Endocrine Abstracts

JOINT1962

Background: ENPP1 Deficiency is a rare autosomal recessive disorder with an estimated prevalence of 1 in 64, 000 pregnancies. It results in low inorganic pyrophosphate levels, leading to excessive soft tissue calcification, neointimal proliferation, and impaired bone mineralisation. Approximately 50% of affected infants succumb to generalised arterial calcification of infancy (GACI) within the first six months. Survivors may develop hypophosphatemic rickets, hearing loss, osteomalacia, vascular calcification, and cardiac complications. Pregnancy in women with ENPP1 Deficiency remains undocumented.

Case Presentation: We present a 32-year-old woman with ENPP1 Deficiency, currently in her second pregnancy. Her past medical history includes hypophosphatemic rickets managed with Alfacalcidol and phosphate replacement, congenital cervical spine fusion (C2-C3), and minor vascular calcification. Her twin brother died at six weeks from severe GACI. She has received lifelong metabolic bone and cardiology care. Her first pregnancy was managed in a Maternal Medicine Centre (MMC) with multi-disciplinary management. Her initial bone chemistry was within normal ranges and remained stable throughout pregnancy. The bone profile was monitored closely as the placenta can produce PTHrP in variable amounts, requiring potential dose adjustments of Alfacalcidol. She remained on Alfacalcidol 1 mg and Phosphate Sandoz 4 tablets daily. Due to increased risk of hypertension, pre-eclampsia, and fetal growth restriction, she was commenced on prophylactic aspirin (150 mg/day). Obstetric cardiology assessments showed normal ECG and echocardiogram findings. Low molecular weight heparin prophylaxis was initiated after MDT discussion. At 23 weeks, she had a positive placental screen with bilateral notches and a mean placenta pulsatility index of 1. 46 and she commenced home blood pressure monitoring and fetal growth surevillance. Normal fetal growth velocity was maintained and delivered at 36+4 weeks via elective cesarean section due to hypertension and abnormal placental growth factor (PIGF). In her second pregnancy, also managed at MMC, initial assessment revealed hypophosphatemia with mild secondary hyperparathyroidism (PTH 7. 8 pmol/l, PO₄^2- 0. 73 mmol/l, Adjusted Ca²⁺ 2. 34 mmol/l). She remains on the same dose of Alfacalcidol and Phosphate Sandoz. She is 23 weeks gestation with reassuring cardiology assessments. Placental screen shows no notches and borderline raised pulsatility index indicating a lower risk of placental pathology.

Conclusion: Pregnancy in women with ENPP1 Deficiency requires multidisciplinary care at a Maternal Medicine Centre. Pre-conception counselling should address potential complications, emphasising cardiovascular risk assessment. Close monitoring for metabolic bone disease, cardiac complications, and hypertensive disorders, along with individualised management plans, is crucial to optimising maternal and fetal outcomes.