ESPE Abstracts (2021) 94 P2-64

1Department of Neonatology, The Children’s Hospital & The Institute of Child Health, Lahore, Pakistan; 2Department of Paediatric Endocrinology and Diabetes, The Children’s Hospital & The Institute of Child Health, Lahore, Pakistan; 3Department of Paediatric Endocrinology and Diabetes, Hameed Latif Hospital, Lahore, Pakistan; 4Department of Paediatric Gastroenterology and hepatology, The Children’s Hospital & The Institute of Child Health, Lahore, Pakistan; 5Department of Paediatric Surgery, Hameed Latif Hospital, Lahore, Pakistan

Background: Neonatal severe hyperparathyroidism (NSHPT) is a rare disorder caused by inactivating calcium-sensing receptor (CASR) mutation characterized by striking hyperparathyroidism leading to severe hypercalcemia. Heterozygous loss of function in CASR gives rise to a benign variant called familial hypocalciuric hypercalcemia which needs no treatment. We are reporting 3 cases of NSHPT due to inactivating homozygous CASR mutation not responding to cinacalcet.

Results: We identified 3 cases (2 females) from three families of neonatal severe hyperparathyroidism (NSHPT) due to inactivating CASR mutation. Two were carrying homozygous mutation in CASR gene (parents’ carrier) while in one patient’s genetic analysis could not be done (later both parents found carrier). Case 1 had a novel CASR variant at c.295G>C p.(Asp99His), case 2 had CASR variant at c.2069G>A p.(Arg690His) and case 3 had CASR variant at c.206G>A p.(Arg69His). All cases were born to consanguineous parents with history of unexplained sibling death in case 1 and still birth in case 2. Case 1 and 3 were born IUGR and presented in neonatal age group with complains of lethargy, reluctance to feed, failure to thrive and polyuria, while case 2 presented at 4 months of age with nephrocalcinosis. Initial bone profile in all cases revealed marked hypercalcemia (20.4-23.1 mg/dl), low phosphate (1.2-2.2 mg/dl), normal magnesium (2.3-2.4 mg/dl), raised alkaline phosphatase (>400 IU/L), strikingly high PTH (642-1077 pg/ml), low normal 25OH vitamin D level (16.7-20.9 ng/ml), high urine calcium to creatinine ratio (>0.20) and skeletal survey showed reduced bone density. After initial stabilization with hyperhydration and Pamidronate, trial of cinacalcet was given. Cinacalcet was started with dose of 1mg/kg/day and was gradually increased to 3mg/kg/day. None of our case responded to cinacalcet and needed repeated pamidronate infusion to optimize calcium level. Parathyroidectomy was planned in all. Cases 1 and 2 underwent successful parathyroidectomy (3 and half parathyroid removed and half implanted in sternocleidomastoid) with smooth Post-operative recovery and bone profile showing normal calcium, phosphate and PTH. Case 3 had a sad demise before surgery due to hospital acquired infection.

Conclusion: NSHPT is a rare disorder due to CASR gene mutation that is often underdiagnosed due to lacking genetic facilities in resource limiting countries. We are reporting 3 cases of CASR mutation (1 novel mutation) which did not respond to cinacalcet and two of them ended up in parathyroidectomy. We believe efficacy of cinacalcet in NSHPT due to CASR needs further randomized control trial.

Volume 94

59th Annual ESPE (ESPE 2021 Online)

22 Sep 2021 - 26 Sep 2021

European Society for Paediatric Endocrinology 

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