How well does urinary lyso-Gb3 function as a biomarker in Fabry disease?

Area of Science:

• Biochemistry
• Genetics
• Clinical Diagnostics

Background:

• Fabry disease involves glycosphingolipid accumulation, notably globotriaosylceramide (Gb(3)).
• Globotriaosylsphingosine (lyso-Gb(3)) is an elevated plasma biomarker in Fabry disease.
• Urinary lyso-Gb(3) was previously undetectable due to interfering substances.

Purpose of the Study:

• To characterize urinary lyso-Gb(3).
• To develop a mass spectrometry method for quantifying urinary lyso-Gb(3).
• To evaluate urinary lyso-Gb(3) as a Fabry disease biomarker.

Main Methods:

• Analysis of urinary lyso-Gb(3) in 83 Fabry patients and 77 controls.
• Development of a mass spectrometry-based quantification method.
• Assessment of lyso-Gb(3) inhibition of alpha-galactosidase A activity.

Main Results:

• The developed method demonstrated high precision (<15% bias).
• Urinary lyso-Gb(3) levels correlated with Gb(3) concentrations, mutation type, gender, and treatment status.
• No detectable lyso-Gb(3) was found in healthy controls; it did not inhibit GLA activity.

Conclusions:

• Urinary lyso-Gb(3) is a reliable and independent biomarker for Fabry disease.
• Elevated urinary lyso-Gb(3) correlates with key indicators of disease severity.
• This biomarker aids in assessing clinically important characteristics of Fabry disease.