Characteristics of Hypophosphatasia in Adult Patients in Rheumatology (COHIR)

University of Bonn

Status: Enrolling

Conditions: Hypophosphatasia

Treatments: Diagnostic Test: Genetic testing of the alkaline phosphatase gene; Diagnostic Test: Bioelectrical Impedance Analysis; Diagnostic Test: Short physical performance battery (SPPB) score; Diagnostic Test: Second alkaline phosphatase measurement; Diagnostic Test: Physical examination; Diagnostic Test: SF-36; Diagnostic Test: Symptom and clinical findings checklist for hypophosphatasia; Diagnostic Test: Extended laboratory diagnostics; Diagnostic Test: Recording of vital signs

Study type: Observational

Funder types: Other

Identifiers

NCT06161142

407/21

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

60 participants in 2 patient groups

Persistant hypophosphatasemia

Description:

Patients with persistant hypophosphatasemia are highly suspicious for hypophosphatasia, and as such are the main focus of this study. In case of persistently low alkaline phosphatase (2nd measurement, 2-4 weeks after the 1st measurement) with normal serum calcium and phosphate values (exclusion of secondary hypophosphatemia due to e.g. rickets or malnutrition) and exclusion of other causes of secondary hypophosphatemia, genetic testing for a pathological ALP gene is performed as part of routine diagnostics. This study involves the structured recording of specific symptoms, the entire course of the disease since childhood, laboratory parameters and genetic testing.

Treatment:

Diagnostic Test: Bioelectrical Impedance Analysis

Diagnostic Test: Symptom and clinical findings checklist for hypophosphatasia

Diagnostic Test: Physical examination

Diagnostic Test: Extended laboratory diagnostics

Diagnostic Test: SF-36

Diagnostic Test: Short physical performance battery (SPPB) score

Diagnostic Test: Second alkaline phosphatase measurement

Diagnostic Test: Genetic testing of the alkaline phosphatase gene

Diagnostic Test: Recording of vital signs

Transient hypophosphatasemia (Control group without hypophosphatasia)

Description:

In patients, in which the initial hypophosphatasemia does not confirm with the second ALP testing, the former suspicion of hypophosphatasia must be discarded. With the exclusion of a hypophosphatasia (characterized by a persistant hypophosphatasemia among other criteria) this group of patients qualifies as a control group of patients without hypophosphatasia. Data from this control group will be analyzed in order to investigate patient historical, clinical and laboratory features that may help in the discrimination of hypophosphatasia patients against healthy individuals.

Treatment:

Diagnostic Test: Bioelectrical Impedance Analysis

Diagnostic Test: Symptom and clinical findings checklist for hypophosphatasia

Diagnostic Test: Physical examination

Diagnostic Test: SF-36

Diagnostic Test: Short physical performance battery (SPPB) score

Diagnostic Test: Second alkaline phosphatase measurement

Diagnostic Test: Recording of vital signs