title: A family with various symptomatology suggestive of Anderson-Fabry disease and a genetic polymorphism of alpha galactosidase A gene.
abstract: BACKGROUND
  Anderson/Fabry disease expresses a wide range of clinical variability in patients that it is possible to explain referring to a genetic variability with numerous mutations described in the literature (more than 600).
  
  
  METHODS
  We report some clinical cases of some members of a Sicilian family to express phenotypical variability of this disease in subjects with the same genetic mutation
  
  
  RESULTS
  The first case was a 59-year-old female. Brain MRI revealed right frontal periventricular white matter of likely vascular-degenerative origin. The proband's alpha galactosidase A activity was 3.7nmol/mL/h. Molecular genetics revealed a polymorphism: -10 C>T; IVS 2-76_80del5; IVS4-16 A>G; IVS6-22 C>T. The second case was a 30year-old male affected by acroparesthesias and hypoidrosis since he was an adolescent. Renal impairment was first detected at age 29; it began with high plasma levels of creatinine and microalbuminuria date. The third case was a 41year-old daughter that presented with acroparesthesias, hypoidrosis since she was very young. The patient's alpha galactosidase A activity was 4.1nmol/mL/h, in whole blood, which is compatible with heterozygote subject for Fabry's disease or healthy control. The fourth case was a male grandson of the proband, 9year-old child. He had a classic gastrointestinal involvement. He complained of recurrent abdominal pain, post prandial bloating and pain. This child's enzyme activity was 1.65nmol/mL/h. In cases 2, 3, and 4, molecular genetics revealed a polymorphism: -10 C>T; IVS 2-76_80del5; IVS4-16 A>G; IVS6-22 C<T DISCUSSION: A recent study reported that IVS4+68 A>G, IVS6-22C>T polymorphisms occurred in 8.9% and 3.7% of the subjects respectively, and the significance of this haplotype in FD pathology remains unknown but possibly suggestive of Anderson/Fabry disease.
authors.affiliation: U.O.C di Medicina Interna e CardioAngiologia, Dipartimento Biomedico di Medicina Interna e Specialistica, Università degli Studi di Palermo, Pzza delle Cliniche, n.2, 90127 Palermo, Italy. Electronic address: bruno.tuttolomondo@unipa.it.
authors.forename: Antonino
authors.initials: A
authors.lastname: Tuttolomondo
authors.affiliation: CNR-IBIM: Institute of Biomedicine and Molecular Immunology "A. Monroy" Palermo, Via Ugo la Malfa n.153, 90146 Palermo, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Duro
authors.affiliation: U.O.C di Medicina Interna e CardioAngiologia, Dipartimento Biomedico di Medicina Interna e Specialistica, Università degli Studi di Palermo, Pzza delle Cliniche, n.2, 90127 Palermo, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Pecoraro
authors.affiliation: U.O.C di Medicina Interna e CardioAngiologia, Dipartimento Biomedico di Medicina Interna e Specialistica, Università degli Studi di Palermo, Pzza delle Cliniche, n.2, 90127 Palermo, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Simonetta
authors.affiliation: U.O.C di Medicina Interna e CardioAngiologia, Dipartimento Biomedico di Medicina Interna e Specialistica, Università degli Studi di Palermo, Pzza delle Cliniche, n.2, 90127 Palermo, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Miceli
authors.affiliation: CNR-IBIM: Institute of Biomedicine and Molecular Immunology "A. Monroy" Palermo, Via Ugo la Malfa n.153, 90146 Palermo, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Colomba
authors.affiliation: CNR-IBIM: Institute of Biomedicine and Molecular Immunology "A. Monroy" Palermo, Via Ugo la Malfa n.153, 90146 Palermo, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Zizzo
authors.affiliation: U.O.C di Medicina Interna e CardioAngiologia, Dipartimento Biomedico di Medicina Interna e Specialistica, Università degli Studi di Palermo, Pzza delle Cliniche, n.2, 90127 Palermo, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Di Chiara
authors.affiliation: U.O.C di Medicina Interna e CardioAngiologia, Dipartimento Biomedico di Medicina Interna e Specialistica, Università degli Studi di Palermo, Pzza delle Cliniche, n.2, 90127 Palermo, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Scaglione
authors.affiliation: U.O.C di Medicina Interna e CardioAngiologia, Dipartimento Biomedico di Medicina Interna e Specialistica, Università degli Studi di Palermo, Pzza delle Cliniche, n.2, 90127 Palermo, Italy.
authors.forename: Vittoriano
authors.initials: V
authors.lastname: Della Corte
authors.affiliation: U.O.C di Medicina Interna e CardioAngiologia, Dipartimento Biomedico di Medicina Interna e Specialistica, Università degli Studi di Palermo, Pzza delle Cliniche, n.2, 90127 Palermo, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Corpora
authors.affiliation: U.O.C di Medicina Interna e CardioAngiologia, Dipartimento Biomedico di Medicina Interna e Specialistica, Università degli Studi di Palermo, Pzza delle Cliniche, n.2, 90127 Palermo, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pinto
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D000795:Fabry Disease / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009691:Nucleic Acid Denaturation; D010375:Pedigree; D011110:Polymorphism, Genetic; D000519:alpha-Galactosidase / Q000235:genetics*
chemical_list: D000519:alpha-Galactosidase
keywords: Anderson–Fabry disease; Haplotype; Symptomatology