Endocrine Abstracts

A 65 year old patient who was hospitalised for a reactive arthritis of the knee due to Rickettsia infection, presented an asymptomatic persistant chronic hypocalcemia and hyperphosphoremia. In her medical history, we noted a hypertension treated with amlodipine and bisoprolol, syndrome of sleep apnoea, acquired lumbar spinal canal stenosis and sequelae of poliomyelitis acquired at 10 years of age in Congo, her place of origin. According to her blood test results, total calcium levels were low between 1,9 to 2,1 mmol/l (normal ranges 2,15–2,50), phosphorus levels high between 1,61 to 1,81 mmol/l (normal ranges 0,81–1,45), albumine levels normal between 34 to 42 g/l (normal ranges 34–48), parathormone levels abnormaly normal between 17 to 55 ng/l (normal ranges 15–65), 25OH-vitamine-D levels low to normal between 22 to 44 mg/l (normal ranges 30–60). Urinairy calcium excretion between 0,022 to 0,081 mol/mol creat (normal range <0,700). Renal function was normal with creatinine levels between 0,40 to 0,75 mg/dl (normal range 0,55–0,96). The diagnosis of hypoparathyroidism was evoked with suspicion of an activating mutation of the calcium-sensing receptor (CaSR) gene. We performed a citrate infusion test to provoke more pronounced hypocalcemia by administrating intravenously a continuous perfusion of 100 ml solution of dextrose 2.45 g, sodium citrate 2.2 g and citric citrate 0.7 g, for 30 minutes. The subsequent measures of total calcium, ionised calcium and parathormone every 10 minutes from T0 to T30 min, showed no increase of parathormone levels in response to provoked hypocalcemia. The genetic analysis didn’t identify any mutation but identified a novel variant c.2192G>A (p.Cys731Tyr) of the CaSR gene. This variant has not been described in the literature before and results from the In-Silico analysis are contradictory, benign for Polyphen and pathogenic for MutationTaster and SIFT. A genetic family study could have helped us to better interpret this result, but unfortunately the patient lives alone in Belgium since 2015 and all her family lives in Africa. Thus, the pathogenic nature of this novel variant of CaSR gene remains unknown for the time being and the variant is classified as class III.

References: 1. Rate and concentration dependence of parathyroid hormone dynamics during stepwise changes in serum ionized calcium in normal humans. Grant et al. J Clin Endocrinol Metab 1990;71:370–8.

2. Citrate infusion test in the diagnosis of hypocalcemia due to a mutation in the calcium-sensing receptor gene. Poppe et al. Eur J Intern Med 2002;13(4):276–279