hypophosphatasia
Conditions
Interventions
None listed
Sponsors
Osaka University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Patients who have not been treated with asfotase alfa 2.Patients aged younger than 6 months at the time of enrollment 3.Patients diagnosed as hypophosphatasia 4.Patients who fall under any of the following items (1) to (6), and who are judged by the physicians to be likely to have HPP (1)The serum total ALP level is lower than the standard value for the age and gender. (2)Fetal ultrasound findings 1)Markedly short extremities (femur length (FL) of -4SD or less in the second and third pregnancy trimesters) 2)Fraying of metaphysis 3)Craniotabes (deformation of the cranial bone by mild compression by a probe) 4)Thoracic hypoplasia (3)Fetal CT findings 1)Marked ossification insufficiency in the whole body 2)Shortening of long bones 3)Metaphyseal cupping 4)Thoracic hypoplasia (4)Following radiographic findings unique to HPP 1)Metaphyseal flaring and fraying 2)Systemic osteopenia 3)Enlargement of growth cartilage area 4)Findings of the metaphyseal radiolucent tongue-like protrusion or sclerosis (5)Two or more items in the following HPP-related findings are satisfied. 1)Past or present history of the following conditions 1.Prenatal or postnatal non-traumatic fracture 2.Delay in fracture healing 2)Past history of nephrocalcinosis and hypercalcemia 3)Craniosynostosis 4)Respiratory dysfunction or rickets-like thoracic deformation 5)Vitamin B6-dependent convulsive seizures 6)Failure to thrive (6)Mutation in the ALPL gene encoding tissue-nonspecific alkaline phosphatase has been identified. 5.Patients for whom informed consent can be obtained in writing from their legally authorized representatives
Exclusion criteria
Exclusion criteria: 1.Patients diagnosed as having rickets from causes other than HPP, such as vitamin D deficient rickets 2.Patients diagnosed as skeletal dysplasia other than HPP, such as osteogenesis imperfecta and campomelic dysplasia 3.Patients with serum calcium concentrations or phosphorus concentrations lower than the lower limit of the institutional standard values of the study sites 4.The serum total ALP level is not lower than the lower limit of the standard values for corresponding age and gender. 5.Patients participating in clinical trials using the drugs, medical devices or treatment methods that are not approved in Japan or at study sites 6.Patients having clinically significant diseases, who is judged by investigators not to be able to participate in this study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| >Evaluation of bone based on radiographs using Rickets Severity Scale (RSS) and modified Radiographic global impression of change(mRGI-C) as a validated scale of HPP(0, 12, 24, 48, 72, 96week) >Time until intervention with artificial respiratory therapy becomes necessary in the patients who have not received artificial respiratory therapy at the beginning of the observation period (0, 12, 24, 48, 72, 96week) >In the patients who have necessitated artificial respiratory therapy at the beginning of the observation period or during the observation period, evaluation will be made based on the status of artificial respirator, respiratory support time (including the duration of the use of artificial respirator or the duration of oxygen inhalation), frequency of ventilation with artificial respirator or oxygen flow rate, pressure of artificial respirator, and fraction of inspiratory oxygen (FiO2). (0, 12, 24, 48, 72, 96week) >Body weight, height, arm span, head circumference and chest circumference will be determined and physical development will be examined and evaluated. (0, 12, 24, 48, 72, 96week) >Intellectual and motor development will be evaluated using Kyoto Scale of Psychological Development (K scale). (48, 96week) >The clinical course of HPP in teeth will be examined and evaluated on the basis of the clinical findings such as the number, time and site of teeth lost, depth of the periodontal pockets, periodontal bleeding, tooth mobility and dental formula, and imaging evaluation of morphological abnormalities of teeth and dental age on radiographs. (48, 72, 96week) >Gross motor function test will be conducted using Denver IIgross motor development scale. (24, 48, 72, 96week) >Hearing test will be conducted using the auditory brain stem response (ABR) to evaluate the status of impaired hearing. (0, 24week) | — |
Secondary
| Measure | Time frame |
|---|---|
| Health Outcomes >ADL will be evaluated using PedsQL and CHAQ. (96week) Biomarkers >PLP, PL (0 or cord blood sample, 12, 24, 48, 72, 96week) and metabolites detected by metabolome technology in plasma 0 or cord blood, 12, 48week will be determined to evaluate the usefulness as metabolic markers >P1NP, CTX, Sclerostin, FGF23 and factors related with bone metabolism tested by multi-plex analysisin serum will be determined as bone metabolism markers to investigate the usefulness as markers reflecting bone quality (0 or cord blood, 12, 48week) >Bone mineral content and bone mineral density will be determined as the markers for ossification using dual-energy X-ray absorptiometry, and the bone mass in the process of ossification in HPP patients will be quantified. Moreover, Lean Body Mass will be determined by DXA as a quantitative marker for muscle mass (48, 96week) | — |
Countries
Japan
Contacts
Public ContactTakuo Kubota
Osaka University Dept. of Pediatrics, Graduate School of Medicine
Outcome results
None listed