Skip to content

IEMbase 0780: ENPP1-related ectonucleotide pyrophosphatase-phosphodiesterase 1 deficiency

Scope

Field Value
IEMbase ID 780
Nosology 16.3.12.01
Nosology code IEM0037
Gene ENPP1
External IDs OMIM:208000; ORPHA:51608
Generated mapping AMBIGUOUS; Arterial_Calcification_of_Infancy and subtype ENPP1-related
Candidate DisMech targets Arterial_Calcification_of_Infancy.yaml subtype ENPP1-related
Review date 2026-07-08

IEMbase phenotype signal

IEMbase labels this autosomal recessive record as ENPP1-related ectonucleotide pyrophosphatase-phosphodiesterase 1 deficiency, with alternate name generalized arterial calcification of infancy type 1 and abbreviation GACI1. The source signal includes neonatal/infantile arterial calcification, renal artery calcification, calcification of cardiac valve rings and aorta, hypertension, cardiac failure, coronary artery disease, myocardial infarction, early death, prenatal signs such as fetal distress, polyhydramnios, or pericardial effusion, joint calcifications, hearing loss, angioid streaks, and dental findings including ankylosis, hypercementosis, and infraocclusion.

DisMech phenotype coverage

Arterial_Calcification_of_Infancy.yaml is the correct local target. It has an explicit ENPP1-related subtype, models ENPP1 loss as defective extracellular ATP hydrolysis and reduced pyrophosphate generation, and captures arterial calcification, arterial stenosis, hypertension, congestive heart failure, FGF23-mediated renal phosphate wasting, hypophosphatemic rickets, and hearing loss in ENPP1-deficient survivors.

Concordance and completeness

Judgement: exact subtype coverage; generated ambiguity reflects disease-level and subtype-level matches.

The gene, OMIM identity, inheritance, GACI1 identity, pyrophosphate mechanism, arterial calcification/stenosis, hypertension, heart failure, survivor rickets, and hearing loss are concordant. IEMbase provides useful granularity beyond the current local phenotype set: prenatal presentation, renal artery and coronary territory disease, valve/aortic-ring calcification, myocardial infarction, joint calcification, angioid streaks, and dental ankylosis/hypercementosis/ infraocclusion are not all modeled as discrete DisMech phenotypes.

Curation actions

  • Treat Arterial_Calcification_of_Infancy.yaml subtype ENPP1-related as exact local coverage for IEMbase 0780.
  • Preserve the ENPP1-specific rickets, phosphate/FGF23, and hearing-loss survivor phenotype already present locally.
  • Consider future phenotype additions for prenatal signs, dental disease, angioid streaks, renal/coronary/valve calcification, myocardial infarction, and joint/enthesis calcification.