Generalized arterial calcification of infancy: Fatal clinical course associated with a novel mutation in ENPP1

Abstract

Generalized arterial calcification of infancy(GACI) is a rare condition characterized by arterial calcificationwithin the internal elastic lamina associated with intimalproliferation, leading to stenosis of great and medium-sizedvessels. This disease, caused by mutations in multiple exonsof ENPP1, frequently results in death in infancy. Nowadays,the most promising therapeutic compounds for this rare diseaseare bisphosphonates. We describe a case of GACI associatedwith the novel mutation c.653A>T (p.D218V) inENPP1 on both alleles. The male infant was delivered prematurelyand developed heart failure, severe hypertension,and diffuse calcifications of all arterial districts. Hewas treated with etidronate (18 mg/kg/day); however, theclinical condition did not improve, and a resolution of calcificationswas not observed. The infant died within the 6thmonth of life of ischemic heart failure. We concludethat even if the diagnosis of GACI is established early andbisphosphonate treatment is started early, the prognosis canbe very poor.