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NCT Number: NCT07745179

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

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.

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Key information

Conditions

Ectonucleotide Pyrophosphatase/Phosphodiesterase1 Deficiency ATP-Binding Cassette Subfamily C Member 6 Deficiency Arterial calcification of infancy Autosomal Recessive Hypophosphatemic Rickets Cardiovascular Diseases Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Connective Tissue Diseases Generalized Arterial Calcification of Infancy Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Hypophosphatemic Rickets, Autosomal Recessive, 1 PXE (Pseudoxanthoma Elasticum) Pseudoxanthoma Elasticum Skin Abnormalities Skin Diseases Skin Diseases, Genetic Skin and Connective Tissue Diseases Vascular Diseases

Age range

1 day and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Centre de References des Maladies Neuromusculaires (CRMN), La Tronche, France

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About this study

Study INZ701-006 is a multicenter, retrospective, observational natural history study designed to evaluate disease presentation and progression in infant, pediatric, and adult subjects with ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) Deficiency and in subjects with the early-onset form of adenosine triphosphate-binding cassette transporter subfamily C member 6 (ABCC6) Deficiency.

The study will utilize data obtained from medical records, radiographic imaging, and other available sources to characterize the physiological, anatomical, and functional manifestations of ENPP1 Deficiency and early-onset ABCC6 Deficiency.

For eligible subjects, historical data will be retrospectively abstracted from medical records and other available sources from birth, or earlier when available, through the date of informed consent, loss to follow-up, death, or another defined data cutoff, as applicable.

No study intervention will be administered as part of this observational study.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Participants were eligible for inclusion if they met at least one of the following criteria:

  • 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.

Exclusion criteria

  • 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.

Treatment and study plan

Primary outcomes

  1. Participants with Ectopic Calcification

    Time frame: 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).

    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.

  2. Participants With Disease-Related Skeletal Abnormalities

    Time frame: 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).

    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.

Secondary outcomes

  1. Global Rickets Severity Score

    Time frame: 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).

    Assessment of rickets severity using the Global Rickets Severity Score (RSS), which was derived from radiographic evaluations. Score (0 to 10), with higher scores indicating greater severity of rickets.

  2. Height Z-Score

    Time frame: 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).

    Assessment of longitudinal growth using height measurements obtained from medical records. Height measurements were converted to age- and sex-adjusted height Z-scores using WHO and CDC growth standards. The measured variable was height Z-score, reported as standard deviations (SD) from the reference population mean.

  3. Weight Z-Score

    Time frame: 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).

    Assessment of longitudinal growth using weight measurements obtained from medical records. Weight measurements were converted to age- and sex-adjusted weight Z-scores using WHO and CDC growth standards. The measured variable was weight Z-score, reported as standard deviations (SD) from the reference population mean.

  4. Serum Phosphate Concentration

    Time frame: 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).

    Assessment of serum phosphate concentration obtained from clinical laboratory evaluations documented in medical records. The measured variable was serum phosphate concentration, reported in milligrams per deciliter (mg/dL) or converted to a common unit for analysis where appropriate.

  5. Fibroblast Growth Factor 23 (FGF23) Concentration

    Time frame: 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).

    Assessment of fibroblast growth factor 23 (FGF23) concentration obtained from clinical laboratory evaluations documented in medical records. The measured variable was FGF23 concentration, reported in picograms per milliliter (pg/mL) according to local laboratory methodology.

  6. Parathyroid Hormone (PTH) Concentration

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

    Assessment of parathyroid hormone (PTH) concentration obtained from clinical laboratory evaluations documented in medical records. The measured variable was serum PTH concentration, reported in picograms per milliliter (pg/mL) according to local laboratory methodology.

  7. Inorganic Pyrophosphate (PPi) Concentration

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

    Assessment of inorganic pyrophosphate (PPi) concentration obtained from clinical laboratory evaluations documented in medical records. The measured variable was PPi concentration, reported in micromoles per liter (µmol/L) according to local laboratory methodology.

Sponsors and collaborators

Lead sponsor

Inozyme Pharma

Industry

Registry information

Official study title

A Retrospective, Longitudinal Natural History Study of Subjects With ENPP1 Deficiency or the Early-Onset Form of ABCC6 Deficiency

Important dates

Study start
2018
Primary completion
2023
Study completion
2025
First posted
Aug 4, 2026
Registry last updated
Aug 4, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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