Natural History Study: ENPP1 Deficiency or the Early-Onset Form of ABCC6 Deficiency

NCT07745179 | Completed

• 1 other identifier: INZ701-006
• Study Type: observational
• Target: 23
• Locations: 4 countries
• Sites: 8

Brief Summary

The purpose of this study is to characterize the natural history of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) Deficiency and the early-onset form of adenosine triphosphate binding cassette transporter subfamily C member 6 (ABCC6) Deficiency through retrospective review of medical records and other available data sources. Information collected on medical history, clinical manifestations, radiographic imaging, and other disease-related assessments may be used to support the development of future therapies for these diseases.

Conditions

Ectonucleotide Pyrophosphatase/phosphodiesterase1 Deficiency; ATP-Binding Cassette Subfamily C Member 6 Deficiency; Generalized Arterial Calcification of Infancy; Autosomal Recessive Hypophosphatemic Rickets; PXE (Pseudoxanthoma Elasticum)

Keywords

Ectonucleotide pyrophosphatase/phosphodiesterase 1 deficiency; ENPP1; ATP-binding cassette subfamily C member 6 deficiency; ABCC6; Generalized Arterial Calcification of Infancy; GACI; Autosomal Recessive Hypophosphatemic Rickets Type 2; ARHR2; Hypopyrophosphatemia; PXE (Pseudoxanthoma Elasticum); ectopic calcification; Arterial calcification; Intraarticular calcification; Aortic calcification

Outcome Measures

Primary Outcomes (2)

• Participants with Ectopic Calcification

  Assessment of the occurrence of ectopic calcification documented in available imaging records. Ectopic calcification was identified based on radiologist or investigator interpretation of imaging assessments. The measure was the number of participants with documented ectopic calcification.

  Retrospective assessment of available historical records collected from birth through informed consent, loss to follow-up, or death, whichever occurred first (up to approximately 33 years).

• Participants With Disease-Related Skeletal Abnormalities

  Assessment of the occurrence of disease-related skeletal abnormalities documented in available medical records and imaging reports. Skeletal abnormalities were identified based on clinical diagnoses and radiographic findings recorded by treating physicians. The measure was the number of participants with documented skeletal abnormalities.

  Retrospective assessment of available historical records collected from birth through informed consent, loss to follow-up, or death, whichever occurred first (up to approximately 33 years).

Secondary Outcomes (7)

• Global Rickets Severity Score

  Retrospective assessment of available radiographic evaluations collected from birth through informed consent, loss to follow-up, or death, whichever occurred first (up to approximately 33 years).

• Height Z-Score

  Retrospective assessment of available height measurements collected from birth through informed consent, loss to follow-up, or death, whichever occurred first (up to approximately 33 years).

• Weight Z-Score

  Retrospective assessment of available weight measurements collected from birth through informed consent, loss to follow-up, or death, whichever occurred first (up to approximately 33 years).

• Serum Phosphate Concentration

  Retrospective assessment of available serum phosphate measurements collected from birth through informed consent, loss to follow-up, or death, whichever occurred first (up to approximately 33 years).

• Fibroblast Growth Factor 23 (FGF23) Concentration

  Retrospective assessment of available FGF23 measurements collected from birth through informed consent, loss to follow-up, or death, whichever occurred first (up to approximately 33 years).

Eligibility Criteria

• Age: 1 Day+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Infant, pediatric, and adult participants with ENPP1 Deficiency or early-onset ABCC6 Deficiency, including participants with generalized arterial calcification of infancy (GACI), whose diagnoses were confirmed by genetic testing and/or clinical phenotype and who had medical records available for retrospective review.

You may qualify if:

• Generalized arterial calcification of infancy (GACI) genotype, defined as two pathogenic mutations in ENPP1 and/or ABCC6, confirmed by mutational analysis, and a GACI phenotype confirmed by imaging or biopsy.
• GACI phenotype confirmed by imaging or biopsy, with mutational analysis demonstrating that each parent carried at least one mutation in ENPP1 and/or ABCC6.
• Biallelic mutations in ENPP1 and a clinical phenotype consistent with ENPP1 Deficiency.
• Mutational analysis demonstrating that each parent carried at least one mutation in ENPP1, together with clinical signs and symptoms consistent with ENPP1 Deficiency in the participant.
• Availability of medical records and source documentation sufficient for retrospective review.

You may not qualify if:

• Insufficient medical records, imaging studies, or source documentation to support retrospective data collection.
• Diagnosis not consistent with ENPP1 Deficiency, GACI, or early-onset ABCC6 Deficiency.
• Inability to obtain informed consent from the participant or legally authorized representative, as required by local regulations.

Sponsors & Collaborators

• Inozyme Pharma: lead

Study Sites (8)

Children's Hospital of Philadelpha

Philadelphia, Pennsylvania, 19104, United States

Location

Centre de References des Maladies Neuromusculaires (CRMN)

La Tronche, France

Location

Hospices Civils de Lyon

Lyon, France

Location

Hopital Necker-Enfants Malades

Paris, France

Location

University Hospital Munster

Münster, Germany

Location

Birmingham Children's Hospital

Birmingham, United Kingdom

Location

Evelina London Children's Hospital

London, 19104, United Kingdom

Location

Royal Manchester University Hospital

Manchester, United Kingdom

Location

MeSH Terms

Conditions

Arterial calcification of infancy; Hypophosphatemic Rickets, Autosomal Recessive, 1; Pseudoxanthoma Elasticum

Condition Hierarchy (Ancestors)

Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: RETROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2021
• First Posted: August 4, 2026
• Study Start: December 5, 2018
• Primary Completion: June 8, 2023
• Study Completion: February 14, 2025
• Last Updated: August 4, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3); FR (3); US (1); DE (1)