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INTRODUCTION: The incidence of myotonic dystrophy type 1 (DM1), a disease with great phenotypic variety, in our region is unknown. This study aims to estimate the incidence of DM1 at our hospital (a reference centre in Aragon, Spain) and to identify the characteristics of our population (genotype-phenotype correlation). METHODS: Retrospective, descriptive study of 459 patients classified according to the number of CTG repeats, as follows: normal (5-35), premutation (36-50), protomutation (51-80), small expansions (81-150), intermediate expansions (151-1000), and large expansions (> 1000). Furthermore, according to clinical phenotype, patients were categorised as unaffected (5-50 CTG repeats), mild form or asymptomatic (51-150), classical form (151-1000), and severe form (> 1000). RESULTS: The incidence of DM1 was 20.61 cases per million person-years (95% CI, 19.59-21.63). An inverse correlation was observed between the number of CTG repeats and the age at genetic diagnosis (ρ = -0.547; 95% CI, -0.610 to -0.375; P < .001). CTG5 was the most frequent polymorphic allele in healthy individuals. Of all patients with DM1, 28.3% presented the mild or asymptomatic form, 59.1% the classical form, and 12.6% the severe form. Inheritance was maternal in 35.1% of cases, paternal in 59.4%, and uncertain in 5.5%. In mild forms, frontal balding in men was the most prevalent phenotypic trait, as well as myotonia and cataracts, while in the classical form, ptosis, facial weakness, voice and pronunciation alterations, myotonia, and fatigue/sleepiness were most frequent. CONCLUSIONS: The incidence of DM1 in Aragon is significant. Multidisciplinary study of the phenotype of patients with DM1 is key to early diagnosis and personalised management.
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INTRODUCTION: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. PATIENTS AND METHODS: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. RESULTS: We gathered data from a total of 1933 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 938 patients were men (48.5%) and 995 were women (51.5%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. CONCLUSIONS: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.
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Ataxia Cerebelosa , Paraplejía Espástica Hereditaria , Masculino , Humanos , Femenino , Persona de Mediana Edad , Paraplejía Espástica Hereditaria/epidemiología , Paraplejía Espástica Hereditaria/genética , Estudios Transversales , Estudios Retrospectivos , España/epidemiologíaAsunto(s)
Vértebras Cervicales , Apófisis Odontoides/anomalías , Enfermedades de la Médula Espinal/patología , Enfermedades de la Columna Vertebral/patología , Adulto , Articulación Atlantoaxoidea/diagnóstico por imagen , Vértebras Cervicales/cirugía , Femenino , Humanos , Imagen por Resonancia Magnética , Procedimientos Neuroquirúrgicos , Paresia , Enfermedades de la Médula Espinal/diagnóstico por imagen , Enfermedades de la Médula Espinal/cirugía , Enfermedades de la Columna Vertebral/diagnóstico por imagen , Enfermedades de la Columna Vertebral/cirugíaRESUMEN
INTRODUCTION: The incidence of myotonic dystrophy type1 (DM1), a disease with great phenotypic variety, in our region is unknown. This study aims to estimate the incidence of DM1 at our hospital (a reference centre in Aragon, Spain) and to identify the characteristics of our population (genotype-phenotype correlation). METHODS: Retrospective, descriptive study of 459 patients classified according to the number of CTG repeats, as follows: normal (5-35), premutation (36-50), protomutation (51-80), small expansions (81-150), intermediate expansions (151-1000), and large expansions (>1000). Furthermore, according to clinical phenotype, patients were categorised as unaffected (5-50 CTG repeats), mild form or asymptomatic (51-150), classical form (151-1000), and severe form (>1000). RESULTS: The incidence of DM1 was 20.61 cases per million person-years (95%CI: 19.59-21.63). An inverse correlation was observed between the number of CTG repeats and the age at genetic diagnosis (ρ=-0.547; 95%CI: -0.610 to -0.375; P<.001). CTG5 was the most frequent polymorphic allele in healthy individuals. Of all patients with DM1, 28.3% presented the mild or asymptomatic form, 59.1% the classical form, and 12.6% the severe form. Inheritance was maternal in 35.1% of cases, paternal in 59.4%, and uncertain in 5.5%. In mild forms, frontal balding in men was the most prevalent phenotypic trait, as well as myotonia and cataracts, while in the classical form, ptosis, facial weakness, voice and pronunciation alterations, myotonia, and fatigue/sleepiness were most frequent. CONCLUSIONS: The incidence of DM1 in Aragon is significant. Multidisciplinary study of the phenotype of patients with DM1 is key to early diagnosis and personalised management.
