diagnostic instrument of choice in sporadic patients. We wanted to verify whether muscle magnetic resonance imaging (MRI) could identify a pattern of involvement suggestive of this condition and whether it was similar to that reported in Duchenne and Becker muscular dystrophy. METHODS: Evaluation of pelvic and lower limb MRI scans of 12 dystrophinopathy carriers was performed. RESULTS: We found a frequent involvement of the quadratus femoris, gluteus maximus and medius, biceps femoris long head, adductor magnus, vasti and paraspinal muscles, whilst the popliteus, iliopsoas, recti abdominis, sartorius, and gracilis were relatively spared. Asymmetry was a major feature on MRI; it could be detected significantly more often than with sole clinical examination and even in patients without weakness. CONCLUSIONS: The pattern we describe here is similar to that reported in Duchenne and Becker muscular dystrophy, although asymmetry represents a major distinctive feature. Muscle MRI was more sensitive than clinical examination for detecting single muscle involvement and asymmetry. Further studies are needed to verify the consistency of this pattern in larger cohorts and to assess whether muscle MRI can improve diagnostic accuracy in carriers with normal dystrophin staining on muscle biopsy.
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Heterocigoto , Imagen por Resonancia Magnética/métodos , Músculo Esquelético/patología , Distrofia Muscular de Duchenne/patología , Adulto , Enfermedades Asintomáticas , Estudios de Cohortes , Femenino , Humanos , Extremidad Inferior/patología , Persona de Mediana Edad , Distrofia Muscular de Duchenne/genética , Pelvis/patología , Estudios RetrospectivosRESUMEN
The objective of this study was to describe a large Italian cohort of patients with late-onset glycogen storage disease type 2 (GSDII) at various stages of disease progression and to evaluate the clinical effectiveness of alglucosidase alpha enzyme replacement therapy (ERT). Previous studies showed in late-onset patients ERT efficacy against placebo and variable response in uncontrolled studies. Seventy-four juvenile or adult GSDII patients were treated with ERT in a multicenter open label, non-randomized study, from 12 months up to 54 months. Recombinant human alpha glucosidase (rh-GAA) was injected by intravenous route at 20 mg/kg every second week. Patients were divided into three groups according to ERT duration: Group A received treatment for 12-23 months (n = 16), Group B for 24-35 months (n = 14), and Group C for more than 36 months (n = 44). Clinical assessment included a 6-min walk test (6MWT), forced vital capacity (FVC), the Walton and Gardner-Medwin score, the number of hours of ventilation, body mass index, echocardiography and blood creatine kinase (CK). Included in our cohort were 33 males and 41 females (M:F = 0.8:1), with a mean age at first symptoms of 28.3 years (range 2-55 years) and a mean age of 43 years at study entry (range 7-72 years). Seven wheelchair bound patients, as well as 27 patients requiring ventilation support, were included. After treatment we could observe an increase in distance walked on the 6MWT in the large majority of patients (48/58; 83%), with an overall mean increase of 63 m (from 320 ± 161 to 383 ± 178 m). After treatment in the majority of patients FVC was improved or unchanged (45/69; 65%). In ventilated patients we observed an improvement in average number of hours off the ventilator (from 15.6 to 12.1 h). Six patients stopped mechanical ventilation and two others started it. The effect of therapy was not related to ERT duration. Nine of 64 patients (13%) that underwent to echocardiography showed a variable degree of cardiac hypertrophy (left ventriculum or septum), and a positive effect was observed after 36 months of ERT in one adult case. Discontinuation of treatment occurred in four patients: one drop-off case, one patient died for a sepsis after 34 months of treatment and two patients stopped ERT for worsening of general clinical condition. Mild adverse effects were observed in four cases (5%). This study represents the largest cohort of late-onset GSDII patients treated with ERT, and confirm a positive effect of treatment. These results, obtained in a large case series on therapy, indicate a favourable effect of ERT therapy, even in more advanced stage of the disease.
