Clinical and genetic insights into Autosomal Dominant Hypocalcemia type 1: a single-center case series including genotype-phenotype correlations, pregnancy outcomes, and novel CASR variants
Abstract
PURPOSE: The main purpose of this study was to provide a comprehensive characterization of adult patients with Autosomal Dominant Hypocalcemia type 1 (ADH1), focusing on clinical and biochemical features, with particular attention to renal involvement, skeletal features and ectopic calcifications. The secondary aims were to explore potential genotype-phenotype correlations, describe two previously unreported CASR variants, and report pregnancy outcomes in affected women.
METHODS: We conducted a retrospective, single-centre study of 11 adults with genetically confirmed ADH1 followed at a tertiary Endocrinology Unit between March 2012 and May 2025. Clinical presentation, biochemical data, renal and cerebral involvement, skeletal status and treatment history were collected at first evaluation and during follow-up. CASR variants were identified by next-generation sequencing with Sanger confirmation, and genotype-phenotype relationships were explored.
RESULTS: At diagnosis, 64% of patients reported hypocalcemia-related symptoms, while 36% were asymptomatic. Nephrolithiasis, nephrocalcinosis and basal ganglia calcifications were frequent, in patients exposed to long-term calcium and active vitamin D therapy, although causal relationships cannot be established. Axial BMD was normal or increased, whereas radial BMD was often reduced and bone turnover markers were low-normal; no fragility fractures were documented. We identified two novels CASR missense variants and observed marked…
How strong is the evidence?
Evidence Hub reads this as a case series, done in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health. Reported size: 11 participants or records.
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