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Published on: December 20, 2017
Plasma lyso-Gb3: a biomarker for monitoring fabry patients during enzyme replacement therapy
Hitoshi Sakuraba1, Tadayasu Togawa2, Takahiro Tsukimura2
1Department of Clinical Genetics, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo, 204-8588, Japan. sakuraba@my-pharm.ac.jp.
Background:
Recently, globotriaosylsphingosine (lyso-Gb3) has attracted interest as a biomarker of Fabry disease. However, little is known regarding its utility for the evaluation of the therapeutic efficacy.
Method:
We measured plasma lyso-Gb3 concentration in Japanese healthy subjects and Fabry patients by means of liquid chromatography-tandem mass spectrometry (LC-MS/MS). We determined the reference interval in Japanese (UMIN000016854), and examined the effect of enzyme replacement therapy (ERT) with recombinant α-galactosidase A (GLA) and the influence of antibodies against the enzyme on the plasma lyso-Gb3 level in Fabry patients (UMIN000017152).
Results:
The reference interval was determined to be 0.35-0.71 nmol/L, this being almost the same as the normal range in a non-Japanese population previously reported. The analysis revealed that the plasma lyso-Gb3 level was strikingly increased in classic Fabry males, and to a lesser extent in later-onset Fabry males and Fabry females. The elevation of the plasma lyso-Gb3 level was related to renal involvement in the Fabry females. ERT gave a rapid reduction in the elevated plasma lyso-Gb3 level in the classic Fabry males, and a gradual one or stabilization in most of the later-onset Fabry males and Fabry females. However, formation of antibodies against the recombinant GLA had a negative effect on the reduction of plasma lyso-Gb3.
Conclusions:
Regular observation of plasma lyso-Gb3 and antibodies is useful for monitoring of Fabry patients during ERT.
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