Endocrine Abstracts

Generalised arterial calcification of infancy (GACI) is a rare genetic disorder caused by inactivating variants in the ENPoc10.6 with estimated incidence of 1:200,000 pregnancies. Mortality estimated at 55% within first 6 months. It is characterised by arterial intimal calcification leading to stenosis affecting all major vessels. The index case presented with hypo-phosphataemic rickets at 18 months of age. Genetic testing demonstrated a novel mutation in Ectonucleotide pyrophosphatase-phosphodiesterase (ENPP1) gene which required further functional mRNA analysis. ENPP1 is also associated with GACI. Further imaging did not demonstrate any cardiovascular calcification. Sadly, at 4.4 years of age he passed away following a brief illness. A post-mortem noted some heart muscle fibrosis which may have been due to early life arterial calcification. The subsequent pregnancy demonstrated extensive arterial calcification and the mother was treated with oral Etidronate (a first-generation non-nitrogen containing bisphosphonate) during the last 2 weeks of the pregnancy. The infant was born at 35 weeks gestation weighing 2.95 kg. There was extensive severe calcification of the major arteries including calcification of the aorta, pulmonary and carotid arteries. Furthermore there was also calcification in the shoulders and peri-articular tissues. She had reno-vascular hypertension requiring angioplasty and also had cardiovascular compromise. Medical treatment included Aspirin and Amlodipine. More specific treatment to stabilise the calcification was commenced with Etidronate to aid calcium absorption is sodium thiosulphate 3g IV once daily 5 days a week was used. both continued for about a year and This resulted in gradual resolution of the calcification and marked clinical improvement. She developed biochemistry consistent with hypophosphataemic rickets and commenced on oral alfacalcidol and phosphate. She is now 5 years old. These two siblings demonstrate the diverse phenotypes in ENPP1 mutations. If present; GACI is associated with a poor prognosis, but this does improve after the first year of life. There may still be residual arterial abnormalities even after resolution of the calcification as assumed in her brother. Medical treatment with Etidronate and Sodium Thiosulphate probably contributed to the improvement. Both children had hypophosphataemic rickets. The sister is being evaluated for an international study for enzyme replacement therapy.