Case report: A Newly Identified G-protein Subunit α-11 Loss-of-Function Variant Causing Familial Hypocalciuric Hypercalcemia Type 2 in an Italian Kindred.

Background: FHH2 is the rarest subtype of familial hypocalciuric hypercalcemia disorders affecting the CaSR signaling pathway. It is caused by heterozygous loss-of-function mutations in the Case description: We report the case of a 39-year-old man referred to our outpatient clinic for a non-toxic multinodular goiter. During biochemical examination, mild hypercalcemia with normal PTH levels and low urinary calcium excretion (calcium-creatinine clearance ratio< 0.01) was detected. He had no evidence of kidney stones or nephrocalcinosis and demonstrated normal bone mineral density at dual-energy X-ray absorptiometry. A similar biochemical profile in his mother suggested FHH. Following total thyroidectomy for the goiter, the patient's calcium and PTH levels normalized. Genetic testing identified a novel heterozygous germline frameshift variant in Conclusions: In this report, we describe the eighth FHH2 kindred and highlight the biochemical heterogeneity of this rare condition. Our findings demonstrate that the normalization of serum calcium during follow-up does not necessarily exclude the diagnosis. Furthermore, we underscore the clinical importance of integrating genetic findings with longitudinal biochemical data.