Ataxia de Friedreich

Descripción General

Definiciones

• Ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia: movimientos anormales y descoordinados
• Ataxias hereditarias: grupo heterogéneo de afecciones hereditarias que tienen como síntoma cardinal la ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia, generalmente secundaria a una lesión o disfunción del cerebelo
• Ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia de Friedreich: trastorno autosómico recesivo caracterizado por degeneración espinocerebelosa

Genética y fisiopatología

• Una mutación en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum el gen FXN del cromosoma 9 da lugar a una expansión de la repetición de trinucleótidos de guanina-adenina-adenina (GAA).
  • Normalmente, la secuencia GAA dentro del gen FXN se repite entre 7–34 veces.
  • En EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia de Friedreich, la secuencia se repite aproximadamente entre 70–1 300 veces.
• Esta expansión de triple repetición provoca el silenciamiento del gen y reduce la producción de una proteína llamada frataxina al AL Amyloidosis 5–35% de lo normal.
  • La frataxina es una proteína mitocondrial y una pieza clave en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la producción de adenosín trifosfato (ATP).
  • La deficiencia de frataxina provoca daños celulares a través de diferentes mecanismos.
  • Las células más frecuentemente dañadas por la deficiencia de frataxina son las neuronas, las células del miocardio y las células beta del páncreas.
  • La principal patogénesis neuronal es la muerte de las neuronas distales a las proximales, conocida como “fenómeno de muerte axonal retrógrada”.
  • Los LOS Neisseria principales lugares de afectación neuronal son los LOS Neisseria nervios periféricos, las columnas dorsales, el tracto corticoespinal y los LOS Neisseria tractos espinocerebelosos lateral y ventral.

Epidemiología

• Es la ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia autosómica recesiva más común (50% de los LOS Neisseria casos)
• Incidencia en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum Estados Unidos: 1 de cada 40 000
• Más común en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum los LOS Neisseria caucásicos
• Inicio de los LOS Neisseria síntomas generalmente < 20 años de edad

Presentación Clínica

Características neurológicas

• Tríada (muy sugestiva): ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia + arreflexia + reflejos plantares extensores
• Marcha atáxica:
  • Generalmente, es el síntoma que se presenta en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la adolescencia
  • Afecta a ambos miembros inferiores
  • Empeoramiento progresivo de la marcha, la cual se vuelve lenta y torpe, después de haber desarrollado una marcha normal
  • Combinación de 2 tipos de marcha:
    • Cerebelosa: de base amplia, cambio constante de posición para mantener el equilibrio
    • Déficit sensorial: exacerba la marcha de base ancha y la marcha equina
• Otros síntomas son:
  • Debilidad motora
  • Pérdida del sentido de la vibración y de la posición; pérdida eventual de las sensaciones de tacto ligero, dolor Dolor Inflammation y temperatura
  • Pérdida de los LOS Neisseria reflejos tendinosos profundos
  • Reflejo plantar extensor
  • Ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia del tronco y brazos
  • Temblor de los LOS Neisseria músculos faciales y de los LOS Neisseria brazos
  • Dependencia de una silla de ruedas en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la 1era a 2da década de vida
  • Disartria y disfagia

Características no neurológicas

• Cifoescoliosis (hasta 80%)
• Cardiomiopatía hipertrófica (> 50%): signos de hipertrofia ventricular como soplos sistólicos de eyección
• Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus (aproximadamente 10%)
• Pie cavo y/o pie equinovaro (pie zambo)
• Pérdida visual y auditiva
• Deterioro cognitivo leve

Diagnóstico

Pruebas genéticas

• Confirman el diagnóstico
• Indicaciones:
  • Diagnóstico prenatal para padres con un hijo afectado
  • Cualquier paciente sospechoso de padecer la enfermedad

Imagenología

• Resonancia magnética (RM) (imagenología de elección):
  • Atrofia de la médula espinal cervical con mínima evidencia de atrofia cerebelosa
  • La atrofia cerebelosa es un hallazgo tardío.
• Electrocardiograma ( ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG)) y ultrasonido cardíaco para buscar signos de cardiomiopatía hipertrófica
• Pruebas de glucosa en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum suero para la diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus
• Los LOS Neisseria estudios de conducción nerviosa pueden mostrar una leve reducción en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la velocidad.