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INTRODUCTION: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. PATIENTS AND METHODS: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. RESULTS: We gathered data from a total of 1.809 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 920 patients were men (50.8%) and 889 were women (49.2%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. CONCLUSIONS: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.
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Introducción: Se desconoce la incidencia de la distrofia miotónica tipo 1 (DM1), enfermedad con gran variedad fenotípica, en nuestra región. El objetivo de nuestro trabajo es estimar la incidencia de DM1 en nuestro centro (referencia en Aragón) e identificar las características propias de nuestra población (correlación genotipo-fenotipo). Métodos: Estudio descriptivo retrospectivo de 459 pacientes clasificados según número de repeticiones CTG en: normal (5-35), premutado (36-50), protomutado (51-80), pequeñas expansiones (81-150), intermedias (151-1.000) y grandes (> 1.000). Además, según el fenotipo mostrado, se categorizaron como: no afectos (5-50 CTG), forma leve o asintomática (51-150 CTG), clásica (151-1.000 CTG) y severa (> 1.000 CTG). Resultados: La incidencia de DM1 fue de 20,61 (IC 95%: 19,59-21,63) casos por millón de individuos-año. Se evidenció una correlación inversa entre el número de CTG y la edad al diagnóstico genético (ρ = −0,547; IC 95%: −0,610 a −0,375; p < 0,001). El CTG5 fue el alelo polimórfico más frecuente en sanos. Del total de afectos, el 28,3% presentaron la forma leve o asintomática, el 59,1% la forma clásica y el 12,6% la forma severa. El 35,1% presentaron herencia materna, el 59,4% herencia paterna y el 5,5% herencia incierta. En las formas leves la calvicie frontal en varones fue el rasgo fenotípico más prevalente, junto con miotonía y cataratas, mientras que en la clásica predominó la ptosis palpebral, la debilidad facial, las alteraciones en la voz y la pronunciación, la miotonía y la sensación de cansancio/somnolencia. Conclusiones: La incidencia de DM1 es relevante en Aragón. La revisión multidisciplinar del fenotipo de pacientes con DM1 es clave para un diagnóstico precoz y medicina personalizada.(AU)
Introduction: The incidence of myotonic dystrophy type 1 (DM1), a disease with great phenotypic variety, in our region is unknown. This study aims to estimate the incidence of DM1 at our hospital (a reference centre in Aragon, Spain) and to identify the characteristics of our population (genotype-phenotype correlation). Methods: Retrospective, descriptive study of 459 patients classified according to the number of CTG repeats, as follows: normal (5-35), premutation (36-50), protomutation (51-80), small expansions (81-150), intermediate expansions (151-1000), and large expansions (> 1000). Furthermore, according to clinical phenotype, patients were categorised as unaffected (5-50 CTG repeats), mild form or asymptomatic (51-150), classical form (151-1000), and severe form (> 1000). Results: The incidence of DM1 was 20.61 cases per million person-years (95% CI: 19.59-21.63). An inverse correlation was observed between the number of CTG repeats and the age at genetic diagnosis (ρ = −0.547; 95% CI: −0.610 to −0.375; P < .001). CTG5 was the most frequent polymorphic allele in healthy individuals. Of all patients with DM1, 28.3% presented the mild or asymptomatic form, 59.1% the classical form, and 12.6% the severe form. Inheritance was maternal in 35.1% of cases, paternal in 59.4%, and uncertain in 5.5%. In mild forms, frontal balding in men was the most prevalent phenotypic trait, as well as myotonia and cataracts, while in the classical form, ptosis, facial weakness, voice and pronunciation alterations, myotonia, and fatigue/sleepiness were most frequent. Conclusions: The incidence of DM1 in Aragon is significant. Multidisciplinary study of the phenotype of patients with DM1 is key to early diagnosis and personalised management.(AU)
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Humanos , Masculino , Femenino , Distrofia Miotónica/clasificación , Distrofia Miotónica/diagnóstico , Variación Biológica Poblacional , Reacción en Cadena de la Polimerasa , Incidencia , Neurología , Enfermedades del Sistema Nervioso , Estudios RetrospectivosRESUMEN
