Abstract
Generalized arterial calcification of infancy (GACI, OMIM 208000) and pseudoxanthoma elasticum (PXE, OMIM 264800) are rare autosomal-recessive disorders which represent the opposite ends of the same spectrum of pathologies characterized by progressive ectopic calcification and degeneration of elastic fibers at skin, eyes, and cardiovascular level. Patients with GACI suffer from hypertension, severe myocardial ischemia, and congestive heart failure and often die within 6 months of life. On the other end, PXE is associated with considerable morbidity, rarely with mortality. GACI and PXE are associated with biallelic mutations in ENPP1 and in ABCC6. We report the case of a 4-year-old Italian child submitted to heart transplant, at 18 months old, for end-stage heart failure due to extensive myocardial infarction of the left ventricle and diffuse coronary calcifications. The histology showed generalized arterial calcification and the molecular analysis identified mutations in ABCC6. Two years after transplantation, the child shows good clinical conditions and growth with no recurrence of calcium deposits in the heart.
Conclusion: Bisphosphonate therapy at present is the treatment of choice for systemic arterial involvement in GACI, and heart transplant has proven to be the definitive treatment in case with extensive myocardial infarction, as in our. Molecular analysis is mandatory for a complete diagnosis and familial counseling.
Similar content being viewed by others
Abbreviations
- CT:
-
Computed tomography
- GACI:
-
Generalized arterial calcification of infancy
- PCR:
-
Polymerase chain reaction
- PXE:
-
Pseudoxanthoma elasticum
References
Edouard T, Chabot G, Miro J, Buhas DC, Nitschke Y, Lapierre C, Rutsch F, Alos N (2011) Efficacy and safety of 2-year etidronate treatment in a child with generalized arterial calcification of infancy. Eur J Pediatr 170(12):1585–1590
Glatz AC, Pawel BR, Hsu DT, Weinberg P, Chrisant MR (2006) Idiopathic infantile arterial calcification: two case reports, a review of the literature and a role for cardiac transplantation. Pediatr Transplant 10(2):225–233, Review
Le Boulanger G, Labrèze C, Croué A, Schurgers LJ, Chassaing N, Wittkampf T, Rutsch F, Martin L (2010) An unusual severe vascular case of pseudoxanthoma elasticum presenting as generalized arterial calcification of infancy. Am J Med Genet A 152A(1):118–123
Le Saux O, Beck K, Sachsinger C, Silvestri C, Treiber C, Göring HH, Johnson EW, De Paepe A, Pope FM, Pasquali-Ronchetti I, Bercovitch L, Marais AS, Viljoen DL, Terry SF, Boyd CD (2001) A spectrum of ABCC6 mutations is responsible for pseudoxanthoma elasticum. Am J Hum Genet 69:749–764
Li Q, Schumacher W, Jablonski D, Siegel D, Uitto J (2012) Cutaneous features of pseudoxanthoma elasticum in a patient with generalized arterial calcification of infancy due to a homozygous missense mutation in the ENPP1 gene. Br J Dermatol 166(5):1107–1111
Marrott PK, Newcombe KD, Becroft DM, Friedlander DH (1984) Idiopathic infantile arterial calcification with survival to adult life. Pediatr Cardiol 5((2):119–122
Meradji M, de Villeneuve VH, Huber J, de Bruijn WC, Pearse RG (1978) Idiopathic infantile arterial calcification in siblings: radiologic diagnosis and successful treatment. J Pediatr 92(3):401–405
Nitschke Y, Baujat G, Botschen U, Wittkampf T, du Moulin M, Stella J, Le Merrer M, Guest G, Lambot K, Tazarourte-Pinturier MF, Chassaing N, Roche O, Feenstra I, Loechner K, Deshpande C, Garber SJ, Chikarmane R, Steinmann B, Shahinyan T, Martorell L, Davies J, Smith WE, Kahler SG, McCulloch M, Wraige E, Loidi L, Höhne W, Martin L, Hadj-Rabia S, Terkeltaub R, Rutsch F (2012) Generalized arterial calcification of infancy and pseudoxanthoma elasticum can be caused by mutations in either ENPP1 or ABCC6. Am J Hum Genet 90(1):25–39
Nitschke Y, Rutsch F (2012) Generalized arterial calcification of infancy and pseudoxanthoma elasticum: two sides of the same coin. Front Genet 3:302
Rutsch F, Böyer P, Nitschke Y, Ruf N, Lorenz-Depierieux B, Wittkampf T, Weissen-Plenz G, Fischer RJ, Mughal Z, Gregory JW, Davies JH, Loirat C, Strom TM, Schnabel D, Nürnberg P, Terkeltaub R, GACI Study Group (2008) Hypophosphatemia, hyperphosphaturia, and bisphosphonate treatment are associated with survival beyond infancy in generalized arterial calcification of infancy. Circ Cardiovasc Genet 1(2):133–140
Sholler GF, Yu JS, Bale PM, Hawker RE, Celermajer JM, Kozlowski K (1984) Generalized arterial calcification of infancy: three case reports, including spontaneous regression with long-term survival. J Pediatr 105(2):257–260
Uitto J, Bercovitch L, Terry SF, Terry PF (2011) Pseudoxanthoma elasticum: progress in diagnostics and research towards treatment: Summary of the 2010 PXE International Research Meeting. Am J Med Genet A 55A(7):1517–1526
Acknowledgments
We gratefully thank Dr. Rosaria Cristantielli (Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA) for the English’s revision and Mr. Gabriele Bacile for graphical assistance.
Author information
Authors and Affiliations
Corresponding author
Additional information
Communicated by Beat Steinmann
Authors summary
At the present time, bisphosphonate therapy is the treatment of choice for generalized arterial calcification of infancy (GACI). In case of extensive myocardial infarction, like the one presented here, heart transplant represents the definitive treatment. Molecular analysis is mandatory for a complete diagnosis and familial counseling.
Rights and permissions
About this article
Cite this article
Giovannoni, I., Callea, F., Travaglini, L. et al. Heart transplant and 2-year follow up in a child with generalized arterial calcification of infancy. Eur J Pediatr 173, 1735–1740 (2014). https://doi.org/10.1007/s00431-014-2447-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00431-014-2447-7