Six cases of ENPP1 pathogenic variants causing autosomal recessive hypophosphatemic rickets type 2 and generalized arterial calcification of infancy

Autosomal recessive hypophosphatemic rickets type 2 (ARHR2) and generalized arterial calcification of infancy (GACI) occur secondary to biallelic ectonucleotide pyrophosphate/phosphodiesterase 1 (ENPP1) loss-of-function pathogenic variants. GACI is a life-threatening condition, often presenting in the neonatal period with heart failure and hypertension, caused by calcification of the media in large- and medium-sized arteries.

Citation:
Collins L, Sandy J, Ly S, Lomax KE, ……. Siafarikas A. Six cases of ENPP1 pathogenic variants causing autosomal recessive hypophosphatemic rickets type 2 and generalized arterial calcification of infancy. JBMR Plus. 2025;9:v47-v57.

Keywords:
autosomal recessive hypophosphatemic rickets type 2 (ARHR2); ectonucleotide pyrophosphate/phosphodiesterase 1 (ENPP1); fibroblast growth factor 23 (FGF23); generalized arterial calcification of infancy (GACI); hypophosphatemic rickets

Abstract:
Autosomal recessive hypophosphatemic rickets type 2 (ARHR2) and generalized arterial calcification of infancy (GACI) occur secondary to biallelic ectonucleotide pyrophosphate/phosphodiesterase 1 (ENPP1) loss-of-function pathogenic variants. GACI is a life-threatening condition, often presenting in the neonatal period with heart failure and hypertension, caused by calcification of the media in large- and medium-sized arteries.