Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 DeficiencyATP-Binding Cassette Subfamily C Member 6 Deficiency
Investigational drug(s) / intervention(s)
No Intervention for this observational study
No Intervention for this observational study: No Intervention for this observational study
Study summary
The purpose of this prospective registry is to characterize the natural history of ectonucleotide pyrophosphatase/phosphodiesterase1(ENPP1) Deficiency and the infantile-onset form of adenosine triphosphate (ATP) binding cassette transporter protein subfamily C member 6 (ABCC6) Deficiency longitudinally. The registry will prospectively gather information about the genetic, biochemical, physiological, anatomic, radiographic, and functional manifestations (including patient reported outcomes \[PROs\]) of each disease during routine, standard-of-care visits, with the aim of developing a comprehensive understanding of the burden of illness and progressive nature of the disease.
Eligibility
Sex
ALL
Min age
—
Max age
—
Healthy volunteers
No
Inclusion Criteria:
Individuals eligible to participate must meet all the following inclusion criteria:
1. Must provide written or electronic consent after the nature of the registry has been explained, and prior to any research-related procedures, per International Council for Harmonisation (ICH) Good Clinical Practice (GCP)
2. Agree to provide access to relevant medical records
3. One of the following genetic or clinical criteria
1. A confirmed prenatal or postnatal molecular genetic diagnosis of ENPP1 Deficiency with biallelic mutations (ie, homozygous or compound heterozygous) performed by a College of American Pathologists/Clinical Laboratory Improvement Amendments (CAP/CLIA) certified laboratory or regional equivalent
OR
2. Monoallelic ENPP1 mutation confirmed by a certified CAP/CLIA laboratory or regional equivalent and any of the following clinical symptoms:
i. ≥ 1 traumatic vertebral fracture
ii. ≥ 2 fractures as an adult (eg, long-bones, digits, vertebrae)
iii. Low bone mineral density (dual-energy X-ray absorptiometry \[DXA\] Z-score \<1.5) and \<55 years of age
iv. Bone or joint pain interfering with movement or daily activities
v. History of myocardial infarction (MI), unstable angina, transient ischemic attack (TIA) or low cardiac output before the age of 40 yrs.
vi. History of rickets or bone deformity
vii. Diagnosis of ossification of the posterior longitudinal ligament (OPLL)
viii. Other clinical symptoms, with approval by Inozyme
OR
c. A confirmed prenatal or postnatal molecular genetic diagnosis of ABCC6 Deficiency with biallelic mutations confirmed by a certified CAP/CLIA laboratory or regional equivalent, and \<18 years of age
Exclusion Criteria:
Individuals who meet the following exclusion criteria will not be eligible to participate:
1. Participant or their legally designated representative does not have the cognitive capacity to provide informed consent
2. Patients who are currently participating in an INZ-701 interventional clinical study, with the exception of expanded access programs and long-term safety follow-up studies
1. Participants in interventional studies may be approached for inclusion in the registry once their involvement in the treatment period of the clinical study has been completed
Primary outcome measure(s)
Characterization of the natural history of ENPP1 Deficiency and the infantile-onset form of ABCC6 Deficiency longitudinally — Annually up to 10 years Assessments will be collected during each subject's routine visit. The assessments will be done per local standard of care.
Assessment of Patient Functional changes through a validated Patient Reported Outcomes (PROs) tool — Annually up to 10 years For each subject, patient function will be assessed using the appropriate Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaires. These may include: PROMIS Cognitive Function, PROMIS Fatigue, PROMIS Pain Intensity, PROMIS Pain Interference and PROMIS Physical Function. Each questionnaire is scored on a 5-point Likert scale ranging from 1 (never) to 5 (always). High scores indicate more of the domain being measured (eg, more fatigue, more physical function). Raw scores are converted to T-Scores based on a mean of 50 and a standard deviation of 10, allowing comparison of the sample to the general population.
Parent Proxy questionnaires will be used for children aged 5 to \<18 years
Assessment of Health-Related Quality-of-Life (HRQoL) changes through validated Patient Reported Outcomes (PROs) tools — Annually up to 10 years For each subject, HRQoL will be assessed using the following scales:
age 5 to \<18 years: Pediatric QoL scales (Short Form \[SF\]-10, Caregiver Global Impression of Status/Severity \[CaGI-S\]);
age ≥18 years: Adult QoL scales (Short Form \[SF\]-36, Patient Global Impression of Status/Severity \[PGI-S\])
The SF-10 is a 10-item caregiver-completed questionnaire for assessment of physical and psychosocial HRQoL in children. Each question has 5 options ranging from "Excellent" to "Poor". Higher scores are associated with better HRQoL.
The SF-36 measures a broad spectrum of physical and mental health domains, including physical functioning, role limitations due to physical and emotional problems, bodily pain, general health perceptions, vitality, social functioning, and emotional well-being. The SF-36 generates scores ranging from 0-100 with higher scores associated with better HRQoL.
The CaGI-S and PGI-S will be scored across a 7-point scale with lower scores associated with better HRQoL.
Measurement of inorganic phosphate (PPi) levels in patients' venous blood — Annually up to 10 years For each subject, QoL will be assessed using the following scales: global clinical impression of severity (GCI-S) and, short form 10 health survey for children and short form 36 health survey for adults short form 10 health survey for children and short form 36 health survey for adults
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
We use cookies to analyse site traffic and improve your experience. With your consent, we may also use cookies for advertising. You can change your choice at any time on our Cookie Policy page. See also our Privacy Policy.