An association between limb-girdle muscular dystrophy and autoimmune polyglandular syndrome type 1 (APS1), in three sisters born to consanguineous parents, is presented. The components of APS1 in these patients were hypoparathyroidism, autoimmune adrenal insufficiency, primary hypogonadism and mucocutaneous candidiasis. A muscle biopsy performed on the first patient showed over 40 % of trabeculated fibers, suggesting the diagnosis of myopathy with trabeculated fibers (MTF). Intracranial calcification was found in the second patient; and epilepsy, and several other minor components of APS1, in the third; cataracts were found in the last two patients. The clinical manifestations and inheritance of MTF and APS1 are reviewed. While recessive mutations in the AIRE gene (21q22.3) cause APS1, genetic transmission of hereditary MTF has not been investigated in depth. Mutations in CRYAA, a gene that shares the same locus as AIRE, may cause recessive inheritance of cataracts. Thus, the proposal of this article is that linkage of contiguous genes that includes the AIRE gene, might be responsible for the association of both diseases in these three patients. Additional involvement of CRYAA, that possibly causes cataracts in two of the patients, might support this hypothesis, due to the proximity of this gene to AIRE. The genes COL6A1 and COL6A2, localized in 21q22.3, are discarded as transmitters of MTF in these cases, on clinical criteria. The authors wish to draw attention to the association between limb-girdle muscular dystrophy and APS1, since it has been very rarely reported in the medical literature.
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Fibras Musculares Esqueléticas/patología , Músculo Esquelético/patología , Enfermedades Musculares/fisiopatología , Poliendocrinopatías Autoinmunes/fisiopatología , Adolescente , Adulto , Encéfalo/patología , Comorbilidad , Femenino , Humanos , Enfermedades Musculares/genética , Mutación , Poliendocrinopatías Autoinmunes/genéticaRESUMEN
The authors present a case of adult GM2 gangliosidosis, B1 enzymatic type. The main clinical features found were cerebellar ataxia, proximal lower limb weakness and myokymia. The neurological examination, and the biochemical, electrophysiologic and imaging studies are all described. Decreased activity of the enzyme beta-hexosaminidase A in the metabolism of the sulfate substrate 4-MU-NAGS was found in serum. Global cerebellar atrophy was observed in a cranial nuclear magnetic resonance. The electrophysiologic study showed continuous spontaneous activity integrated by myokymia and neuromyotonic discharges in addition to signs of acute and chronic denervation. Disappearance of the myokymia and improvement in the ataxia were attained with the use of the GABAergic drugs gabapentin and tiagabine. The authors try to explain the clinical improvement obtained with the drugs by relating their mechanisms of action to the central nervous system neurotransmitter alterations proposed for this disease.
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Acetatos/uso terapéutico , Aminas , Ataxia/tratamiento farmacológico , Ataxia/etiología , Ácidos Ciclohexanocarboxílicos , Antagonistas de Aminoácidos Excitadores/uso terapéutico , Agonistas del GABA/uso terapéutico , Gangliosidosis GM2/complicaciones , Miocimia/etiología , Ácidos Nipecóticos/uso terapéutico , Ácido gamma-Aminobutírico , Adulto , Ataxia/diagnóstico , Cerebelo/patología , Gabapentina , Gangliosidosis GM2/diagnóstico , Humanos , Masculino , Miocimia/diagnóstico , Miocimia/tratamiento farmacológico , Tiagabina , Tomografía Computarizada por Rayos X , beta-N-Acetilhexosaminidasas/metabolismoRESUMEN
A case of Guillain-Barré with unusual autonomic dysfunction at its onset, that consisted of constipation and hypertension, followed by adynamic ileus and flaccid paraparesis with areflexia limited to the lower limbs, is presented. Inappropriate secretion of antidiuretic hormone and hyperprolactinemia were demonstrated, which resolved spontaneously afterwards. The adynamic ileus resolved and the paraparesis improved with gastric aspiration and intravenous immunoglobulin administration, only to worsen eighty days later. Paraparesis worsened, accompanied by hypertension, an abnormal hypotensive response to captopril and limb pain. The whole clinical picture resolved after a second course of intravenous immunoglobulin. Unusual clinical aspects of Guillain-Barré syndrome found in this case are reviewed, such as paraparesis, prolonged adynamic ileus and endocrine abnormalities, comparing them with available data from the neurological literature. Differential diagnosis with myelopathy, metabolic and paraneoplasic neuropathies, POEMS syndrome, chronic inflammatory demyelinating polyneuropathy and recurrent Guillain-Barré syndrome are commented on. Hyperprolactinemia is proposed as a marker, either of adenopituitary denervation or of the autoimmune response, in the course of this disease.
