Hypophosphatasia
Conditions
Keywords
Hypophosphatasia, Hypophosphatasemia, Musculoskeletal complaints, Rare disease, Genetic disorder, Alkaline phosphatase gene, ALP, ALP gene, Rheumatic disease, COHIR study, Prevalence, Diagnostic Algorithm, Metabolic bone diseases
Brief summary
With hypophosphatasia still being frequently overlooked and misdiagnosed, the primary aim of this prospective observational study is to determine the prevalence of hypophosphatasia in adult patients in rheumatology, and beyond that to establish an algorithm that promotes early hypophosphatasia detection in clinical practice.
Detailed description
Hypophosphatasia (HPP) is a rare genetic disorder (1-3/300,000 severe cases in Europe) caused by one or more mutations in the alkaline phosphatase (ALP) gene. Hypomineralization results in symptoms such as arthralgias, insufficiency fractures, and poor dental status beginning in childhood. A fatal outcome is conceivable in circumstances of early infancy first presentation. In consistency with the musculoskeletal complaint pattern, HPP is far more common in the rheumatology patient population than in the general population. However, HPP is still frequently misdiagnosed as some other form of bone disease (e.g., rickets, osteomalacia, or osteoporosis). Therefore, implementation of a clinically applicable algorithm for early hypophosphatasia detection is needed. The primary aim of this prospective observational study is to determine the prevalence of hypophosphatasia in adult patients in rheumatology. Moreover, a further goal is to establish an algorithm that reliably separates adult HPP patients from other, rheumatologic and bone diseases.
Interventions
DIAGNOSTIC_TESTSecond alkaline phosphatase measurement
(2-4 weeks after the 1st measurement)
DIAGNOSTIC_TESTExtended laboratory diagnostics
Laboratory testing investigating features that support the diagnosis of hypophosphatasia or exclude it by indicating secondary hypophosphatasemia for other reasons (including parameters such as serum calcium, inorganic serum phosphate, vitamin B6, vitamin B12, folic acid, bone-specific alkaline phosphatase, vitamin D3, and more).
DIAGNOSTIC_TESTSymptom and clinical findings checklist for hypophosphatasia
Checklist including numerous symptoms and clinical findings regarding the musculoskeletal system and non-musculoskeletal body parts
DIAGNOSTIC_TESTSF-36
Quality of life questionnaire
DIAGNOSTIC_TESTShort physical performance battery (SPPB) score
The short physical performance battery is a group of measures that combines the results of the gait speed, chair stand and balance tests. It has been used as a predictive tool for possible disability and can aid in the monitoring of function in older or disease-affected people. The scores range from 0 (worst performance) to 12 (best performance). The SPPB has been shown to have predictive validity showing a gradient of risk for mortality, nursing home admission, and disability.
DIAGNOSTIC_TESTPhysical examination
A full rheumatological examination will be performed.
DIAGNOSTIC_TESTRecording of vital signs
(including body temperature, blood pressure, heart rate)
DIAGNOSTIC_TESTBioelectrical Impedance Analysis
A body composition measurement by BIA (Bioelectrical Impedance Analysis \[proportional mass of muscle, water and fat in kg\]) will be performed.
DIAGNOSTIC_TESTGenetic testing of the alkaline phosphatase gene
Investigation of mutations regarding the alkaline phosphatase gene
Sponsors
University of Bonn
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written Informed consent * Age \> 18 years * Clinical suspicion of hypophosphatasia * Evidence of a pathological ALP value within the clinical routine screening
Exclusion criteria
* Failure to meet the inclusion criteria listed above
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prevalence of hypophosphatasia in adult patients in rheumatology | 24 months | The primary aim of this prospective observational study is to determine the prevalence of hypophosphatasia in adult patients presenting with musculoskeletal symptoms in rheumatology. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Health-related quality of life: Short Form-36 | 24 months | The possible score ranges from 0 to 100 points, where 0 points represent the greatest possible health limitation, while 100 points represent no health limitation at all. |
| Frequency of specific symptoms and clinical findings in patients with hypophosphatasia | 24 months | This will be derived from the symptom and clinical findings checklist. |
| Frequency of musculoskeletal pathology in hypophosphatasia patients in comparison with normal controls. | 24 months | Frequency of musculoskeletal pathology in people with biochemistry suggestive of hypophosphatasia and positive ALP gene test as compared with normal controls. |
| Correlation between physical performance abnormalities and hypophosphatasia | 24 months | Physical performance is determined by standardized short physical performance battery |
| Correlation between body composition abnormalities and hypophosphatasia | 24 months | Body composition is determined by bioelectrical impedance analysis. |
| Frequency of specific patient history findings and the occurence of hypophosphatasia | 24 months | Data will be derived from the medical history of hypophosphatasia patients (patient clinical data will be collected regarding the diagnosis, onset, progression, treatment course and outcome for patients with hypophosphatasia) |
Countries
Germany
Contacts
Primary ContactValentin S. Schäfer, Dr. med.
Outcome results
None listed