Folate-dependent Hypermobility Syndrome: A Proposed Mechanism and Diagnosis

Overview

Journal Heliyon

Specialty Social Sciences

Date 2023 Apr 25

PMID 37095957

Authors

Jacques Courseault

Catherine Kingry

Vivianne Morrison

Christiania Edstrom

Kelli Morrell

Lisa Jaubert

Victoria Elia

Gregory Bix

Affiliations

Soon will be listed here.

Abstract

Hypermobility involves excessive flexibility and systemic manifestations of connective tissue fragility. We propose a folate-dependent hypermobility syndrome model based on clinical observations, and through a review of existing literature, we raise the possibility that hypermobility presentation may be dependent on folate status. In our model, decreased methylenetetrahydrofolate reductase (MTHFR) activity disrupts the regulation of the ECM-specific proteinase matrix metalloproteinase 2 (MMP-2), leading to high levels of MMP-2 and elevated MMP-2-mediated cleavage of the proteoglycan decorin. Cleavage of decorin leads ultimately to extracellular matrix (ECM) disorganization and increased fibrosis. This review aims to describe relationships between folate metabolism and key proteins in the ECM that can further explain the signs and symptoms associated with hypermobility, along with possible treatment with 5-methyltetrahydrofolate supplementation.

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