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Terapia de Reemplazo Enzimático/métodos , Enfermedad del Almacenamiento de Glucógeno Tipo II/tratamiento farmacológico , Observación , alfa-Glucosidasas/uso terapéutico , Adolescente , Adulto , Anciano , Índice de Masa Corporal , Niño , Estudios de Cohortes , Ecocardiografía , Femenino , Enfermedad del Almacenamiento de Glucógeno Tipo II/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Italia , Masculino , Persona de Mediana Edad , Examen Físico , Respiración/efectos de los fármacos , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Factores de Tiempo , Resultado del Tratamiento , Capacidad Vital , Caminata/fisiología , Adulto JovenAsunto(s)
Creatina Quinasa/sangre , Pierna/fisiopatología , Movimiento/fisiología , Síndrome de las Piernas Inquietas/sangre , Síndrome de las Piernas Inquietas/enzimología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos del Movimiento/sangre , Trastornos del Movimiento/diagnóstico , Trastornos del Movimiento/enzimología , Síndrome de las Piernas Inquietas/diagnóstico , Factores de Tiempo , Adulto JovenAsunto(s)
Leucoencefalitis Hemorrágica Aguda/diagnóstico , Adolescente , Adulto , Encéfalo/patología , Diagnóstico Diferencial , Imagen de Difusión por Resonancia Magnética , Estudios de Seguimiento , Humanos , Aumento de la Imagen , Procesamiento de Imagen Asistido por Computador , Virus de la Influenza A , Gripe Humana/diagnóstico , Imagen por Resonancia Magnética , Masculino , Recurrencia , Remisión Espontánea , Inconsciencia/diagnósticoRESUMEN
BACKGROUND: Paroxysmal nonkinesigenic dyskinesia (PNKD) is a rare disorder characterized by episodic hyperkinetic movement attacks. We have recently identified mutations in the MR-1 gene causing familial PNKD. METHODS: We reviewed the clinical features of 14 kindreds with familial dyskinesia that was not clearly induced by movement or during sleep. Of these 14 kindreds, 8 had MR-1 mutations and 6 did not. RESULTS: Patients with PNKD with MR-1 mutations had their attack onset in youth (infancy and early childhood). Typical attacks consisted of a mixture of chorea and dystonia in the limbs, face, and trunk, and typical attack duration lasted from 10 minutes to 1 hour. Caffeine, alcohol, and emotional stress were prominent precipitants. Attacks had a favorable response to benzodiazepines, such as clonazepam and diazepam. Attacks in families without MR-1 mutations were more variable in their age at onset, precipitants, clinical features, and response to medications. Several were induced by persistent exercise. CONCLUSIONS: Paroxysmal nonkinesigenic dyskinesia (PNKD) should be strictly defined based on age at onset and ability to precipitate attacks with caffeine and alcohol. Patients with this clinical presentation (which is similar to the phenotype initially reported by Mount and Reback) are likely to harbor myofibrillogenesis regulator 1 (MR-1) gene mutations. Other "PNKD-like" families exist, but atypical features suggests that these subjects are clinically distinct from PNKD and do not have MR-1 mutations. Some may represent paroxysmal exertional dyskinesia.
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Corea/genética , Corea/fisiopatología , Predisposición Genética a la Enfermedad/genética , Proteínas Musculares/genética , Mutación/genética , Adolescente , Adulto , Edad de Inicio , Cafeína/efectos adversos , Niño , Preescolar , Corea/metabolismo , Análisis Mutacional de ADN , Distonía/genética , Distonía/metabolismo , Distonía/fisiopatología , Etanol/efectos adversos , Femenino , Marcadores Genéticos/genética , Pruebas Genéticas , Genotipo , Humanos , Masculino , Linaje , Penetrancia , Estrés Psicológico/complicacionesRESUMEN
BACKGROUND: Periodic paralyses and paramyotonia congenita are rare disorders causing disabling weakness and myotonia. Mutations in sodium, calcium, and potassium channels have been recognized as causing disease. OBJECTIVE: To analyze the clinical phenotype of patients with and without discernible genotype and to identify other mutations in ion channel genes associated with disease. METHODS: The authors have reviewed clinical data in patients with a diagnosis of hypokalemic periodic paralysis (56 kindreds, 71 patients), hyperkalemic periodic paralysis (47 kindreds, 99 patients), and paramyotonia congenita (24 kindreds, 56 patients). For those patients without one of the classically known mutations, the authors analyzed the entire coding region of the SCN4A, KCNE3, and KCNJ2 genes and portions of the coding region of the CACNA1S gene in order to identify new mutations. RESULTS: Mutations were identified in approximately two thirds of kindreds with periodic paralysis or paramyotonia congenita. The authors found differences between the disorders and between those with and without identified mutations in terms of age at onset, frequency of attacks, duration of attacks, fixed proximal weakness, precipitants of attacks, myotonia, electrophysiologic studies, serum potassium levels, muscle biopsy, response to potassium administration, and response to treatment with acetazolamide. CONCLUSIONS: Hypokalemic periodic paralysis, hyperkalemic periodic paralysis, and paramyotonia congenita may be distinguished based on clinical data. This series of 226 patients (127 kindreds) confirms some clinical features of this disorder with notable exceptions: In this series, patients without mutations had a less typical clinical presentation including an older age at onset, no changes in diet as a precipitant, and absence of vacuolar myopathy on muscle biopsy.
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Parálisis Periódica Hipopotasémica/diagnóstico , Trastornos Miotónicos/diagnóstico , Parálisis Periódica Hiperpotasémica/diagnóstico , Adolescente , Adulto , Niño , Preescolar , Análisis Mutacional de ADN , Femenino , Genotipo , Humanos , Parálisis Periódica Hipopotasémica/genética , Masculino , Persona de Mediana Edad , Trastornos Miotónicos/genética , Canal de Sodio Activado por Voltaje NAV1.4 , Parálisis Periódica Hiperpotasémica/genética , Fenotipo , Canales de Potasio de Rectificación Interna/genética , Canales de Potasio con Entrada de Voltaje/genética , Canales de Sodio/genéticaRESUMEN
Myasthenia gravis is a chronic disease of neuromuscular transmission caused by loss of acetylcholine receptors. It can be found in association with other autoimmune disorders. We report the case of a 47-yr-old woman affected by Myasthenia gravis who complained of fever, progressive weakness of proximal limb muscle, arthritis and Raynauds phenomenon and dyspnea. Chest X-rays and CT scan showed an interstitial lung disease; laboratory data indicated an inflammatory picture and increased serum muscle enzymes. Evaluation for infectious, metabolic, iatrogenic and neoplastic aetiologies was unrevealing. The patients clinical condition together with positive results on antisynthetase antibody assay lead to the diagnosis of antisynthetase syndrome. To our knowledge, this is the first report on the association of Myasthenia gravis with antisynthetase syndrome.