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Síndrome de Guillain-Barré/complicaciones , Hiperprolactinemia/etiología , Ileus/etiología , Paraparesia/etiología , Anciano , Femenino , HumanosRESUMEN
The case of a 35-year-old woman with diaphragmatic myoclonus of four year duration is presented. The myoclonus deteriorated with anxiety, menstruation and orthostatism. It was frequently accompanied by urinary retention or incontinence. Several pharmacologic agents were shown to be ineffective until the myoclonus was suppressed with a combination of gabapentin and tiagabine. In this article, the respiratory center is proposed as the original focus of the myoclonus, a deficit of gamma-aminobutyric acid (GABA) in brainstem structures as its neurochemical substrate, and GABAergic enhancement as an effective therapeutic measure. The clinical manifestations, etiology, ancillary studies and treatment of diaphragmatic myoclonus are reviewed. Experimental evidence on the anatomical localization, physiology and neurochemistry of the respiratory center is examined. The authors try to relate some of the patient's clinical findings to the experimental data found in the medical literature. The action mechanisms of gabapentin and tiagabine are examined and these drugs are proposed as effective means of enhancing GABAergic neurotransmission and treating diseases with increased inspiratory drive.
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Aminas , Ácidos Ciclohexanocarboxílicos , Diafragma/fisiopatología , Mioclonía/diagnóstico , Mioclonía/fisiopatología , Ácido gamma-Aminobutírico , Acetatos/farmacología , Acetatos/uso terapéutico , Adulto , Anticonvulsivantes/farmacología , Anticonvulsivantes/uso terapéutico , Diafragma/efectos de los fármacos , Femenino , Agonistas del GABA/farmacología , Agonistas del GABA/uso terapéutico , Gabapentina , Humanos , Mioclonía/tratamiento farmacológico , Ácidos Nipecóticos/farmacología , Ácidos Nipecóticos/uso terapéutico , TiagabinaRESUMEN
A 72-year-old man presented with a chronic illness constituted by muscle rigidity affecting his lower limbs, trunk and neck, either spontaneous or triggered by stimuli, together with a spastic paraparesis, manual amyotrophy and pseudobulbar syndrome. The electrophysiologic study showed continuous motor unit activity integrated by normal motor unit potentials. Biochemical and imaging results were normal. These data suggest the diagnosis of idiopathic progressive encephalomyelitis with rigidity. Following administration of gabapentin (2000 mg daily), muscle rigidity and electromyographic continuous motor unit activity were suppressed. Transient drowsiness was the only side effect. The authors have tried to relate these findings to those found in the literature.
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Acetatos/uso terapéutico , Aminas , Ácidos Ciclohexanocarboxílicos , Encefalomielitis/tratamiento farmacológico , Encefalomielitis/fisiopatología , Rigidez Muscular/tratamiento farmacológico , Rigidez Muscular/fisiopatología , Ácido gamma-Aminobutírico , Anciano , Antiparkinsonianos/uso terapéutico , Electrofisiología , Encefalomielitis/diagnóstico , Gabapentina , Humanos , MasculinoAsunto(s)
Aminas/uso terapéutico , Antiparkinsonianos/uso terapéutico , Clonidina/análogos & derivados , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Encefalomielitis/tratamiento farmacológico , Rigidez Muscular/tratamiento farmacológico , Ácido gamma-Aminobutírico/uso terapéutico , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Encefalomielitis/fisiopatología , Agonistas del GABA/uso terapéutico , Gabapentina , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Rigidez Muscular/fisiopatología , Ácidos Nipecóticos/uso terapéutico , TiagabinaRESUMEN
Introducción. Los canales de calcio dependientes de voltaje (CCDV) son complejos heteromultiméricos que median el ingreso de calcio en la célula en respuesta a cambios en el potencial de membrana. La subunidad α1A, que forma el conducto iónico propio de los canales de calcio voltajedependientes de tipo P/Q (CCP/Q), es codificada por el gen CACNA1A. Las subunidades auxiliares β, α2δ y γ, comunes a otros CCDV, modulan la actividad de α1A. Los CCP/Q intervienen en procesos de supervivencia, excitabilidad y plasticidad de las neuronas y median el proceso de neurotransmisión rápida en el sistema nervioso central y periférico. Su máxima expresión se da en las células