ABSTRACT
Introducción: La esclerosis tuberosa (ET) es una enfermedad sistémica, de herencia autosómica dominante, ocasionada por mutaciones en dos genes (TSC1 y TSC2), que causan la aparición de tumores (angiolipomas [AML], angiofibromas, astrocitomas, etc.). La proliferación inadecuada y constante que existe en la ET puede ser bloqueada por inhibidores de la kinasa mTOR (mammalian target of rapamycin), como la rapamicina. Material y métodos: Se han incluido 17 pacientes afectados de ET y, al menos, un AML mayor de 2 cm de diámetro diagnosticado por resonancia magnética (RM). Han recibido tratamiento con rapamicina durante 12 meses. Los niveles plásmáticos se han mantenido entre 4 y 8 ng/dl. El tamaño del AML se ha monitorizado semestralmente mediante RM abdominal. Resultados: A los 12 meses de la inclusión, con la RM se ha objetivado una disminución del tamaño del AML en todos los pacientes incluidos, mostrando una reducción de, al menos, un 50% en el 82,4% (14/17; intervalo de confianza [IC] 95% [56,57%, 96,20%]). El porcentaje medio de reducción fue del 66,3% (IC95 [56,9%, 75,6%]; p <0,0001). Los principales efectos secundarios observados han sido: aftas orales (5/17); hipertrigliceridemia (3/17); microcitosis e hipocromía (3/17); diarrea (2/17); acné (1/17); pielonefritis aguda (1/17), y proteinuria (1/17). Conclusiones: Los datos clínicos preliminares sugieren que la rapamicina puede desempeñar un papel beneficioso en el tratamiento de la ET. Nuestra experiencia en 17 pacientes tratados durante 12 meses demuestra seguridad y eficacia en la reducción de AML (AU)
Background: Tuberous sclerosis (TS) is a systemic disease, with an autosomal dominant pattern of inheritance caused by mutations in two genes (TSC1 and TSC2) that cause tumours (angiomyolipomas [AML], angiofibromas, astrocytomas). Constant and inadequate proliferation occurring in TS may be blocked by mTOR inhibitors (mammalian target of rapamycin), such as rapamycin. Material and methods: At present, our study includes 17 patients with TS. All had at least one AML greater than 2cm in diameter diagnosed by MRI. They received rapamycin during 12 months. Plasma levels remained stable between 4-8ng/dl. The AML size was monitored every six months by abdominal MRI. Results: At 12 months of inclusion, MRI indicated a decrease in the size of AML in all patients showing at least a 50% reduction in 82.4% (14/17, 95% CI [56.57%, 96.20%]). The mean percent reduction was 66.3% (95% CI [56.9%, 75.6%], P<.0001). The major side effects observed were: oral aphthous ulcers (5/17); hypertriglyceridemia (3/17); microcytosis and hypochromia (3/17); diarrhea (2/17); acne (1/17); acute pyelonephritis (1/17); and proteinuria (1/17). Conclusions: These preliminary clinical data suggest that rapamycin can play a beneficial role in the treatment of TS. Our experience in 17 patients treated for 12 months demonstrates safety and efficacy in reducing AML volume (AU)
Subject(s)
Humans , Angiomyolipoma/drug therapy , Sirolimus/pharmacokinetics , Tuberous Sclerosis/drug therapy , TOR Serine-Threonine Kinases/antagonists & inhibitorsABSTRACT
La poliquistosis renal autosómica dominante (PQRAD) es la enfermedad renal hereditaria más frecuente. Sup r e v a l e n c i a e s t i m a d a e s d e u n o c a d a 8 0 0 p e r s o n a s .L o s pacientes con PQRAD constituyen un 8%aproximadamente de la población en diálisis o trasplante renal. El diagnóstico de la enfermedad es radiológico y/o genético. La posibilidad de realizar un diagnóstico genético directo de la PQRAD es actualmente una realidad en nuestro país, aunque por las características del gen PKD1no es un análisis sencillo ni económico. Debe estudiarse cada caso de forma individualizada con el fin de determinar la idoneidad de realizar un estudio genético y determinar qué tipo de estudio es el adecuado. El diagnóstico genético es de especial interés para los donantes vivos, para casos neonatales y para casos esporádicos. El diagnóstico genético permite ofrecer diagnóstico prenatal o preimplantacional en familias con casos severos de la enfermedad y también permitirá tratar la enfermedad, cuando exista un tratamiento específico, en aquellos casos dudosos que sin confirmación genética no serían candidatos a tratamiento (AU)
Autosomal dominant polycystic kidney disease (ADPKD) is the commonest renal inherited disorder. Its estimated prevalence is1 in 800 individuals. ADPKD patients constitute 8% of the population on dialysis or renal transplantation. The diagnosis of the disease can be made using radiological or genetic procedures. In Spain, we are now able to perform a direct genetic diagnosis of the disease, however it is neither an easy test nor cheap. This is why every case should be considered by means of an individualized approach to determine the appropriateness of genetic testing and to determine which genetic test is more adequate. Genetic testing in ADPKD is especially interesting for living donors, neonatal and sporadic cases. Genetic testing offers the chance to perform prenatal or preimplantation testing of embryos in families with severe disease. Also, the guarantee of a doubtless diagnosis will permit to treat sporadic cases, when treatment becomes available (AU)
Subject(s)
Humans , Polycystic Kidney, Autosomal Dominant/genetics , Pathology, Molecular/methods , Genetic Predisposition to Disease , Kidney Failure, Chronic/physiopathology , MutationABSTRACT
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disorder. Its estimated prevalence is 1 per 800 individuals. ADPKD patients constitute 8% of the population on dialysis or kidney transplantation. The disease can be diagnosed using radiological or genetic procedures. Direct genetic diagnosis of the disease can now be performed in Spain; however, it is not an easy or cheap test. This is why every case should be considered individually to determine whether genetic testing is appropriate, and to determine which genetic test is most adequate. Genetic testing in ADPKD is of special interest for living donors and neonatal and sporadic cases. Genetic testing offers the chance of performing prenatal or pre-implantation testing of embryos in families with severe cases of the disease. Also, this will enable the disease to be treated, when specific treatment becomes available, in cases that would not be candidates for treatment without genetic confirmation.
Subject(s)
Mutation , Polycystic Kidney, Autosomal Dominant/diagnosis , Age of Onset , DNA Mutational Analysis , Databases, Genetic , Diagnostic Imaging/economics , Genetic Counseling , Genetic Linkage , Humans , Molecular Diagnostic Techniques/economics , Mosaicism , Polycystic Kidney, Autosomal Dominant/economics , Polycystic Kidney, Autosomal Dominant/epidemiology , Polycystic Kidney, Autosomal Dominant/genetics , Preimplantation Diagnosis/economics , Preimplantation Diagnosis/methods , Prenatal Diagnosis/economics , Prenatal Diagnosis/methods , RNA, Messenger/genetics , Spain , TRPP Cation Channels/geneticsABSTRACT
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