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Current Osteoporosis Reports
Published in: Current Osteoporosis Reports 3/2020

01-06-2020 | Bisphosphonate | Rare Bone Disease (C Langman and E Shore, Section Editors)

Generalized Arterial Calcification of Infancy: New Insights, Controversies, and Approach to Management

Authors: Alison M. Boyce, Rachel I. Gafni, Carlos R. Ferreira

Published in: Current Osteoporosis Reports | Issue 3/2020

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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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Metadata
Title
Generalized Arterial Calcification of Infancy: New Insights, Controversies, and Approach to Management
Authors
Alison M. Boyce
Rachel I. Gafni
Carlos R. Ferreira
Publication date
01-06-2020
Publisher
Springer US
Published in
Current Osteoporosis Reports / Issue 3/2020
Print ISSN: 1544-1873
Electronic ISSN: 1544-2241
DOI
https://doi.org/10.1007/s11914-020-00577-4

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