Arbor, Vol 194, No 789 (2018)

Las enfermedades raras en las patologías neurometabólicas


https://doi.org/10.3989/arbor.2018.789n3003

Julio Montoya
Universidad de Zaragoza - Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) - Instituto de Investigación Sanitaria de Aragón, España
orcid http://orcid.org/0000-0003-1770-6299

Joaquín Arenas
Hospital 12 de Octubre (i+12) - Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), España
orcid http://orcid.org/0000-0002-2877-5049

Eduardo Ruiz-Pesini
Fundación ARAID - Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) - Instituto de Investigación Sanitaria de Aragón, España
orcid http://orcid.org/0000-0002-0269-7337

Miguel A. Martín-Casanueva
Hospital 12 de Octubre (i+12) - Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), España
orcid http://orcid.org/0000-0003-4741-772X

Resumen


Las miopatías metabólicas son un grupo de trastornos genéticos que disminuyen la capacidad del músculo esquelético para utilizar sustratos energéticos y sintetizar ATP. Estas alteraciones pueden clasificarse en tres tipos fundamentalmente: i) trastornos del metabolismo de los carbohidratos (del glucógeno y de la glucosa), ii) defectos del metabolismo lipídico, y iii) alteraciones de la fosforilación oxidativa –OXPHOS-. Las dos primeras se deben a deficiencias enzimáticas de las rutas metabólicas de degradación y síntesis de glúcidos y lípidos y muestran diversas manifestaciones clínicas, pero una buena parte de ellas cursan con intolerancia al ejercicio. Aunque un buen número de pacientes con estos trastornos musculares presentan síntomas en la infancia, el diagnóstico normalmente se retrasa hasta la segunda y tercera década de la vida. Por tanto, reconocer las características clínicas de estas deficiencias conduce a un diagnóstico precoz y a un mejor tratamiento. Las enfermedades mitocondriales son un grupo de trastornos originados por una deficiencia en la síntesis de ATP a través del sistema de fosforilación oxidativa. Este sistema está formado por proteínas codificadas en los dos genomas de la célula (nuclear y mitocondrial) y, por tanto, pueden presentar un modelo de herencia mendeliano o materno. En esta revisión se describirán las características especiales del sistema genético mitocondrial y las principales mutaciones que causan enfermedades en humanos.

Palabras clave


Glucogenosis musculares; miopatías lipídicas; intolerancia al ejercicio; DNA mitocondrial; DNA nuclear; enfermedades mitocondriales; mitocondria; sistema de fosforilación oxidativa

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