The calcium-sensing receptor (CaSR) plays a pivotal role in systemic calcium metabolism by regulating parathyroid hormone secretion and urinary calcium excretion. The diseases caused by an abnormality of the CaSR are genetically determined or are more rarely acquired. The genetic diseases consist of hyper- or hypocalcemia disorders. Hypercalcaemia disorders are related to inactivating mutations of the CASR gene either heterozygous (autosomal dominant familial benign hypercalcaemia, still named hypocalciuric hypercalcaemia syndrome type 1) or homozygous (severe neonatal hyperparathyroidism). The A986S, R990G and Q1011E variants of the CASR gene are associated with higher serum calcium levels than in the general population, hypercalciuria being also associated with the R990G variant. The differential diagnosis consists in the hypocalciuric hypercalcaemia syndrome, types 2 (involving GNA11 gene) and 3 (involving AP2S1 gene); hyperparathyroidism; abnormalities of vitamin D metabolism, involving CYP24A1 and SLC34A1 genes; and reduced GFR. Hypocalcemia disorders, which are more rare, are related to heterozygous activating mutations of the CASR gene (type 1), consisting of autosomal dominant hypocalcemia disorders, sometimes with a presentation of pseudo-Bartter’s syndrome. The differential diagnosis consists of the hypercalciuric hypocalcaemia syndrome type 2, involving GNA11 gene and other hypoparathyroidism aetiologies. The acquired diseases are related to the presence of anti-CaSR antibodies, which can cause hyper- or especially hypocalcemia disorders (for instance in APECED syndromes), determined by their functionality. Finally, the role of CaSR in digestive, respiratory, cardiovascular and neoplastic diseases is gradually coming to light, providing new therapeutic possibilities. Two types of CaSR modulators are known: CaSR agonists (or activators, still named calcimimetics) and calcilytic antagonists (or inhibitors of the CasR). CaSR agonists, such as cinacalcet, are indicated in secondary and primary hyperparathyroidism. Calcilytics have no efficacy in osteoporosis, but could be useful in the treatment of hypercalciuric hypocalcaemia syndromes.

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Introduction. The diagnosis of non-HIV lipodystrophies is challenging, especially since borderline forms with type 2 diabetes have been described (Strickland Diabetes Care 2013).Aim: to identify the most specific anthropometric and biological parameters enabling to differentiate lipodystrophic from obese and control subjects.Methods. This prospective study (clin.gov 2009-AO-1169-48) included 94 patients divided in 3 groups adjusted for age and gender: 52 lipodystrophic patients (among whom 16LMNA–mutated lipodystrophies (LDM),16non-LMNAmutated partial lipodystrophies (LDNM), and 20 other types of lipodystrophies), 28 obese (O; 12 diabetic (OD) and 16 non-diabetic (OND)) and 14 normal-weighed healthy subjects (C). The anthropometric (DEXA, MRI) characteristics and leptin levels of the patients were recorded. Three ratios were calculated to assess the respective part of fat and lean mass (FM/LM), intra- and whole abdominal fat (IAF/WAF) and adipose tissue function (leptin/WAF).Results. The three groups differed by the FM, LM, IAF, WAF, leptinemia, trunk FM/LM (P<0.0001), IAF/WAF (P<0.001) and leptin/WAF (P<0.01). The main distinctive feature of LDM compared to C was IAF (188±38vs 82±23 cc;P<0.01) whereas BMI, FM, LM, WAF and leptinemia were similar. The ratios ranges of the five subgroups were as follows: IAF/WAF: 0.5 in LDMvs0.3 in all other subgroups; trunk FM/LM: 0.2 in LDM and C, increased from 0.5 to 0.7 and 0.8 respectively in LDNM, OD, OND); leptin/WAF: decreased to 2.3 and 1.6 in respectively LDM and LDNM compared to C (2.7), and increased in OD (3.7) and OND (5.6).Conclusion. Increased intra/whole abdominal fat ratio, hypoleptinemia and preserved fat/lean mass ratio characterized lipodystrophic laminopathies, in contrast with obese people who showed an increased fat/muscle mass, hyperleptinemia and preserved intra/whole abdominal fat ratio. Non-mutated lipodystrophic patients were intermediate, with decreased leptin/WAF ratio, close to LDM, and increased IAF/WAF and FM/LM ratios close to the obese population.

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