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

  • Rare Bone Disease (C Langman and E Shore, Section Editors)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

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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Funding

This research was supported by the Intramural Research Programs of the NIDCR and NHGRI, National Institutes of Health.

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Authors and Affiliations

  1. Skeletal Diseases and Mineral Homeostasis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive Room 218 MSC 4320, Bethesda, MD, 20892, USA

    Alison M. Boyce & Rachel I. Gafni

  2. Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA

    Carlos R. Ferreira

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  1. Alison M. Boyce
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  2. Rachel I. Gafni
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  3. Carlos R. Ferreira
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Correspondence to Alison M. Boyce.

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Conflict of Interest

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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