title: Comprehensive clinical evaluation of a large Spanish family with Anderson-Fabry disease, novel GLA mutation and severe cardiac phenotype.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Servicio de Medicina Interna, Hospital Clínico Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain. Electronic address: irene.sanroman@gmail.com.
authors.forename: Irene
authors.initials: I
authors.lastname: San Román-Monserrat
authors.affiliation: Servicio de Cardiología, Hospital Clínico Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Moreno-Flores
authors.affiliation: Servicio de Cardiología, Hospital Clínico Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain.
authors.forename: David
authors.initials: D
authors.lastname: López-Cuenca
authors.affiliation: Servicio de Oftalmología, Hospital Clínico Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Rodríguez-González-Herrero
authors.affiliation: Unidad de Genética Médica, Servicio de Pediatría, Hospital Clínico Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain; Cátedra de Genética Médica, Universidad Católica San Antonio de Murcia, Spain; Grupo Clínico Vinculado al Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
authors.forename: Encarna
authors.initials: E
authors.lastname: Guillén-Navarro
authors.affiliation: Servicio de Otorrinolaringología, Hospital Clínico Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Rodríguez-González-Herrero
authors.affiliation: Servicio de Nefrología, Hospital Clínico Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain.
authors.forename: Marisol
authors.initials: M
authors.lastname: Alegría-Fernández
authors.affiliation: Servicio de Medicina Interna, Hospital Clínico Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Poza-Cisneros
authors.affiliation: Sección de Nefrología Pediátrica, Hospital Clínico Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Piñero-Fernández
authors.affiliation: Servicio de Oftalmología, Hospital Clínico Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Sornichero-Martínez
authors.affiliation: Servicio de Cardiología, Hospital Clínico Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain; Facultad de Medicina, Universidad de Murcia, Spain.
authors.forename: Juan R
authors.initials: JR
authors.lastname: Gimeno-Blanes
mesh_terms: D000328:Adult; D017668:Age of Onset; D019943:Amino Acid Substitution; D001145:Arrhythmias, Cardiac / Q000209:etiology; D001921:Brain / Q000473:pathology; D056947:Enzyme Replacement Therapy; D005128:Eye Diseases / Q000209:etiology; D000795:Fabry Disease / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology; D005260:Female; D005838:Genotype; D006323:Heart Arrest / Q000209:etiology; D016027:Heart Transplantation; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000209:etiology; D007668:Kidney / Q000473:pathology; D052177:Kidney Diseases, Cystic / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000601:surgery; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009206:Myocardium / Q000473:pathology; D010375:Pedigree; D017354:Point Mutation; D013030:Spain / Q000453:epidemiology; D000519:alpha-Galactosidase / Q000235:genetics* / Q000627:therapeutic use
chemical_list: C576330:GLA protein, human; D000519:alpha-Galactosidase
keywords: Fabry; Female; Gravedad; Mujer; Multidisciplinar; Multidisciplinary; Mutación; Mutation; Severity