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Genet Med. 2019 Jan;21(1):44-52. doi: 10.1038/gim.2018.31. Epub 2018 Mar 15.

Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis.

Author information

1
Department of Clinical Nephroscience, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. hirokim@med.niigata-u.ac.jp.
2
Sanofi K.K., Sanofi Genzyme Medical Operations, Rare Disease Medical, Medical Science Liaison, Tokyo, Japan.
3
Department of Clinical Nephroscience, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
4
Department of Metabolism, Chiba Children's Hospital, Chiba, Japan.
5
Department of Pediatrics, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan.
6
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
7
Nishinomiya Watanabe Cardiovascular Center, Nishinomiya, Japan.
8
Department of Cardiology, Fujinomiya City General Hospital, Fujinomiya, Japan.
9
Department of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan.
10
Sukoyaka Clinic, Gifu, Japan.
11
Department of Chronic Kidney Disease, Gifu University Graduate School of Medicine, Gifu, Japan.
12
Yamaguchi Prefectural Grand Medical Center, Hofu, Japan.
13
Department of Cardiovascular Medicine, Dokkyo Medical University, Mibu, Japan.
14
Department of Cardiology, Internal Medicine, Iwaki Kyoritsu General Hospital, Iwaki, Japan.
15
Department of Nephrology, Kashiwazaki General Hospital and Medical Center, Kashiwazaki, Japan.
16
Division of Neurology, Japanese Red Cross Asahikawa Hospital, Asahikawa, Japan.
17
Department of Nephrology, Tokyo Teishin Hospital, Kashiwazaki, Japan.
18
Department of Cardiology, Japanese Red Cross Hamamatsu Hospital, Hamamatsu, Japan.
19
Division of Medical Genetics, Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, Niigata, Japan.
20
Department of Cardiology, Tokyo Women's Medical University, Tokyo, Japan.
21
Division of Cardiology, Showa University Fujigaoka Hospital, Yokohama, Japan.
22
Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine, Hamamatsu, Japan.
23
GlycoPharma Corporation, Oita, Japan.

Abstract

PURPOSE:

Plasma globotriaosylsphingosine (lyso-Gb3) is a promising secondary screening biomarker for Fabry disease. Here, we examined its applicability as a primary screening biomarker for classic and late-onset Fabry disease in males and females.

METHODS:

Between 1 July 2014 and 31 December 2015, we screened 2,359 patients (1,324 males) referred from 168 Japanese specialty clinics (cardiology, nephrology, neurology, and pediatrics), based on clinical symptoms suggestive of Fabry disease. We used the plasma lyso-Gb3 concentration, α-galactosidase A (α-Gal A) activity, and analysis of the α-Gal A gene (GLA) for primary and secondary screens, respectively.

RESULTS:

Of 8 males with elevated lyso-Gb3 levels (≥2.0 ng ml-1) and low α-Gal A activity (≤4.0 nmol h-1 ml-1), 7 presented a GLA mutation (2 classic and 5 late-onset). Of 14 females with elevated lyso-Gb3, 7 displayed low α-Gal A activity (5 with GLA mutations; 4 classic and 1 late-onset) and 7 exhibited normal α-Gal A activity (1 with a classic GLA mutation and 3 with genetic variants of uncertain significance).

CONCLUSION:

Plasma lyso-Gb3 is a potential primary screening biomarker for classic and late-onset Fabry disease probands.

KEYWORDS:

Fabry disease; gene analysis; genetic variants of uncertain significance; lyso-Gb3; screening

PMID:
29543226
PMCID:
PMC6363642
DOI:
10.1038/gim.2018.31
[Indexed for MEDLINE]
Free PMC Article

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