de Purkinje y en el hipocampo. Métodos. En este trabajo se revisan la estructura y modulación de los CCP/Q en el sistema nervioso, así como las enfermedades causadas por alteraciones de éstos. Resultados. Las alteraciones de los CCP/Q, tanto congénitas como adquiridas, causan enfermedades neurológicas de difícil tratamiento, como la ataxia espinocerebelosa tipo 6, ataxia episódica tipo 2 y la degeneración cerebelosa paraneoplásica, migraña hemipléjica familiar, epilepsia generalizada convulsiva, epilepsia tipo ausencia con punta-onda a 3 c/s y síndrome miasténico de Lambert-Eaton. La caracterización electrofisiológica de los CCP/Q anómalos ha demostrado en cada caso menor capacidad de transporte iónico que la de CCP/Q nativos. Conclusión. Futuras investigaciones deberían promover el desarrollo de fármacos capaces de restaurar la función de los CCP/Q con el fin de tratar las patologías causadas por alteración de los mismos
Introduction. Voltage-dependent calcium channels (VDCC) are hetero-multimeric complexes that mediate calcium influx into cells in response to changes in membrane potential. The α1A subunit, encoded by the CACNA1A gene, is the pore-forming structure specific to the neuronal P/Q-type voltage-dependent calcium channels (P/QCC), present exclusively in neurons. The ancillary subunits β, α2δ and γ, which are common to other VDCC, modulate α1A activity. P/QCC are involved in neuronal plasticity and survival, and mediate fast neurotransmission in the central and peripheral nervous system. Their highest levels of expression are found in the Purkinje cell layer of the cerebellum and in the hippocampus. Methods. Congenital and acquired disturbances of the P/QCCs lay behind some neurological diseases, such as spinocerebellar ataxia type 6, episodic ataxia type 2 and paraneoplastic cerebellar degeneration; familial hemiplegic migraine; generalized convulsive epilepsy, generalized absence epilepsy and myasthenic syndrome of Lambert-Eaton. Conclusion. In this article, the structure and modulation of normal P/QCCs, and the neurological diseases caused by disturbances in these are reviewed. Electrophysiological characterization of mutated P/QCCs has yielded decreased calcium conductance in every case, compared with wild type channels. Research about calcium channelopathies should clarify how altered channel function produces disease and lead to new treatments for these conditions
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Humanos , Animales , Canales de Calcio Tipo P/fisiología , Canales de Calcio Tipo Q/fisiología , Ataxias Espinocerebelosas/fisiopatología , Migraña con Aura/fisiopatología , Síndromes Paraneoplásicos/fisiopatología , Modelos Animales de EnfermedadRESUMEN
En este trabajo se presenta la asociación de distrofia muscular de cinturas con síndrome poliglandular autoinmune tipo 1 (SPA 1) en tres hermanas, hijas de padres consanguíneos. En las tres pacientes, el SPA 1 estuvo constituido por hipoparatiroidismo, insuficiencia suprarrenal, hipogonadismo primario y candidiasis mucocutánea. La biopsia muscular en una paciente reveló el 40 % de fibras trabeculares, sugiriendo el diagnóstico de miopatía con fibras trabeculares (MFT). Otras manifestaciones fueron calcificaciones intracraneales en la segunda paciente, epilepsia y múltiples componentes adicionales de SPA 1 en la tercera, y cataratas en estas dos. En este estudio se revisan las características clínicas y los mecanismos hereditarios del SPA 1 y la MFT. Mientras que el SPA 1 se transmite con herencia autosómico recesiva por mutaciones en el gen AIRE, localizado en 21q22.3, no se conoce la transmisión genética de la MFT hereditaria. Mutaciones en el gen CRYAA, ubicado en el mismo locus que AIRE, pueden transmitir cataratas con herencia recesiva. Se propone en consecuencia que la asociación de MFT con el SPA 1 en estas tres pacientes fuera transmitida por ligamiento de genes contiguos, que debería incluir el gen AIRE. La participación adicional del gen CRYAA en dos casos apoyaría esta hipótesis por su proximidad con el gen AIRE. Se descarta que estos casos de distrofia muscular estén transmitidos por los genes COL6A 1 y COL6A2, causantes de miopatía y situados en 21 q22.3, en base a criterios clínicos. Se pretende, en suma, destacar la asociación entre SPA 1 y distrofia muscular de cinturas por haber sido muy raramente mencionada en la literatura neurológica
