title: Organ manifestations and long-term outcome of Fabry disease in patients with the GLA haplotype D313Y.
abstract: OBJECTIVE
  The severity of Fabry disease is dependent on the type of mutation in the α-galactosidase A (AgalA) encoding gene (GLA). This study focused on the impact of the GLA haplotype D313Y on long-term organ involvement and function.
  
  
  METHODS
  In this monocentric study, all participants presenting with the D313Y haplotype between 2001 and 2015 were comprehensively clinically investigated at baseline and during a 4-year follow-up if available. Five females and one male were included.
  
  
  METHODS
  Cardiac, nephrological, neurological, laboratory and quality of life data.
  
  
  RESULTS
  AgalA enzyme activity in leucocytes (0.3±0.9 nmol/min/mg protein (mean±SD)) and serum lyso-Gb3 (0.6±0.3 ng/mL at baseline) were in normal range in all patients. Cardiac morphology and function were normal (left-ventricular (LV) ejection fraction 66±8%; interventricular septum 7.7±1.4 mm; LV posterior wall 7.5±1.4 mm; normalised LV mass in MRI 52±9 g/m(2); LV global longitudinal strain -21.6±1.9%) and there were no signs of myocardial fibrosis in cardiac MRI. Cardiospecific biomarkers were also in normal range. Renal function was not impaired (estimated glomerular filtration rate MDRD 103±15 mL/min; serum-creatinine 0.75±0.07 mg/dL; cystatin-c 0.71±0.12 mg/L). One female patient (also carrying a Factor V Leiden mutation) had a transitory ischaemic attack. One patient showed white matter lesions in brain MRI, but none had Fabry-associated pain attacks, pain crises, evoked pain or permanent pain. Health-related quality of life analysis revealed a reduction in individual well-being. At long-term follow-up after 4 years, no significant change was seen in any parameter.
  
  
  CONCLUSIONS
  The results of the current study suggest that the D313Y genotype does not lead to severe organ manifestations as seen in genotypes known to be causal for classical FD.
authors.affiliation: Department of Internal Medicine I and Comprehensive Heart Failure Center (CHFC), University Hospital Würzburg, Würzburg, Germany Fabry Center for Interdisciplinary Therapy (FAZIT), University Hospital Würzburg, Würzburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Oder
authors.affiliation: Fabry Center for Interdisciplinary Therapy (FAZIT), University Hospital Würzburg, Würzburg, Germany Department of Neurology, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Nurcan
authors.initials: N
authors.lastname: Üçeyler
authors.affiliation: Department of Internal Medicine I and Comprehensive Heart Failure Center (CHFC), University Hospital Würzburg, Würzburg, Germany.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Internal Medicine I and Comprehensive Heart Failure Center (CHFC), University Hospital Würzburg, Würzburg, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Hu
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Petritsch
authors.affiliation: Fabry Center for Interdisciplinary Therapy (FAZIT), University Hospital Würzburg, Würzburg, Germany Department of Neurology, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sommer
authors.affiliation: Department of Internal Medicine I and Comprehensive Heart Failure Center (CHFC), University Hospital Würzburg, Würzburg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Ertl
authors.affiliation: Department of Internal Medicine I and Comprehensive Heart Failure Center (CHFC), University Hospital Würzburg, Würzburg, Germany Fabry Center for Interdisciplinary Therapy (FAZIT), University Hospital Würzburg, Würzburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanner
authors.affiliation: Department of Internal Medicine I and Comprehensive Heart Failure Center (CHFC), University Hospital Würzburg, Würzburg, Germany Fabry Center for Interdisciplinary Therapy (FAZIT), University Hospital Würzburg, Würzburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Nordbeck
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D015716:Electrocardiography, Ambulatory; D005080:Exercise Test; D000795:Fabry Disease / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D006017:Glycolipids / Q000097:blood*; D006239:Haplotypes; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011788:Quality of Life; D013107:Sphingolipids / Q000097:blood*; D016277:Ventricular Function, Left; D055815:Young Adult; D000519:alpha-Galactosidase / Q000235:genetics*
chemical_list: D015415:Biomarkers; D006017:Glycolipids; D013107:Sphingolipids; C063288:globotriaosyl lysosphingolipid; C576330:GLA protein, human; D000519:alpha-Galactosidase
keywords: Anderson-Fabry Disease; D313Y genotype; Fabry cardiomyopathy; Fabry nephropathy; Fabry-associated pain; Inherited metabolic disorders