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

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, ?-galactosidase A (?-Gal A) activity, and analysis of the ?-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 ?-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 ?-Gal A activity (5 with GLA mutations; 4 classic and 1 late-onset) and 7 exhibited normal ?-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.

SUBMITTER: Maruyama H

PROVIDER: S-EPMC6363642 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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

Maruyama Hiroki H Miyata Kaori K Mikame Mariko M Taguchi Atsumi A Guili Chu C Shimura Masaru M Murayama Kei K Inoue Takeshi T Yamamoto Saori S Sugimura Koichiro K Tamita Koichi K Kawasaki Toshihiro T Kajihara Jun J Onishi Akifumi A Sugiyama Hitoshi H Sakai Teiko T Murata Ichijiro I Oda Takamasa T Toyoda Shigeru S Hanawa Kenichiro K Fujimura Takeo T Ura Shigehisa S Matsumura Mimiko M Takano Hideki H Yamashita Satoshi S Matsukura Gaku G Tazawa Ryushi R Shiga Tsuyoshi T Ebato Mio M Satoh Hiroshi H Ishii Satoshi S

Genetics in medicine : official journal of the American College of Medical Genetics 20180315 1

<h4>Purpose</h4>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.<h4>Methods</h4>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 di ...[more]

PMID: 29543226

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Project description:Biomarkers useful for diagnosis and evaluation of treatment for patients with Fabry disease are urgently needed. Recently, plasma globotriaosylsphingosine (lyso-Gb3) and lyso-Gb3-related analogues have attracted attention as promising biomarkers of Fabry disease. However, the plasma concentrations of lyso-Gb3 and its analogues are extremely low or below the detection limits in some Fabry patients as well as in healthy subjects. In this paper, we introduce the novel application of a nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) system to the measurement of lyso-Gb3 and its analogues in plasma. Nano-LC-MS/MS requires smaller amounts of samples and is more sensitive than conventional techniques. Using this method, we measured the plasma concentrations of lyso-Gb3 and its analogues in 40 healthy subjects, 5 functional variants (males with E66Q), and various Fabry patients (9 classic Fabry males/9 mutations; 7 later-onset Fabry males/5 mutations; and 10 Fabry females/9 mutations). The results revealed that the mean lyso-Gb3 and lyso-Gb3(-2) concentrations in all the Fabry patient subgroups were statistically higher, especially in the classic Fabry males, than those in the functional variants and healthy subjects. The plasma concentrations of lyso-Gb3 and its analogues in healthy subjects, functional variants, and some Fabry patients with specific mutations (R112H and M296I) that cannot be established by conventional techniques were successfully determined by means of nano-LC-MS/MS. The lyso-Gb3 and lyso-Gb3(-2) concentrations in male patients with these mutations were lower than those in most Fabry patients having other mutations, but higher than those in the functional variants and healthy subjects. This new method is expected to be useful for sensitive determination of the plasma concentrations of lyso-Gb3 and its analogues. This study also revealed that not only lyso-Gb3 but also lyso-Gb3(-2) in plasma is a useful biomarker for the diagnosis of Fabry disease.

Dataset Information

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

Publications

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

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