An association between limb-girdle muscular dystrophy and autoimmune polyglandular syndrome type 1 (APS 1), in three sisters born to consanguineous parents, is presented. The components of APS 1 in these patients were hypoparathyroidism, autoimmune adrenal insufficiency, primary hypogonadism and mucocutaneous candidiasis. A muscle biopsy performed on the first patient showed over 40 % of trabeculated fibers, suggesting the diagnosis of myopathy with trabeculated fibers (MTF). Intracranial calcification was found in the second patient; and epilepsy, and several other minar components of APS1, in the third; cataracts were found in the last two patients. The clinical manifestations and inheritance of MTF and APS 1 are reviewed. While recessive mutations in the AIRE gene (21q22.3) cause APS 1, genetic transmission of hereditary MTF has not been investigated in depth. Mutations in CRY AA, a gene that shares the same locus as AIRE, may cause recessive inheritance of cataracts. Thus, the proposal of this article is that linkage of contiguous genes that includes the AIRE gene, might be responsible far the association of both diseases in these three patients. Additional involvement of CRYAA, that possibly causes cataracts in two of the patients, might support this hypothesis, due to the proximity of this gene to AIRE. The genes COL6A1 and COL6A2, localized in 21q22.3, are discarded as transmitters of MTF in these cases, on clinical criteria. The authors wish to draw attention to the association between limb-girdle muscular dystrophy and APS1, since it has been very rarely reported in the medical literature
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Femenino , Adulto , Adolescente , Humanos , Fibras Musculares Esqueléticas/patología , Músculo Esquelético/patología , Enfermedades Musculares/fisiopatología , Enfermedades Musculares/genética , Poliendocrinopatías Autoinmunes/fisiopatología , Mutación , Poliendocrinopatías Autoinmunes/genética , Comorbilidad , Telencéfalo/patologíaRESUMEN
Se presenta un caso de gangliosidosis GM2 de tipo enzimático B1 con fenotipo del adulto cuya expresión clínica está caracterizada por ataxia cerebelosa, debilidad muscular proximal de las extremidades inferiores y mioquimias. Se describen los hallazgos clínicos y los datos complementarios de tipo bioquímico, electrofisiológico y de imagen.Entre éstos se encontró actividad reducida de la enzima -hexosaminidasa A frente al sustrato sulfatado 4-MU-NAGS en suero, atrofia cerebelosa global en la resonancia magnética craneal, y en el estudio electrofisiológico, actividad espontánea continua en forma de descargas mioquímicas y neuromiotónicas, así como signos de denervación aguda y crónica. Se observó desaparición de las mioquimias y mejoría en la ataxia con la administración de los fármacos GABAérgicos gabapentina y tiagabina. Se intenta explicar la eficacia de estos fármacos, no utilizados previamente en el tratamiento de la gangliosidosis GM2, revisando sus mecanismos de acción e intentando relacionarlos con las alteraciones de la neurotransmisión en el sistema nervioso central propuestas para esta enfermedad. (AU)
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Adulto , Masculino , Humanos , Tomografía Computarizada por Rayos X , Antagonistas de Aminoácidos Excitadores , Agonistas del GABA , Miocimia , Gangliosidosis GM2 , beta-N-Acetilhexosaminidasas , Ataxia , Cerebelo , Acetatos , Ácidos NipecóticosRESUMEN
Se describe el caso de un paciente de 72 años de edad que presentó un proceso de evolución crónica constituido, esencialmente, por rigidez muscular de tronco, cuello y extremidades inferiores, exacerbada por estímulos tanto exógenos como endógenos, junto con paraparesia espástica, amiotrofia de las manos y síndrome seudobulbar. El estudio electrofisiológico evidenció una actividad muscular continua en forma de potenciales de unidad motora normales. Las pruebas complementarias bioquímicas y de imagen fueron normales. Estos datos apuntan al diagnóstico de encefalomielitis progresiva con rigidez, sin asociación con otra enfermedad. La administración de gabapentina a dosis de 2.000 mg/día suprimió la rigidez muscular y la actividad muscular continua en el estudio electromiográfico, con somnolencia transitoria como único efecto secundario. Se ha realizado una revisión bibliográfica sobre esa entidad, con la que se intentan relacionar los principales aspectos clínicos, neurofisiológicos y terapéuticos de nuestros hallazgos (AU)