HPP and Ehlers-Danlos Syndrome: Clinical Investigation
Clair Francomano
Primary Investigator
Brief description of study
What is the purpose of this study?
The Ehlers-Danlos Syndromes (EDS) are a group of heritable disorders of connective tissue with joint hypermobility, chronic pain and a wide range of other conditions that overlap in symptoms including the musculoskeletal system, respiratory system, dental and neurologic issues. We think there may be a subset of patients, previously diagnosed with EDS, who in fact have hypophosphatasia (HPP). These patients would benefit from treatment for HPP which exists. We also think there might be a subset of patients with EDS with low alkaline phosphatase that represents a distinct subtype with overlap between EDS and HPP. These patients may benefit from treatment as well.
Detailed description of study
What will happen during the study?
As part of their clinical care, subjects will be assessed for a second alkaline phosphatase and will need to get approximately 3mL of blood drawn to assess alkaline phosphatase, Vitamin B6 and Zinc levels. We will access these test results from the subjects’ medical records. Those with two low alkaline phosphatase levels will undergo genetic testing for HPP. We hope to identify a total of 60 patients to define the phenotype. We plan to recruit 30 participants who do not have a second low alkaline phosphatase level and 30 participants who do. In both cohorts we will assess the presence or absence and degree of severity of specific clinical features, including but not limited to pain, skeletal deformities, low-trauma fractures, premature loss of primary teeth, history of rickets, dental abnormalities, short stature, osteomalacia, impaired mobility, gait disturbance, joint hypermobility, muscle weakness, fatigue, CRPS (chronic regional pain syndromes), hypercalcemia, nephrocalcinosis, ophthalmic calcification of the cornea and conjunctiva, and elevated phosphate levels, postural orthostatic tachycardia syndrome (POTS), mast cell activation disorders (MCAD), Chiari I malformation and cranio- cervical instability, and nutritional deficiencies.
Subjects will be required to also participate in the Musculoskeletal Function, Imaging and Tissue Resource Core (FIT) Core study, IRB number 170755085. A separate informed consent will be collected for participation in the (FIT) Core. Data from The FIT Core study procedures will be collected and used for purposes of participation in this study.
This information will be collected in 3 ways, 1) testing at the Indiana University FIT Core, 2) questions asked by the research team, and 3) information gathered from the participants medical records.
Research will be conducted at the Medical Genetics clinic in the Pediatric Care Center. Blood will be draw at IU Health and at the FIT Core.
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Ehlers-danlos syndrome, EDS, Hypophosphatasia, HPP
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Age: 18 years - 65 years
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Gender: All
Inclusion Criteria
• Adults 18-65.
• Patients who have a diagnosis of EDS or HSD. hEDS and HSD will be established based on the 2017 diagnostic criteria, which are clinically based, since no genetic testing is available at this time for hEDS or HSD.
Exclusion Criteria
• Those not meeting diagnostic criteria for EDS or HSD.
