High-risk screening for Anderson–Fabry disease in patients with cardiac, renal, or neurological manifestations


Anderson–Fabry disease (AFD) is an X-linked lysosomal storage disorder caused by abnormalities in the α-galactosidase (Gal) A gene (GLA; MIM:300644). The reduced activity of the lysosomal enzyme, α-galactosidase A (α-Gal A) leads to classic early manifestations and vascular disease of the heart, kidneys, and brain. As a high-risk screening for symptomatic AFD using an enzymatic assay on dried blood spot samples, we enrolled 2325 individuals (803 females and 1522 males; median age: 66 years) with cardiac, renal, or neurological manifestations that met at least one of the following criteria: (a) family history of early-onset cardiovascular diseases; (b) typical classic manifestations, such as acroparesthesias, clustered angiokeratoma, cornea verticillata, and hypo-anhidrosis; (c) proteinuria; (d) receiving dialysis; (e) left ventricular hypertrophy on electrocardiography or echocardiography; or (f) history of stroke. Ninety-two patients displayed low α-Gal A activity. Four males and two females had different pathogenic GLA mutations (0.26%) including a novel mutation c.908-928del21. Four males (0.17%) harbored the GLA c.196G>C (p.E66Q) variant. This simple screening protocol using dried blood spot samples is useful for early diagnosis of AFD in high-risk and underdiagnosed patients suffering from various cardiac, renal, or neurological manifestations.

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We thank Professor Yoshio Makita of Asahikawa Medical University for the genetic counseling and Kaori Kanno of Asahikawa Medical University, Fumiko Nozaki, Naomi Yano, and Matsumi Harada of Kumamoto University for their excellent technical assistance. In addition to the authors, the following investigators and institutions participated in this study: H.N. Medic Sapporo-Higashi (Masataka Tsunoda); H.N. Medic Sapporo (Nobuo Hashimoto); H.N. Medic Kitahiroshima (Ryota Ikee); Kitasaito Hospital (Atsushi Wada, Tomoya Hirayama); Nagayama Kidney and Urology Clinic (Mitsuhiro Mizunaga); Jinyukai Hospital (Kazuyuki Maeno); Tomakomai Nissho Hospital (Kazuya Sakamoto); Hokkaido Kitami Hospital (Kazumi Uekita); Hokkaido Haboro Hospital (Tomoya Koizumi, Wataru Sasao); Abashiri Kosei Hospital (Toshihiro Hirai, Hideki Nakamura); Teine Keijinkai Hospital (Takuto Maeda, Hideki Takizawa); Teine Inazumi Hospital (Susumu Saito); Engaru Kosei Hospital (Kanako Matsuda, Motoi Kijima); Uno Clinic (Motohiro Uno); Kushiro City General Hospital (Ken Morita); Kushiro Red Cross Hospital (Junya Yamamoto); NTT East Sapporo Hospital (Tomochika Maoka); KKR Sapporo Medical Center (Hirofumi Kon); Ebetsu City Hospital (Masahiko Abe); Municipal Ashibetsu Hospital (Yasuhiro Nakamura); Hokkaido Cardiovascular Hospital (Yusuke Kashiwagi); Sawamura Dialysis Clinic (Naruhiko Tanaka); National Hospital Organization Hokkaido Medical Center (Takashi Takenaka); National Hospital Organization Obihiro Hospital (Mayumi Aoki, Hiromi Obata); Hakodate Watanabe Hospital (Hisanobu Ota); Asahikawa Kosei Hospital (Atsushi Yamauchi); National Hospital Organization Asahikawa Medical Center (Yoko Aburakawa); Nayoro City General Hospital (Sarasa Toyoshima); Sapporo Rouaikai Hospital (Hidenori Furui); Nissei Hospital (Hiromitsu Yoshie); Hokusei Hospital (Eriko Yamagishi); Iwamizawa Municipal General Hospital (Yoshiaki Aizawa); Megumino Hospital (Yasutaka Hirayama); Ohkawara Neurosurgical Hospital (Noriaki Shojima); Iburi Urological Clinic (Masashi Bandou, Yutaka Takeuchi); Hakodate Goryoukaku Hospital (Fumio Obara); Hakodate Municipal Hospital (Misuzu Osaka); Kitamihara clinic (Sugako Akihama); Chitose City Hospital (Tomoko Sakai); and Ido Medical Clinic (Akira Ido).

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Correspondence to Naoki Nakagawa.

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Nakagawa, N., Sawada, J., Sakamoto, N. et al. High-risk screening for Anderson–Fabry disease in patients with cardiac, renal, or neurological manifestations. J Hum Genet 64, 891–898 (2019). https://doi.org/10.1038/s10038-019-0633-1

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