Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Case Study
  • Published:

Generalized arterial calcification of infancy: treatment with bisphosphonates

Nature Reviews Endocrinology volume 5, pages 167–172 (2009)Cite this article

A Correction to this article was published on 01 April 2009

Abstract

Background A baby girl developed respiratory distress immediately after birth and required supplemental oxygen. She was born at term via lower-segment cesarean section. The parents were nonconsanguineous, and antenatal ultrasonography during the pregnancy at 18 and 32 weeks of gestation did not reveal any abnormalities. On examination at birth, no pulses were palpable; however, the baby's blood pressure was normal and no remarkable abnormalities were detected. Ultrasonography revealed widespread arterial calcification.

Investigations Chest and abdominal radiography at birth and serial abdominal, renal and cardiac ultrasonography at follow-up examinations; dual-energy X-ray absorptiometry during treatment with bisphosphonates; genetic screening.

Diagnosis Generalized arterial calcification of infancy, secondary to compound, heterozygous mutations in the ENPP1 gene, pL661V and pE668K of the paternal chromosome, and pN792S in the maternal chromosome.

Management Low-dose disodium pamidronate (0.1 mg/kg per week for 4 weeks), which commenced on the seventh day after birth and was changed to oral risedronate sodium (1 mg/kg per week as a single dose) at 4 weeks of age. Complete resolution of arterial calcification was seen by 3 months of age. At 12 months, ergocalciferol was added at a dose of 5,000 U daily for 6 weeks, followed by 200 U daily owing to the patient's vitamin D deficiency and elevated parathyroid hormone level. Treatment with bisphosphonates is ongoing, but is planned to be discontinued at 3 years of age. The child has remained healthy and developmentally normal.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Genetic pedigree of the patient's family.
Figure 2: Ultrasound and X-ray scans of the patient described.
Figure 3: Physiological effects of ENPP1 mutations.

References

  1. Rutsch F et al. (2003) Mutations in ENPP1 are associated with “idiopathic” infantile arterial calcification. Nat Genet 34: 379–381

    Article  CAS  PubMed  Google Scholar 

  2. Glatz AC et al. (2006) Idiopathic infantile arterial calcification: two case reports, a review of the literature and a role for cardiac transplantation. Pediatr Transplant 10: 225–233

    Article  PubMed  Google Scholar 

  3. Numakura C et al. (2006) Genetic and enzymatic analysis for two Japanese patients with idiopathic infantile arterial calcification. J Bone Miner Metab 24: 48–52

    Article  PubMed  Google Scholar 

  4. van der Sluis IM et al. (2006) Idiopathic infantile arterial calcification: clinical presentation, therapy and long-term follow-up. Eur J Pediatr 165: 590–593

    Article  PubMed  Google Scholar 

  5. Ciana G et al (2006) Generalized arterial calcification of infancy: two siblings with prolonged survival. Eur J Pediatr 165: 258–263

    Article  PubMed  Google Scholar 

  6. Cheng KS et al (2005) Generalized arterial calcification of infancy: different clinical courses in two affected siblings. Am J Med Genet A 136: 210–213

    Article  PubMed  Google Scholar 

  7. Tran KH and Boechat MI (2006) Idiopathic infantile arterial calcification: imaging evaluation and the usefulness of MR angiography. Pediatr Radiol 36: 247–253

    Article  PubMed  Google Scholar 

  8. Russell RG et al. (2007) Bisphosphonates: mode of action and pharmacology. Pediatrics 119 (Suppl 2): S150–S162

    Article  PubMed  Google Scholar 

  9. Meradji M et al. (1978) Idiopathic infantile arterial calcification in siblings: radiologic diagnosis and successful treatment. J Pediatr 92: 401–405

    Article  CAS  PubMed  Google Scholar 

  10. Marrott PK et al. (1984) Idiopathic infantile arterial calcification with survival to adult life. Pediatr Cardiol 5: 119–122

    Article  CAS  PubMed  Google Scholar 

  11. Van Dyck M et al. (1989) Idiopathic infantile arterial calcification with cardiac, renal and central nervous system involvement. Eur J Pediatr 148: 374–377

    Article  CAS  PubMed  Google Scholar 

  12. Ylitalo R et al. (1998) Accumulation of bisphosphonates in human artery and their effects on human and rat arterial function in vitro . Pharmacol Toxicol 83: 125–131

    Article  CAS  PubMed  Google Scholar 

  13. Johnson K et al. (2005) Chondrogenesis mediated by PP1 depletion promotes spontaneous aortic calcification in NPP1−/− mice. Arterioscler Thromb Vasc Biol 25: 686–691

    Article  CAS  PubMed  Google Scholar 

  14. Buckley MF et al. (1990) Plasma cell membrane glycoprotein PC-1. cDNA cloning of the human molecule, amino acid sequence, and chromosomal location. J Biol Chem 265: 17506–17511

    CAS  PubMed  Google Scholar 

  15. Rauch F and Glorieux FH (2004) Osteogenesis imperfecta. Lancet 363: 1377–1385

    Article  CAS  PubMed  Google Scholar 

  16. Munns CF et al. (2007) Acute phase response and mineral status following low dose intravenous zoledronic acid in children. Bone 41: 366–370

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge C Walsh for undertaking ENPP1 molecular genetic analysis, M McQuade for coordinating the bisphosphonate treatment, and PH Gallego for reviewing the manuscript. Written consent for publication was obtained from a responsible relative of the patient. Désirée Lie, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

Author information

Authors and Affiliations

  1. KA Ramjan is a Pediatric Endocrine Fellow, and CFJ Munns is a Senior Staff Specialist of Bone and Mineral Medicine, both at the Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Australia ,

    Kim A Ramjan & Craig FJ Munns

  2. T Roscioli is a Clinical Geneticist at Sydney South-West Area Health Service, and D Sillence is Professor of Genetic Medicine at the University of Sydney, Australia ,

    Tony Roscioli & David Sillence

  3. F Rutsch is Assistant Professor of Pediatrics at the University Children's Hospital Münster, Germany.,

    Frank Rutsch

Authors
  1. Kim A Ramjan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tony Roscioli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Frank Rutsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. David Sillence
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Craig FJ Munns
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kim A Ramjan.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ramjan, K., Roscioli, T., Rutsch, F. et al. Generalized arterial calcification of infancy: treatment with bisphosphonates. Nat Rev Endocrinol 5, 167–172 (2009). https://doi.org/10.1038/ncpendmet1067

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncpendmet1067

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing