ABSTRACT
Background and objective: Fabry disease is an X-linked multisystemic lysosomal-storage condition. We describe a large family with a novel GLA mutation: p.M187R/g7219 T > G. Patients and methods: Anamnesis/physical-exam, blood/urine analysis, a-Gal-A activity and/or genetic study of at-risk individuals and multidisciplinary evaluation in confirmed cases. Results: 4 males and 13 heterozygous-females displayed the mutation. Cardiac/renal/neurological disease was diagnosed at a mean age of 41/29/39 years in males and 51/56/46 years in females. Onset mean age was 20 years versus 42 years. 9/15 had cardiomyopathy. Delta wave suggestive of accessory pathway was identified in 1 male and 2 females. 1 female had cardiac arrest (ventricular fibrillation, 61 years). 2 females and 1 male died suddenly (63, 64 and 57 years). Cardiac-subscore of Mainz Severity- Score-Index was severe for males and females over 40 years. 4/15(26%) developed early renal disease. 2 males needed dialysis. 1 male died at 69 years in spite of kidney-heart transplant. Conclusion: We describe the largest genetically confirmed Spanish family using multidisciplinary evaluation and MSSI calculation. The novel mutation p.M187R/g7219 T > G is associated with a particularly malignant cardiac phenotype in males and females over 40 years. Severity was higher than that of the largest Spanish FOS-cohort. Short-PR with delta is being reported for the first time (AU)
Fundamento y objetivo: La enfermedad de Fabry es un trastorno sistémico por depósito lisosomal ligado a X. Describimos una familia grande con una mutación nueva en GLA: p.M187R/g7219 T > G. Pacientes y Métodos: Anamnesis/exploración, análisis sangre/orina), actividad alfa-Gal-A y/o estudio genético a individuos en riesgo y evaluación multidisciplinar de casos confirmados. Resultados: Cuatro varones/12 mujeres presentaban la mutación. Se diagnosticó enfermedad cardiaca/ renal/neurológica a los 41/29/39 años como media en varones, y a los 51/56/46 años en mujeres. La media de inicio fue 20 años frente a 42. Presentaban miocardiopatı' a 9/15. Se identificó onda delta indicativa de vía accesoria en un varón y 2 mujeres. Una mujer sufrió parada cardiorrespiratoria (fibrilación ventricular, 61 años). Dos mujeres y un varón murieron súbitamente (63, 64 y 57 años, respectivamente). El subscore cardiaco del Mainz Severity Score Index (MSSI) fue grave en hombres y mujeres mayores de 40 años. Presentaron enfermedad renal temprana 4/15 (26%). Dos varones precisaron diálisis. Un varón murió a los 69 años pese a trasplante cardiorrenal. Conclusión: Describimos la mayor familia española confirmada gene' ticamente con evaluación multidisciplinar y cálculo del MSSI. La nueva mutación p.M187R/g7219 T > G asocia un fenotipo cardiaco especialmente grave en hombres y mujeres mayores de 40 años. La gravedad fue superior a la de la mayor cohorte-FOS española publicada. Se describen por primera vez ondas delta asociadas a PR-corto (AU)
Subject(s)
Humans , Male , Female , Fabry Disease/genetics , Mutation/genetics , Phenotype , Severity of Illness Index , Risk Factors , Genetic Markers , Genetic Predisposition to DiseaseABSTRACT
BACKGROUND AND OBJECTIVE: Fabry disease is an X-linked multisystemic lysosomal-storage condition. We describe a large family with a novel GLA mutation: p.M187R/g7219 T>G. PATIENTS AND METHODS: Anamnesis/physical-exam, blood/urine analysis, α-Gal-A activity and/or genetic study of at-risk individuals and multidisciplinary evaluation in confirmed cases. RESULTS: 4 males and 13 heterozygous-females displayed the mutation. Cardiac/renal/neurological disease was diagnosed at a mean age of 41/29/39 years in males and 51/56/46 years in females. Onset mean age was 20 years versus 42 years. 9/15 had cardiomyopathy. Delta wave suggestive of accessory pathway was identified in 1 male and 2 females. 1 female had cardiac arrest (ventricular fibrillation, 61 years). 2 females and 1 male died suddenly (63, 64 and 57 years). Cardiac-subscore of Mainz Severity-Score-Index was severe for males and females over 40 years. 4/15(26%) developed early renal disease. 2 males needed dialysis. 1 male died at 69 years in spite of kidney-heart transplant. CONCLUSION: We describe the largest genetically confirmed Spanish family using multidisciplinary evaluation and MSSI calculation. The novel mutation p.M187R/g7219 T>G is associated with a particularly malignant cardiac phenotype in males and females over 40 years. Severity was higher than that of the largest Spanish FOS-cohort. Short-PR with delta is being reported for the first time.
Subject(s)
Fabry Disease/epidemiology , Mutation, Missense , Point Mutation , alpha-Galactosidase/genetics , Adult , Age of Onset , Amino Acid Substitution , Arrhythmias, Cardiac/etiology , Brain/pathology , Enzyme Replacement Therapy , Eye Diseases/etiology , Fabry Disease/complications , Fabry Disease/drug therapy , Fabry Disease/genetics , Fabry Disease/pathology , Female , Genotype , Heart Arrest/etiology , Heart Transplantation , Humans , Hypertrophy, Left Ventricular/etiology , Kidney/pathology , Kidney Diseases, Cystic/etiology , Kidney Failure, Chronic/etiology , Kidney Failure, Chronic/surgery , Kidney Transplantation , Male , Middle Aged , Myocardium/pathology , Pedigree , Spain/epidemiology , alpha-Galactosidase/therapeutic useABSTRACT
An ischaemic infarction of the anterior inferior cerebellar artery (AICA) is usually associated with vertigo, hearing loss, facial palsy, nystagmus, or truncal ataxia; it is often accompanied by other brainstem or cerebellar signs. Sudden- onset bilateral hearing loss without associated neurological symptoms is infrequent in the literature. We report a case of sudden bilateral hearing loss, later diagnosed as AICA infarction without other symptoms.
Subject(s)
Cerebellum/blood supply , Cerebral Arteries/pathology , Hearing Loss, Bilateral/diagnosis , Hearing Loss, Bilateral/etiology , Aged , Audiometry, Pure-Tone , Brain Ischemia/pathology , Cerebellum/diagnostic imaging , Cerebrovascular Circulation/physiology , Female , Humans , Magnetic Resonance Imaging , Severity of Illness Index , Tomography, X-Ray Computed , Vertigo/diagnosis , Vertigo/etiologyABSTRACT
El infarto isquémico en el territorio de la arteria cerebelosa anteroinferior (AICA) se asocia a vértigo, hipoacusia, parálisis facial, nistagmus o ataxia, suele acompañarse de síntomas neurológicos o cerebelosos y no es infrecuente encontrar afección auditiva concomitante. La hipoacusia bilateral como signo casi único de presentación de infarto cerebeloso es infrecuente y escasamente relatado en la literatura. El caso clínico presentado plantea el diagnóstico de un infarto en el territorio de la AICA, que se inicia como una sordera brusca bilateral
An ischaemic infarction of the anterior inferior cerebellar artery (AICA) is usually associated with vertigo, hearing loss, facial palsy, nystagmus, or truncal ataxia; it is often accompanied by other brainstem or cerebellar signs. Sudden- onset bilateral hearing loss without associated neurological symptoms is infrequent in the literature. We report a case of sudden bilateral hearing loss, later diagnosed as AICA infarction without other symptoms
