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

Inozyme Pharma23 enrolled

Overview

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.

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Ectonucleotide Pyrophosphatase/phosphodiesterase1 Deficiency ATP-Binding Cassette Subfamily C Member 6 Deficiency

Eligibility

Sex: ALLMin age: 1 Day

Medical Language ↔ Plain English

Inclusion Criteria Participants were eligible for inclusion if they met at least one of the following criteria: 1. 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. 2. GACI phenotype confirmed by imaging or biopsy, with mutational analysis demonstrating that each parent carried at least one mutation in ENPP1 and/or ABCC6. 3. Biallelic mutations in ENPP1 and a clinical phenotype consistent with ENPP1 Deficiency. 4. 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. 5. Availability of medical records and source documentation sufficient for retrospective review. Exclusion Criteria 1. Insufficient medical records, imaging studies, or source documentation to support retrospective data collection. 2. Diagnosis not consistent with ENPP1 Deficiency, GACI, or early-onset ABCC6 Deficiency. 3. Inability to obtain informed consent from the participant or legally authorized representative, as required by local regulations.

Locations (8)

Children's Hospital of Philadelpha

Philadelphia, Pennsylvania, United States

Centre de References des Maladies Neuromusculaires (CRMN)

La Tronche, France

Hospices Civils de Lyon

Lyon, France

Hopital Necker-Enfants Malades

Paris, France

University Hospital Munster

Münster, Germany

Birmingham Children's Hospital

Birmingham, United Kingdom

Evelina London Children's Hospital

London, United Kingdom

Royal Manchester University Hospital

Manchester, United Kingdom

Outcomes

Primary Outcomes

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.

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).

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.

Secondary Outcomes

Global Rickets Severity Score

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.

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).

Height Z-Score

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.

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).

Weight Z-Score

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.

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).

Serum Phosphate Concentration

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.

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).

Fibroblast Growth Factor 23 (FGF23) Concentration

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.

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).

Parathyroid Hormone (PTH) Concentration

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.

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).

Inorganic Pyrophosphate (PPi) Concentration

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.

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).