Autosomal Recessive Hypophosphatemic Rickets type 2 (ARHR2) is a rare genetic condition secondary to a loss-of-function mutation in ENPP1 gene. ARHR2 is associated with renal phosphate wasting and suppressed 1,25-dihydroxyvitamin D due to increased FGF-23 levels and causing abnormal bone mineralization. Furthermore, as ENPP1 is implicated in the generation of PPi (inorganic pyrophosphate) which inhibits hydroxyapatite deposition, some ARHR2 patients present with life-treating generalized arterial calcification of infancy (GACI). We reported the case of a 32-year-old woman with a known diagnosis of ARHR2 since the age of seven. At that time, she presented a growth failure, bowed legs but no GACI history. She was treated from the age of 7 to 18 with phosphate supplements and calcitriol. She had ten surgeries for her leg deformities and had a subtotal parathyroidectomy at age 13 for primary hyperparathyroidism. She was referred to a tertiary centre for management of hypophosphatemia and diffuse bone pain. The alkaline phosphatase was at the upper limit of normal but imagings, including computed tomography scans and bone scintigraphy, did not show pseudofractures. Her chronic pain was associated with osteoarthritis and periarticular calcifications. She was treated for hypertension, and had a history of preeclampsia at 33 weeks of pregnancy. At the physical exam, a 30 mm Hg systolic blood pressure differential was noted between the right and left arms, suspect of severe subclavian artery stenosis. Additional investigations demonstrated a normal cardiac ultrasound (US), an Agatson score of 0 (coronary calcium scan) but extensive calcifications of the left atrial appendage, dense calcifications of the mitral valve and numerous calcifications in the ascending aortic wall. The spectrum of clinical manifestations associated with ENPP1-related conditions (GACI and ARHR2) is still unclear. In some patients who survive GACI, resolution of vascular calcifications has been reported. Furthermore, this case raises the possibility of undetected vascular calcifications in the infancy uncovered only after the diagnosis of ARHR2. Previous cases reported pulmonary stenosis, thickening of the aortic valve, and increased carotid intima-media thickness in patients with ARHR2 phenotype. Left atrial calcifications have been described in mechanical valve replacement, mitral stenosis, post-radiotherapy and in chronic kidney disease. Recommendations of cardiac US and kidney US have been proposed at the diagnosis of AHRH2. We further suggest vascular screening with cardiac scans to examine large vessels, and calcium score in these patients.
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