Abstract for presentation at 11th International Congress of Human Genetics

Infantile Arterial Calcification: Successful Treatment with Bisphosphonates

  • Ms Bronwyn Culling, Department of Molecular and Clinical Genetics, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
  • Dr Alison Loughran-Fowlds, Departments of Neonatology, Endocrinology and Academic Medical Genetics, The Children's Hospital at Westmead, Wesdmead, NSW, Australia
  • Dr Craig Munns, Departments of Neonatology, Endocrinology and Academic Medical Genetics, The Children's Hospital at Westmead, Wesdmead, NSW, Australia
  • Prof David Sillence, Departments of Neonatology, Endocrinology and Academic Medical Genetics, The Children's Hospital at Westmead, Wesdmead, NSW, Australia
  • Ms Corrina Walsh, SEALS Molecular and Cytogenetics Laboratory, NSW, Australia
  • Mr Peter Taylor, SEALS Molecular and Cytogenetics Laboratory, NSW, Australia
  • Dr Michael Buckley, SEALS Molecular and Cytogenetics Laboratory, NSW. Centre for Vascular Research, NSW, Australia
  • Dr Frank Rutsch, Department of General Pediatrics, University Children's Hospital, Muenster, Germany
  • Dr Tony Roscioli, Molecular and Clinical Genetics Unit, Royal Prince Alfred Hospital, Sydney, NSW, Australia

    • Infantile arterial calcification (IAC) is a rare, usually fatal disorder, caused by inactivation of the ENPP1 gene. It is characterized by generalised calcification of the arterial internal elastic lamina, leading to rupture of the lamina and occlusive changes in the intima. Most infants die within the first 6 months of life of vaso-occlusive disease, especially of the coronary arteries. We report 2 siblings with IAC, one of whom is being successfully treated with bisphosphonates. Molecular genetic testing confirmed compound heterozygosity for ENPP1 mutations in both siblings. The first sibling died at 8 days of age of cardiac failure. Antenatal screening by ultrasonography of the second sibling did not detect arterial calcification. Arterial calcification was confirmed after birth with Doppler ultrasound and echocardiography. No peripheral pulses were palpable at birth. Treatment with low dose cyclical Pamidronate 0.1mg/Kg weekly was commenced on day 7 and continued for 4 weeks, followed by weekly oral Risedronate 5mg. Improvement in arterial calcification has been noted which is continuing at 5 months of age with improvement in renal blood flow, disappearance of coronary artery calcification and palpable femoral pulses after only 6 weeks of treatment. Low dose bisphosphonates strongly bind to calcium phosphate and inhibit crystal formation and aggregation. Early treatment with low dose bisphosphonates may reduce the morbidity and high incidence of mortality in these infants.

    Conference Organiser - ICMS Pty Ltd