Biomarkers in Fabry Disease. Implications for Clinical Diagnosis and Follow-up

J Clin Med 2021 Apr 13;10(8):1664. doi: 10.3390/jcm10081664.

PMID: 33924567

Clara Carnicer-Cáceres, Jose Antonio Arranz-Amo, Cristina Cea-Arestin

Highlights: The use of various biomarkers in Fabry disease may help the diagnosis of the disease and the early detection of organ injury, and provide more information on disease progression and prognosis.

Abstract

Background: Deficient alpha-galactosidase A activity in the lysosome due to mutations in the GLA gene causes Fabry disease (FD), a lysosomal storage disorder, which results in gradual accumulation of globotriaosylceramide and other derivatives in different tissues. Substrate accumulation promotes a variety of pathogenic mechanisms including the involvement of several mediators, leading multiorgan lesions, mainly in the kidney, heart and nervous system, resulting in clinical manifestations of the disease. Enzyme replacement therapy has been demonstrated to slow the disease progression, especially when started early. However, a diagnosis in the early stages represents a clinical challenge, especially in patients with a non-classic phenotype, prompting physicians to look for biomarkers that can assist detect and predict disease progression.

Objective: We looked at the mediators involved in several pathogenic pathways that have been investigated as potential biomarkers and can be simply implemented into clinical practice. Some accumulation biomarkers appear to be effective in detecting non-classic forms of the disease, and they may even help with the diagnosis of female patients. The use of a combination of such biomarkers and some response biomarkers for early diagnosis of organ injury could be beneficial. The use of some biomarkers in clinical practice could improve detection capability beyond what is currently available with known diagnostic markers and provide more information on disease progression and prognosis.

Keywords: Gb3, biomarkers, cardiomyopathy, chronic kidney disease, Fabry disease, late-onset phenotype, lyso-Gb3, vasculopathy