title: Clinical and molecular characterization of an extended family with Fabry disease.
abstract: OBJECTIVE
  To characterize clinical manifestations, biochemical changes, mutation of alpha-Galactosidase (alpha-Gal A) gene A (GLA), and functional capability of mutant protein.
  
  
  METHODS
  Seventeen subjects from a family with a newly diagnosed patient with Fabry disease were enrolled in the present study. In each individual, clinical history, physical examination, leukocyte enzyme activity of alpha-Gal A, and mutation analysis were performed. Those with a mutation were further investigated by ophthalmological and audiological evaluations, electrocardiography, echocardiogram, urinalysis, and blood tests to determine renal insufficiency. Expression study of the mutant protein was performed using a Pichia pastoris expression system.
  
  
  RESULTS
  Four affected males and five symptomatic female carriers were identified. Clinical manifestations included severe neuropathic pain, acroparesthesia, hypo-/hyper-hidrosis, frequent syncope, ischemic stroke, cardiac hypertrophy, corneal dystrophy and cart-wheel cataract, high frequency sensorineural hearing loss, periorbital edema and subcutaneous edema over hands and interphalangeal joints. None had angiokeratoma or renal symptoms. The authors identified a novel mutation, p.L106R, in the GLA gene. Recombinant expression of the mutant protein gave little or no enzyme activity compared to the normal protein.
  
  
  CONCLUSIONS
  There were intrafamilial clinical variabilities, but consistent findings of the absence of angiokeratoma and renal symptoms, which could represent a unique feature of this particular mutation.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. radwc@mahidol.ac.th
authors.forename: Duangrurdee
authors.initials: D
authors.lastname: Wattanasirichaigoon
authors.forename: Jisnuson
authors.initials: J
authors.lastname: Svasti
authors.forename: James R Ketudat
authors.initials: JR
authors.lastname: Cairns
authors.forename: Kanchana
authors.initials: K
authors.lastname: Tangnararatchakit
authors.forename: Anannit
authors.initials: A
authors.lastname: Visudtibhan
authors.forename: Siriporn
authors.initials: S
authors.lastname: Keeratichamroen
authors.forename: Lukana
authors.initials: L
authors.lastname: Ngiwsara
authors.forename: Pongsakdi
authors.initials: P
authors.lastname: Khowsathit
authors.forename: Tassanee
authors.initials: T
authors.lastname: Onkoksoong
authors.forename: Apatsa
authors.initials: A
authors.lastname: Lekskul
authors.forename: Dowruang
authors.initials: D
authors.lastname: Mongkolsiri
authors.forename: Chanchai
authors.initials: C
authors.lastname: Jariengprasert
authors.forename: Cheamchit
authors.initials: C
authors.lastname: Thawil
authors.forename: Suwimol
authors.initials: S
authors.lastname: Ruencharoen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D000794:Angiokeratoma / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D000795:Fabry Disease / Q000097:blood / Q000235:genetics* / Q000473:pathology; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D051437:Renal Insufficiency / Q000209:etiology; D000519:alpha-Galactosidase / Q000097:blood / Q000235:genetics*
chemical_list: D000519:alpha-Galactosidase