Folate-dependent hypermobility syndrome: A proposed mechanism and diagnosis
Jacques Courseault,
Catherine Kingry,
Vivianne Morrison,
Christiania Edstrom,
Kelli Morrell,
Lisa Jaubert,
Victoria Elia,
Gregory Bix
Affiliations
Jacques Courseault
Tulane University School of Medicine, Department of Orthopedics, The Fascia Institute and Treatment Center 7030 Canal Blvd, New Orleans, LA 70124, USA; Corresponding
Catherine Kingry
Tulane University School of Medicine, Department of Orthopedics, The Fascia Institute and Treatment Center 7030 Canal Blvd, New Orleans, LA 70124, USA
Vivianne Morrison
Tulane University School of Medicine, Departments of Neurosurgery and Neurology, Clinical Neuroscience Research Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA
Christiania Edstrom
Tulane University School of Medicine, Department of Orthopedics, The Fascia Institute and Treatment Center 7030 Canal Blvd, New Orleans, LA 70124, USA
Kelli Morrell
Tulane University School of Medicine, Department of Orthopedics, The Fascia Institute and Treatment Center 7030 Canal Blvd, New Orleans, LA 70124, USA
Lisa Jaubert
Tulane University School of Medicine, Department of Orthopedics, The Fascia Institute and Treatment Center 7030 Canal Blvd, New Orleans, LA 70124, USA
Victoria Elia
Tulane University School of Medicine, Department of Orthopedics, The Fascia Institute and Treatment Center 7030 Canal Blvd, New Orleans, LA 70124, USA
Gregory Bix
Tulane University School of Medicine, Departments of Neurosurgery and Neurology, Clinical Neuroscience Research Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA; Corresponding
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.
