Abstract
Purpose of Review
This review summarizes current understanding of generalized arterial calcification of infancy (GACI), emphasizing pathophysiology, clinical presentation, and approaches and controversies in management.
Recent Findings
Identification of causative ENPP1 mutations revealed that GACI arises from deficiencies in inorganic pyrophosphate (leading to calcifications) and adenosine monophosphate (leading to intimal proliferation). Identification of genotypic and phenotypic overlap with pseudoxanthoma elasticum and autosomal recessive hypophosphatemic rickets further advanced understanding of GACI as a complex, multisystemic disease. Clinical data is limited to small, retrospective samples; it is therefore unknown whether commonly used medications, such as bisphosphonates and hypophosphatemia treatment, are therapeutic or potentially harmful. ENPP1-Fc replacement represents a promising approach warranting further study.
Summary
Knowledge gaps in natural history place clinicians at high risk of assigning causality to interventions that are correlated with changes in clinical status. There is thus a critical need for improved natural history studies to develop and test targeted therapies.
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This research was supported by the Intramural Research Programs of the NIDCR and NHGRI, National Institutes of Health.
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The NIH receives funding from Inozyme for research related to GACI. The NIDCR receives research funding from Amgen and QED, outside the submitted work. Dr. Gafni serves as an advisory board member to Ascendis and an unpaid member of the medical advisory board for GACI Global.
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Boyce, A.M., Gafni, R.I. & Ferreira, C.R. Generalized Arterial Calcification of Infancy: New Insights, Controversies, and Approach to Management. Curr Osteoporos Rep 18, 232–241 (2020). https://doi.org/10.1007/s11914-020-00577-4
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DOI: https://doi.org/10.1007/s11914-020-00577-4