Generalized Arterial Calcification of Infancy: Fatal Clinical Course Associated with a Novel Mutation in ENPP1.

Generalized arterial calcification of infancy (GACI) is a rare condition characterized by arterial calcification within the internal elastic lamina associated with intimal proliferation, leading to stenosis of great and medium-sized vessels. This disease, caused by mutations in multiple exons of ENPP1, frequently results in death in infancy. Nowadays, the most promising therapeutic compounds for this rare disease are bisphosphonates. We describe a case of GACI associated with the novel mutation c.653A>T (p.D218V) in ENPP1 on both alleles. The male infant was delivered prematurely and developed heart failure, severe hypertension, and diffuse calcifications of all arterial districts. He was treated with etidronate (18 mg/kg/day); however, the clinical condition did not improve, and a resolution of calcifications was not observed. The infant died within the 6th month of life of ischemic heart failure. We conclude that even if the diagnosis of GACI is established early and bisphosphonate treatment is started early, the prognosis can be very poor.