The frequency of Fabry disease with the E66Q variant in the ?-galactosidase A gene in Japanese dialysis patients: a case report and a literature review

Kobayashi, Yôko; Sugiyama, Hiroshi; Morinaga, Hiroshi; Inoue, Takashi; Takiue, Keiichi; Kitagawa, M.; Saito, Daiga; Takatori, Yuji; Kinomura, Masaru; Kitamura, Shigehiro; Akagi, Shuji; Sada, Ken‐ei; Nakao, K.; Maeshima, Yoshinori; Kitayama, Hirotsugu; Makino, Hideki

doi:10.5414/cn107097

Cited by 11 publications

(6 citation statements)

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“…More importantly, 2 patients carrying FD (patients 2 and 3) who were over 50 years of age would not have been identified, as well as their relatives. Other studies have also identified FD patients under RRT over 50 years of age [18,33]. These findings raise some concern over whether one should limit the age of performing screening test for FD in male HD patients.…”

Section: Discussionmentioning

confidence: 80%

Targeted Screening of Fabry Disease in Male Hemodialysis Patients in Brazil Highlights Importance of Family Screening

Silva

Barreto

Reis

et al. 2016

Nephron

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Introduction: Fabry disease (FD) is a lysosomal storage disorder caused by enzyme α galactosidase A (α-Gal A) deficiency due to mutations in the galactosidase alpha (GLA) gene. It leads to damage several organs, such as the kidneys, due to progressive accumulation of glycosphingolipids. Objective: To estimate the prevalence of FD among male hemodialysis (HD) patients in a northern state of Brazil. Methods: Screening was performed using a dried blood spot on filter paper to identify patients with low α-Gal A enzyme activity (≤2.2 µmol/l/h). Those with low enzyme activity underwent genetic analysis of the GLA gene. Family screening was conducted in the index cases. Results: 2,583 male HD patients (age: 52 (18-91 years)) were screened. The α-Gal A assay identified 72 males (2.78%) with low enzyme activity. Genotyping identified 3 patients with GLA mutations: W204X, A368T, both previously reported; and C52F, a novel missense mutation. Only the patient with W204X mutation had classic FD. The prevalence rate was 0.12%. Family screening of the index cases identified 23 family members with the same mutations. Conclusions: The prevalence of FD amongst male HD patients found in the Northern of Brazil was low (0.12%). However, family screening of the 3 index cases identified family members at an early stage of the disease, which may benefit from earlier treatment.

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Section: Discussionmentioning

confidence: 80%

Targeted Screening of Fabry Disease in Male Hemodialysis Patients in Brazil Highlights Importance of Family Screening

Silva

Barreto

Reis

et al. 2016

Nephron

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“…Of seven reports on the FD screening of Japanese male dialysis patients, including the two most recent (2,3,6,7,10,28,29), the p.E66Q mutation was found in four studies (3,10,28,29). Thus, the p.E66Q mutation in this population is frequently detected.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the p.E66Q mutation in this population is frequently detected. If we exclude the FD patients with p.E66Q in the previous reports, the prevalence of FD is 0% (10,28,29), 0.2% (6), 0.3% (7), 0.5% (2), and 1.0% (3). The low prevalence of FD in this study was concerned with excluding a patient with FD from study population or a study limitation that not all patients were genotyped, leaving open the possibility that there were some cases of FD missed.…”

Section: Discussionmentioning

confidence: 99%

Screening of Male Dialysis Patients for Fabry Disease by Plasma Globotriaosylsphingosine

Maruyama

Takata²,

Tsubata

et al. 2013

Clinical Journal of the American Society of Nephrology

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Summary Background and objectives Previous reports of Fabry disease screening in dialysis patients indicate that α-galactosidase A activity alone cannot specifically and reliably identify appropriate candidates for genetic testing; a marker for secondary screening is required. Elevated plasma globotriaosylsphingosine is reported to be a hallmark of classic Fabry disease. The purpose of this study was to examine the usefulness of globotriaosylsphingosine as a secondary screening target for Fabry disease. Design, setting, participants, & measurements This study screened 1453 patients, comprising 50% of the male dialysis patients in Niigata Prefecture between July 1, 2010 and July 31, 2011. Screening for Fabry disease was performed by measuring the plasma α-galactosidase A enzyme activity and the globotriaosylsphingosine concentration, by high-performance liquid chromatography. Genetic testing and genetic counseling were provided. Results A low level of plasma α-galactosidase A activity (≤4.0 nmol/h per milliliter) was observed in 47 patients (3.2%). Of these, 3 (0.2%) had detectable globotriaosylsphingosine levels. These patients all had α-galactosidase A gene mutations: one was p.Y173X and two were the nonpathogenic p.E66Q. The patient with p.Y173X started enzyme replacement therapy. Subsequent screening of his family identified the same mutation in his elder sister and her children. Genetic testing for 33 of the other 44 patients detected 7 patients with p.E66Q. Thus, the plasma lyso-Gb3 screen identified Fabry disease with high sensitivity (100%) and specificity (94.3%). Conclusions Plasma globotriaosylsphingosine is a promising secondary screening target that was effective for selecting candidates for genetic counseling and testing and for uncovering unrecognized Fabry disease cases.

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“…There are reports on the frequency of Fabry diseaseinduced dialysis patients, but these were not necessarily examined using a sufficient number of dialysis patients [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. With respect to the clinical diagnosis of ESKD in dialysis patients, the frequency of diabetic nephropathy, chronic glomerulonephritis, nephrosclerosis, etc., is high; however, cases in which the clinical diagnosis of ESKD is unknown are also frequent at about 7.8 % in Japan [24].…”

Section: Introductionmentioning

confidence: 99%

Prevalence of Fabry disease in dialysis patients: Japan Fabry disease screening study (J-FAST)

et al. 2015

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The frequency of Fabry disease with the E66Q variant in the ?-galactosidase A gene in Japanese dialysis patients: a case report and a literature review

Cited by 11 publications

References 0 publications

Targeted Screening of Fabry Disease in Male Hemodialysis Patients in Brazil Highlights Importance of Family Screening

Targeted Screening of Fabry Disease in Male Hemodialysis Patients in Brazil Highlights Importance of Family Screening

Screening of Male Dialysis Patients for Fabry Disease by Plasma Globotriaosylsphingosine

Prevalence of Fabry disease in dialysis patients: Japan Fabry disease screening study (J-FAST)

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