Endocrine Abstracts

Autosomal dominant hypocalcemia type 1 (ADH1) is a genetic disorder characterized by low serum calcium and low or inappropriately normal levels of PTH. It is caused by a heterozygous activating mutation of the calcium-sensing receptor (CASR) gene, resulting in decreased sensitivity of the receptor to low serum calcium. The aim of our study was to describe a series of patients with ADH1 followed at our outpatient clinic from 2011 to 2023. A total of 7 patients (4 females and 3 males) carrying a missense variant of the CASR gene, were collected. Median age at diagnosis was 46 years (IQR 35-50), with only one patient diagnosed at birth. Two probands (71.4%) belonged to two kindreds with ADH1 and two (28.6%) were sporadic cases. Four patients (57%) were symptomatic at the time of the diagnosis (2 had recurrent kidney stones, 2 had cramp-like muscle pain with paresthesias and one recurrent hypocalcemic seizures since childhood). The remaining three patients were asymptomatic. At the time of our first evaluation, all patients had median albumin-corrected serum calcium of 7.72 mg/dl (IQR 6.9-8.1), PTH 17 ng/ml (IQR 15.5-20.7), phosphate 3.4 mg/dl (IQR 3.25-4.75), magnesium 1.9 mg/dl (IQR 1.68-2.0), creatinine 0.85 mg/dl (IQR 0.70-1.12), eGFR 90.8 mg/ml (89-105) and 24-h urinary calcium 202 mg IQR 179-225). Only one patient was on therapy with calcium carbonate, alfacalcidol and magnesium. Four of seven patients (57 %) had at least one target organ involvement (bilateral nephrolithiasis in three, nephrocalcinosis in four and reduced eGFR in two). One of six patients (17%) with available brain CT scan had basal ganglia calcifications. Bone mineral density at lumbar spine, femur and 1/3 distal radius was normal in five and low in two (median BMD 0.69; Z-score -2.2) at 1/3 distal radius. One patient started treatment with calcium carbonate and calcitriol and one also teriparatide. The median follow-up after our first evaluation was 5 years (IQR 4-8) and available only in five patients. Of the two patients on therapy, the median albumin-corrected serum calcium concentration was 8.9 mg/dl (IQR 8.9-8.9), phosphates 3.55 mg/dl (IQR 3.23-3.78), magnesium 1.85 mg/dl (IQR 1.77-1.92) and 24-h urinary calcium 345 mg/24 h (IQR 322-367). The three patients who were not on therapy had median values of serum calcium of 8.1 mg/dl (8.05-8.1), phosphate 3.85 mg/dl (3.78-3.92) and magnesium 1.9 mg/dl (1.85-1.95). Our data confirm a variable phenotype of ADH1 ranging from asymptomatic to mild-severe symptomatic profile.