title: Familial hypertrophic obstructive cardiomyopathy with the GLA E66Q mutation and zebra body.
abstract: BACKGROUND
  Fabry disease is caused by mutations in the α-galactosidase A (GLA) gene, which is located in X-chromosome coding for the lysosomal enzyme of GLA. Among many gene mutations, E66Q mutation is under discussion for its pathogenicity because there is no clinical report showing pathological evidence of Fabry disease with E66Q mutation.
  
  
  METHODS
  A 65-year-old Japanese female was referred to our hospital for chest discomfort on effort. Transthoracic echocardiography showed severe left ventricular (LV) hypertrophy with LV outflow obstruction. Maximum LV outflow pressure gradient was 87 mmHg, and Valsalva maneuver increased the pressure gradient up to 98 mmHg. According to medical interview, one of her younger sister and a nephew died suddenly at age 42 and 36, respectively. Another younger sister also presented LV hypertrophy with outflow obstruction. Maximum LV outflow pressure gradient was 100 mmHg, and the E66Q mutation was detected similar to the case. Endomyocardial biopsy specimens presented vacuolation of cardiomyocytes, in which zebra bodies were detected by electron microscopic examination. Although the enzymatic activity of GLA was within normal range, the c. 196G>C nucleotide change, which lead to the E66Q mutation of GLA gene, was detected. We initially diagnosed her as cardiac Fabry disease based on the findings of zebra body. However, immunostaining showed few deposition of globotriaosylceramide in left ventricular myocardium, and gene mutations in the disease genes for hypertrophic cardiomyopathy (HCM), MYBPC3 and MYH6, were detected. Although the pathogenicity of the E66Q mutation cannot be ruled out, hypertrophic obstructive cardiomyopathy (HOCM) was more reasonable to explain the pathophysiology in the case.
  
  
  CONCLUSIONS
  This is the confusable case of HOCM with Fabry disease with the GLA E66Q mutation. We have to take into consideration the possibility that some patients with the E66Q mutation may have similar histological findings of Fabry disease, and should be examed the possibility for harboring gene mutations associated with HCM.
authors.affiliation: Department of Cardiology and Hematology, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan. moikawa@fmu.ac.jp.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Oikawa
authors.affiliation: Department of Cardiology and Hematology, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sakamoto
authors.affiliation: Department of Cardiology and Hematology, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kobayashi
authors.affiliation: Department of Cardiology and Hematology, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of Cardiology and Hematology, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
authors.forename: Akiomi
authors.initials: A
authors.lastname: Yoshihisa
authors.affiliation: Department of Cardiology and Hematology, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Yamaki
authors.affiliation: Department of Cardiology and Hematology, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakazato
authors.affiliation: Department of Cardiology and Hematology, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Cardiology and Hematology, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
authors.forename: Shu-Ichi
authors.initials: S
authors.lastname: Saitoh
authors.affiliation: Department of Diagnostic Pathology, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
authors.forename: Yuichirou
authors.initials: Y
authors.lastname: Kiko
authors.affiliation: Department of Dermatology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Nakano
authors.affiliation: Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Takeharu
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Kimura
authors.affiliation: Department of Cardiology and Hematology, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
authors.forename: Yasuchika
authors.initials: Y
authors.lastname: Takeishi
mesh_terms: D000368:Aged; D001706:Biopsy; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D004252:DNA Mutational Analysis; D018618:Echocardiography, Doppler, Color; D000795:Fabry Disease / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006801:Humans; D008854:Microscopy, Electron; D009154:Mutation; D032383:Myocytes, Cardiac / Q000737:chemistry / Q000648:ultrastructure*; D010375:Pedigree; D010641:Phenotype; D011237:Predictive Value of Tests; D014281:Trihexosylceramides / Q000032:analysis; D000519:alpha-Galactosidase / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D014281:Trihexosylceramides; C018549:globotriaosylceramide; C576330:GLA protein, human; D000519:alpha-Galactosidase
keywords: E66Q mutation; Fabry disease; Hypertrophic cardiomyopathy; Left ventricular outflow obstruction