The Ehlers-Danlos Syndromes (EDS) are a group of heritable disorders of connective tissue with joint hypermobility, chronic pain and a wide range of co-morbid conditions. There is considerable overlap with the phenotype of hypophosphatasia (HPP) (Whyte, 1994, 2012; Szabo et al.,2019), including the musculoskeletal system, respiratory system, dental and neurologic issues. Preliminary search through the EMR of two hospital systems and one private medical practice has found that about 7-8% of patients with an EDS diagnosis have a low alkaline phosphatase level.
2.2 Rationale and Study Significance
The current diagnostic criteria for the Ehlers-Danlos syndromes (EDS) were published in 2017 (Mailfait et al., 2017). Also published in 2017 was a document describing a new way of thinking about hypermobility, defining the hypermobility spectrum disorders (HSD) (Castori et al., 2017).
The Ehlers-Danlos syndromes present with a clinical findings that overlap significantly with the clinical presentation of hypophosphatasia. Both groups have joint hypermobility, fatigue (Hakim et al., 2017) and chronic joint pain (Chopra et al., 2017), muscle weakness, delayed motor function, and may present with low bone density. Chiari malformation (Henderson et al., 2017) is also seen in both groups.
Preliminary studies in three geographic locations have found that approximately 7-8% of large populations with a diagnosis of EDS have at least one low alkaline phosphatase level. We are therefore interested in establishing the clinical overlap between these two diagnostic entities, as well as patients who in fact have HPP and were misdiagnosed with EDS. We will be looking closely at the phenotypes to determine whether these are co-morbid conditions or represent a sub-group within the EDS or HPP populations. We are also interested in exploring treatment options for persons with EDS and meeting the criteria for HPP, once the phenotypes have been delineated.
2.3 Potential Risks and Benefits
We hypothesize: (1) there is a subset of patients, previously diagnosed with EDS, who in fact have HPP. These patients would be diagnosed with HPP and would benefit from treatment for HPP (Whyte et al, 2012). (2) there is a subset of patients with EDS with low alkaline phosphatase that represents a distinct phenotype with overlap between EDS and HPP. These patients may benefit from treatment as well.
2.3.2 Known Potential Benefits
There is currently no medication that is a specific treatment for EDS. By being able to further delineate these EDS patients in to the aforementioned subgroups there is a potential for medication treatment previously not accessible to EDS patients.
HPP is considered a rare and orphan disease. By studying these groups together more HPP patients can potentially be picked up and thus potentially benefit from treatment and improvement of quality of life.
