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Generalized Arterial Calcification of Infancy: Fatal Clinical Course Associated with a Novel Mutation in ENPP1

  • Silvia Galletti
  • Yvonne Nitschke
  • Anna M. Malavolti
  • Giulia Aquilano
  • Giacomo Faldella
  • Luigi Corvaglia
  • Frank RutschEmail author
Chapter
Part of the JIMD Reports book series (JIMD, volume 1)

Abstract

Generalized arterial calcification of infancy (GACI) is a rare condition characterized by arterial calcification within the internal elastic lamina associated with intimal proliferation, leading to stenosis of great and medium-sized vessels. This disease, caused by mutations in multiple exons of ENPP1, frequently results in death in infancy. Nowadays, the most promising therapeutic compounds for this rare disease are bisphosphonates. We describe a case of GACI associated with the novel mutation c.653A>T (p.D218V) in ENPP1 on both alleles. The male infant was delivered prematurely and developed heart failure, severe hypertension, and diffuse calcifications of all arterial districts. He was treated with etidronate (18 mg/kg/day); however, the clinical condition did not improve, and a resolution of calcifications was not observed. The infant died within the 6th month of life of ischemic heart failure. We conclude that even if the diagnosis of GACI is established early and bisphosphonate treatment is started early, the prognosis can be very poor.

Keywords

Bisphosphonates Heart failure Myocardial infarction Inorganic pyrophosphate 

Notes

Acknowledgment

Y.N. and F.R are supported by a grant from the Interdisciplinary Center for Clinical Research, Münster University.

References

  1. Atkin I, Ornoy A, Pita JC et al (1988) EHDP-induced rachitic syndrome in rats is not reversed by vitamin D metabolites. Anat Rec 220(1):22–30PubMedCrossRefGoogle Scholar
  2. Ciana G, Colonna F, Forleo V et al (1997) Idiopathic arterial calcification in infancy: effectiveness of prostaglandin infusion for treatment of secondary hypertension refractory to conventional therapy: a case report. Pediatr Cardiol 18:67–71PubMedCrossRefGoogle Scholar
  3. Ciana G, Trappan A, Bembi B et al (2006) Generalized arterial calcification in infancy: two siblings with prolonged survival. Eur J Pediatr 165:258–263PubMedCrossRefGoogle Scholar
  4. Dlamini N, Splitt M, Durkan A et al (2009) Generalized arterial calcification of infancy: phenotypic spectrum among three siblings including one case without obvious arterial calcifications. Am J Med Genet A 149A:456–460Google Scholar
  5. Eronem M, Pohjavuori M, Heikkila P (2001) Fatal outcome of two siblings with idiopathic arterial calcification of infancy diagnosed in utero. Pediatr Cardiol 22:167–169CrossRefGoogle Scholar
  6. Glatz AC, Pawel BR, Hsu DT et al (2006) Idiopathic Infantile arterial calcification: two case reports, a review of the literature and a role for cardiac transplantation. Pediatr Transplant 10:225–233PubMedCrossRefGoogle Scholar
  7. Gleason MM, Weber HS, Curan SE et al (1994) Idiopathic infantile arterial calcinosis: intermediate-term survival and cardiac sequelae. Am Heart J 127:691–695PubMedCrossRefGoogle Scholar
  8. Johnson K, Polewski M, van Etten D et al (2005) Chondrogenesis mediated by PPi depletion promotes spontaneous aortic calcification in NPP1-/- mice. Arterioscler Thromb Vasc Biol 25(4):686–691PubMedCrossRefGoogle Scholar
  9. Levine JC, Campbell J, Nadel A (2001) Prenatal diagnosis of idiopathic infantile arterial calcification. Circulation 103:325–326PubMedCrossRefGoogle Scholar
  10. Levy-Litan V, Hershkovitz E, Avizov L et al (2010) Autosomal-recessive hypophosphatemic rickets is associated with an inactivation mutation in the ENPP1 gene. Am J Hum Genet 86:273–278Google Scholar
  11. Lorenz-Depiereux B, Schnabel D et al (2010) Loss-of-function ENPP1 mutations cause both generalized arterial calcification of infancy and autosomal-recessive hypophosphatemic rickets. Am J Hum Genet 86:267–272Google Scholar
  12. Moran JJ (1975) Idiopathic arterial calcification of infancy: a clinicopathologic study. Pathol Annu 10:393–417PubMedGoogle Scholar
  13. Pao DG, DeAngelis GA, Lovell MA (1998) Idiopathic arterial calcification in infancy: sonographic and magnetic resonance findings with pathologic correlation. Pediatr Radiol 28:256–259PubMedCrossRefGoogle Scholar
  14. Patel M, Savvas A, Rustum S et al (2004) Idiopathic arterial calcification in childhood. Pediatr Radiol 34:652–655PubMedCrossRefGoogle Scholar
  15. Ramjan KA, Roscioli T, Rutsch F et al (2009) Generalized arterial calcification of infancy: treatment with bisphosphonates. Nat Clin Pract Endocrinol Metab 5:167–172PubMedCrossRefGoogle Scholar
  16. Rutsch F, Vaingankar S, Johnson K et al (2001) PC-1 nucleoside triphosphate pyrophosphohydrolase deficiency in idiopathic infantile arterial calcification. Am J Pathol 158:543–554PubMedCrossRefGoogle Scholar
  17. Rutsch F, Ruf N, Vaingankar S et al (2003) Mutations in ENPP1 are associated with “idiopathic” infantile arterial calcification. Nat Genet 34(4):379–381PubMedCrossRefGoogle Scholar
  18. Rutsch F, Böyer P, Nitschke Y et al (2008) Hypophosphatemia, hyperphosphaturia, and bisphosphonate treatment are associated with survival beyond infancy in generalized arterial calcification of infancy. Circ Cardiovasc Genet 1:133–140PubMedCrossRefGoogle Scholar
  19. Sholler GF, Yu JS et al (1984) Generalized arterial calcification in infancy: three case reports, including spontaneous regression with long-term survival. J Pediatr 105:257–260PubMedCrossRefGoogle Scholar
  20. Terkeltaub RA (2001) Inorganic pyrophosphate generation and disposition in pathophysiology. Am J Physiol Cell Physiol 281:C1–C11PubMedGoogle Scholar
  21. Tran KH, Boechat MI (2006) Idiopathic infantile arterial calcification: imaging evaluation and the usefulness of MR angiography. Pediatr Radiol 36:247–253PubMedCrossRefGoogle Scholar
  22. Van Der Sluis IM, Boot AM, Vernooij M et al (2006) Idiopathic infantile arterial calcification: clinical presentation, therapy and long-term follow-up. Eur J Pediatr 165:590–593PubMedCrossRefGoogle Scholar

Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  • Silvia Galletti
    • 1
  • Yvonne Nitschke
    • 2
  • Anna M. Malavolti
    • 1
  • Giulia Aquilano
    • 1
  • Giacomo Faldella
    • 1
  • Luigi Corvaglia
    • 1
  • Frank Rutsch
    • 3
    Email author
  1. 1.Department of Gynecological, Obstetric and Pediatric SciencesUniversity Hospital of BolognaBolognaItaly
  2. 2.Department of General PediatricsMuenster University Children’s HospitalMuensterGermany
  3. 3.Klinik und Poliklinik für Kinder-und JugendmedizinUniversitätsklinikum MünsterMünsterGermany

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