Calcification of the Left Atrial Appendage in Autosomal Recessive Hypophosphatemic Rickets Type 2 (ENPP1 mutation)

Background Autosomal recessive hypophosphatemic rickets type 2 (ARHR2) is a rare genetic condition associated with renal phosphate wasting secondary to elevated FGF-23. Generalized arterial calcification of infancy (GACI) is associated with ARHR2, but late-onset vascular calcifications are less reported. The objective of this report is to describe an adult patient with no prior diagnosis of GACI presenting extensive calcifications of the left atrial appendage, mitral valve, and ascending aortic wall. Case Report A 32-year-old woman was referred for chronic hypophosphatemia and diffuse musculoskeletal pain associated with early osteoarthritis and enthesopathy. Physical examination revealed a 30-mmHg pressure difference between her arms suggesting subclavian artery stenosis. Imaging then revealed extensive calcifications in the left atrial appendage, mitral valve, ascending aortic wall and a coronary calcium score (Agatston) of zero. Her past treatment consisted of phosphate and activated vitamin D supplementation between the ages of 7 and 18. The patient also underwent several orthopedic surgeries and a subtotal parathyroidectomy at age 13 for hypercalcemic hyperparathyroidism. She had a history of hypertension and developed preeclampsia at 33 weeks' gestation during a previous pregnancy. Discussion The clinical continuum between GACI and ARHR2 remains unclear, and this case suggests that early subclinical vascular calcifications may remain undetected until adulthood. Conclusion This case highlights the importance of vascular screening following an ARHR2 diagnosis to assess for potential calcifications. More data on the natural progression of the disease is needed to better understand the effects of conventional therapy and hyperparathyroidism on the risk of calcifications in this condition.