Scientists have learned more about the genetic factors that may underlie double-jointedness, also known as hypermobility, and diseases that affect connective tissue called hypermobile Ehlers-Danlos syndrome (EDS). There are thirteen subtypes of EDS, and hypermobile EDS makes up 90 percent of cases. It's not unusual for people to have overly flexible joints; maybe they can easily do a split, or bend their thumb back to their wrist or beyond. But hypermobility can also indicate a far more serious condition.
Hypermobile EDS can cause the connective tissue in joints to be fragile. It can also lead to other issues like chronic fatigue, dizziness, joint pain, thin tooth enamel, digestive trouble, migraines, and some psychiatric disorders like anxiety or depression. The risk of endometriosis or uterine fibroids may also increase in women with hypermobile EDS. The causes of the disorder have been unclear, however, and treatment usually only addresses the symptoms.
Hypermobile EDS has been the only type of EDS for which genetic influences have not been identified, until this study, which was reported in the journal Heliyon. In this work, the investigators connected hypermobility and hypermobile EDS to folate deficiency caused by a variant of a gene called MTHFR.
Small variations in the sequences of various genes can have a wide range of impacts. In some cases, variants may have no obvious effect while in others, they can lead to a serious disorder. In this case, people with a specific variation in their MTHFR gene are not able to metabolize folate, or vitamin B9. Unmetabolized folate builds up in the bloodstream, and the lack of folate in the body could be preventing crucial proteins from linking collagen to the extracellular matrix; this can lead to connective tissue in joints that is highly elastic, hypermobility, and other issues.
The Beighton score has been used to diagnose hypermobility, and there are some doubts about how well it works. The number of people with hypermobility is unknown, but the study authors suggested that as many as half of the people in the world may have this condition and many may not know.
"You've got millions of people that likely have this, and until now, there's been no known cause we've known to treat," said Dr. Gregory Bix, director of the Tulane University Clinical Neuroscience Research Center. "It's a big deal."
"Hypermobility is widespread and unfortunately under-recognized," said Dr. Jacques Courseault, medical director of the Tulane Fascia Institute and Treatment Center. "I'm excited about being able to treat the masses where people aren't going their whole lives being frustrated and not getting the treatment they need."
"Hypermobility is not rare," Courseault added. "Hypermobility is like a Ferrari that requires a lot of maintenance and the best synthetic oil. After knowing a patient's name and date of birth, I think it's prudent for clinicians to know which of these body types they have."
Research has indicated that in hypermobility patients who also have other symptoms that are potentially related, unmetabolized folate levels are abnormally high. Most people who have these elevated folate serum levels also carried the genetic variant.
There is also a potential treatment that is already available. Methylated folate, which basically pre-metabolized folate, has already been approved by the FDA and is widely available.
Although the study authors cautioned that more research has to be done, folate has already improved symptoms in some patients who have been treated.
Sources: Tulane University, Heliyon
