Mouly C1, Vargas-Poussou R2, Lienhardt A3, Silve C4, Hureaux M2, Magdelaine C5, Buffet A1, Grunenwald S1, Marc Kuhn J6, Brue T7, Reznik Y8, Tabarin A9, Martin-Coignard D10, Haymann JP11, Tack I12, Bennet A, Caron P1, Linglart A13, Vezzosi D1; Reference Centre for Rare Diseases of Calcium and Phosphate Metabolism.
Clin Endocrinol (Oxf). 2020 Apr 29. doi: 10.1111/cen.14211. [Epub ahead of print]
Familial hypocalciuric hypercalcaemia type 1 (FHH1), related to heterozygous loss-of-function mutations of the Calcium Sensing Receptor gene, is the main differential diagnosis for primary hyperparathyroidism. The aim of our study was to describe clinical characteristics of adult patients living in France with a genetically confirmed FHH1. DESIGN AND PATIENTS: This observational, retrospective, multicentre study included 77 adults, followed up in 32 clinical departments in France, with a genetic FHH1 diagnosis between 2001 and 2012.
Hypercalcaemia was diagnosed at a median age of 53 years [IQR: 38-61]. The diagnosis was made after clinical manifestations, routine analysis or familial screening in 56, 34 and 10% of cases, respectively, (n=58; data not available for 19 patients). Chondrocalcinosis was present in 11/51 patients (22%), bone fractures in 8/56 (14%) and renal colic in 6/55 (11%). The median serum calcium was 2.74 mmol/L [IQR: 2.63-2.86 mmol/L], the median plasma parathyroid hormone level was 4.9 pmol/L [3.1-7.1] and the median 24-hour urinary calcium excretion was 2.8 mmol/24 h [IQR: 1.9-4.0]. Osteoporosis (dual X-ray absorptiometry) or kidney stones (renal ultrasonography) were found in 6/38 patients (16%) and 9/32 patients (28%), respectively. Fourteen patients (18%) underwent parathyroid surgery; parathyroid adenoma was found in 3 patients (21%) and parathyroid hyperplasia in 9 patients (64%). No correlation between genotype and phenotype was established.
This large cohort study demonstrates that FHH1 clinical characteristics can be atypical in 33 patients (43%). Clinicians should be aware of this rare differential diagnosis in order to adopt an appropriate treatment strategy.