Tratamiento

• No hay tratamiento definitivo
• Intervención multidisciplinaria (e.g., neurología, medicina física, cardiología, ortopedia, endocrinología)
• El inicio temprano de la terapia ocupacional y la fisioterapia ayuda a preservar la funcionalidad.
• Omaveloxolona:
  • Aprobada en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum 2023
  • Utilizada para ralentizar la progresión de la enfermedad.
• Pronóstico:
  • La edad promedio de fallecimiento es de 37 años.
  • Un mayor número de repeticiones GAA se asocia a una aparición más temprana de la enfermedad y a una mayor probabilidad de cardiomiopatía y diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus.
  • La cardiomiopatía es la causa más frecuente de muerte.
  • Las mujeres tienen un pronóstico significativamente mejor.

Diagnóstico Diferencial

El diagnóstico diferencial de la ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia de Friedreich incluye las siguientes afecciones:

• Ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia telangiectasia Telangiectasia Permanent dilation of preexisting blood vessels creating small focal red lesions, most commonly in the skin or mucous membranes. It is characterized by the prominence of skin blood vessels, such as vascular spiders. Chronic Venous Insufficiency hereditaria: ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia cerebelosa degenerativa con malformaciones vasculares oculocutáneas ( telangiectasia Telangiectasia Permanent dilation of preexisting blood vessels creating small focal red lesions, most commonly in the skin or mucous membranes. It is characterized by the prominence of skin blood vessels, such as vascular spiders. Chronic Venous Insufficiency) y máculas café con leche. Se hereda genéticamente y se transmite con un patrón autosómico recesivo. Los LOS Neisseria pacientes presentan una marcha inusual de base estrecha, a diferencia de la ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia de Friedreich, en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la que la marcha es de base ancha. Existe una elevada incidencia de cáncer en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum pacientes con ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia telangiectasia Telangiectasia Permanent dilation of preexisting blood vessels creating small focal red lesions, most commonly in the skin or mucous membranes. It is characterized by the prominence of skin blood vessels, such as vascular spiders. Chronic Venous Insufficiency hereditaria (principalmente leucemia y linfoma). No existen tratamientos curativos y el pronóstico es malo. La edad promedio de fallecimiento de los LOS Neisseria pacientes con ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia telangiectasia Telangiectasia Permanent dilation of preexisting blood vessels creating small focal red lesions, most commonly in the skin or mucous membranes. It is characterized by the prominence of skin blood vessels, such as vascular spiders. Chronic Venous Insufficiency hereditaria es de 25 años.
• Enfermedad de Charcot-Marie-Tooth: un espectro de afecciones heredadas genéticamente que afectan a los LOS Neisseria nervios periféricos. Los LOS Neisseria síntomas clínicos comunes incluyen neuropatía periférica progresiva, debilidad distal y atrofia muscular. Las pruebas genéticas y la electromiografía son importantes herramientas de diagnóstico para detectar esta afección. El tratamiento es de soporte. Si bien es frecuente requerir silla de ruedas, la mayoría de los LOS Neisseria pacientes conservan su capacidad ambulatoria y la esperanza de vida no se acorta.
• Ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia con deficiencia de vitamina E: aunque suele observarse en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum pacientes con deficiencias alimentarias, existe una forma genética de esta afección que está causada por mutaciones en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum el gen de la proteína de transferencia del alfa-tocoferol. Esta mutación se hereda con un patrón autosómico recesivo, al AL Amyloidosis igual que la ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia de Friedreich. Al AL Amyloidosis igual que la ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia de Friedreich, puede presentarse con neuropatía y pérdida de la marcha normal. Además, la afección presenta hallazgos cutáneos como la retinitis pigmentaria. El tratamiento con altas dosis de vitamina E es curativo en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum estos pacientes.