Autosomal recessive hypophosphatemic rickets type 2 (ARHR2) due to ENPP1-deficiency

• Published in: Bone (New York, N.Y.) N.Y.), 2021-12, Vol.153, p.116111-116111, Article 116111
• Main Authors: Höppner, Jakob, Kornak, Uwe, Sinningen, Kathrin, Rutsch, Frank, Oheim, Ralf, Grasemann, Corinna
• Format: Article
• Language: English
• Subjects: Autosomal recessive hypophosphatemic rickets type 2 (ARHR2); ENPP1; Familial Hypophosphatemic Rickets - genetics; FGF23; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Generalized arterial calcification of infancy (GACI); Humans; Phosphates; Phosphoric Diester Hydrolases - genetics; Pyrophosphatases - genetics; Rickets, Hypophosphatemic - genetics
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2021.116111

Awareness for hypophosphatemic rickets has increased in the last years, based on the availability of specific medical treatments. Autosomal recessive hypophosphatemic rickets type 2 (ARHR2) is a rare form of hypophosphatemic rickets, which is known to develop in survivors of generalized arterial calcification of infancy (GACI). Both disorders are based on a deficiency of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) and present with a high clinical variability and a lack of a phenotype-genotype association. ARHR2 is characterized by phosphate wasting due to elevated fibroblast growth factor 23 (FGF23) levels and might represent a response of the organism to minimize ectopic calcification in individuals with ENPP1-deficiency. This report reviews the recent clinical and preclinical data on this ultra-rare disease in childhood. •Deficiency of ENPP1 is associated GACI and ARHR2.•GACI and ARHR2 are recognized as two distinct clinical phenotypes which manifest at different ages.•ARHR2 is associated with elevated levels of FGF23, however FGF23-targeted treatments might increase the risk for ectopic calcification.