ENPP1 deficiency is typically associated with arterial calcification early in life; there is a bimodal distribution, with about half of all patients presenting in the perinatal period (in utero or within a week of life), while the other half presents at about 2-3 months of life. The arterial calcification can be detected as echobrightness in utero as early as 18 weeks gestation, while complications such as pericardial effusions are frequent. Cardiac failure is the most common complication caused by the calcifications, and the most common cause of death. Other complications include stroke, and bowel ischemia. Some patients only develop diffuse fibrointimal hyperplasia leading to arterial narrowing, even in the absence of calcifications. Periarticular calcification is seen in about one third of patients.
Patients who survive the first 6 months of life are likely to develop hypophosphatemic rickets after infancy. Some patients develop rickets even in the absence of known prior arterial calcification. Hearing loss is also a common finding. Less common findings include PXE-like retinal changes (such as angioid streaks), and PXE-like skin changes.
Inheritance is autosomal recessive. The calculated prevalence of the disease is estimated at 1 in 200,000 individuals, using carrier rates from ExAC.