ESPE2022 Poster Category 1 Bone, Growth Plate and Mineral Metabolism (46 abstracts)
Background:Calcium-sensing receptors (CaSR) located on parathyroid glands and kidneys act to regulate serum calcium levels. Inherited hypocalciuric hypercalcaemia and autosomal dominant hypercalciuric hypocalcaemia are due to inactivating and activating CaSR mutations respectively. We present the immediate and medium term postoperative clinical course of the first paediatric patient with hypercalciuric hypocalcaemia managed with a simultaneous parathyroid and kidney transplantation after failure of medical therapy.
Case presentation: A 1 year-old Caucasian girl, with no family history, presented with hypocalcaemic convulsions with a corrected calcium of 1.42 mmol/l [2.19-2.69 pmol/L], undetectable PTH <0.5 pmol/l [0.95 – 5.7 pmol/L], normal vitamin D levels and high urinary calcium creatinine (Ca:Cr) ratio (5 mmol/mmol). Renal ultrasound detected bilateral nephrocalcinosis. Molecular analysis identified an activating mutation of CaSR (c.2528C>A p.A843E). Initial management consisted of 1-alphahydroxycholecalciferol and calcium but increasing urinary Ca:Cr ratios worsened nephrocalcinosis. Hypocalcaemic seizures were poorly controlled so daily subcutaneous injections of recombinant PTH was introduced at 1.5y and subsequent subcutaneous PTH infusion was started at the age of 2.5 years via an insulin pump. PTH infusion improved hypercalciuria but hypocalcaemia management remained challenging with hypocalcaemic seizures and progressive metabolic bone disease. She presented with slipped bilateral upper femoral epiphyses at 10.6y. Renal function remained normal until age of 9, before deteriorating to end stage kidney disease at the age of 11.3y (eGFR 10ml/min/1.73m2) needing haemodialysis and listed for transplant. The etiology of this remains uncertain as renal ultrasound showed bilateral cortical cysts but with no signs of nephrocalcinosis or nephrolithiasis. At 11.8y she simultaneously received a kidney and a parathyroid gland from her father who did not carry any pathogenic variations in the CaSR. Postoperatively, PTH infusion and calcium supplementation was recommenced and weaned with the aim to maintain corrected serum calcium just below the normal range. This was to stimulate the endogenous PTH graft production (Peak level 28 ng/l [10-65 ng/L]). At 22 weeks post transplantation the PTH pump could be completely stopped although she remained on calcium and vitamin D supplementation. 2 years post transplantation there was evidence of parathyroid transplant failure with hypocalcaemia and inappropriately low serum PTH (19 ng/L). Alfacalcidol was reintroduced, however the urinary Ca:Cr ratio remained low (0.7).
Conclusion: The case highlights the benefits and clinical course of a paediatric patient with an activating mutation in the CaSR managed with a simultaneous parathyroid and kidney transplantation.
15 Sep 2022 - 17 Sep 2022