Endocrine Abstracts

Introduction: Generalised arterial calcification of infancy (GACI) is a rare autosomal-recessive disorder, associated with high mortality rate, due to inactivating mutations in ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene that results in arterial stenosis secondary to unregulated hydroxyapatite deposition.

Case report: A female baby was born at 34+5 weeks to consanguineous parents with a birth weight of 3.97 kg. Baby was born in poor condition at birth and subsequently developed Persistent Pulmonary Hypertension. She required high frequency ventilation and nitric oxide. On day three of life, echocardiogram showed severe pulmonary regurgitation with echogenic aorta and main pulmonary artery. CT chest and abdomen on day five of life showed heavy calcification throughout almost all of pulmonary arteries and aorta and subclavian, internal mammary, cephalic, and axillary arteries. She developed renal failure due to left renal artery stenosis and hepatic failure with left liver lobe infarction due to calcification in portal and hepatic veins. Serum calcium, phosphate, PTH and alkaline phosphatase levels were normal. Sequencing of ENPP1 identified a novel homozygous frameshift mutation in exon 25 (c.2662_2662del, p.R888FsX), predicted to result in production of a truncated protein. Despite treatment with IV pamidromate at 0.1 mg/kg per week, there was a progressive decline in neurological function from day twenty of life and intensive care was subsequently withdrawn.

Conclusion: We report a novel nonsense mutation causing a severe phenotype of GACI affecting the heart, lungs, kidney, liver and brain. Although treatment with bisphosponates improves outcomes in small proportion of cases, in our case there was no discernable response to therapy and the infant died due to multi organ failure secondary to GACI.

No formalised treatment approach exists for individuals affected by GACI although bisphosphonates are reported to reduce arterial calcification and improve in mortality rate. The optimum duration of bisphosphonate therapy for patients with GACI remains unclear.