Table 2 Main differential diagnoses of calcium disorders related to CASR gene mutations

Hypercalcaemia

Familial hypocalciuric hypercalcaemia (FHH) syndromes

- type 2 via mutations of the GNA11 gene (10%)

- type 3 via mutations of the AP2S1 gene (15%)

- via mutations of other as of yet unknown genes (20%)

Familial hyperparathyroidism

- via mutations of tumour suppressor genes:

o MEN1 (Multiple endocrine neoplasia type 1)

o HRPT2 (/CDC73)

o CDKN1B (MEN4)

o but also the APC, SFRPs, GSK3β, RASSF1A, HIC1, RIZ1, and WT1 genes, and possibly CASR, GNA11, AP2S1, and GCM2…

- via mutations of proto-oncogenes (CCND1/PRAD1, RET [MEN2], ZFX, CTNNB1, EZH2)cpe

Hyperparathyroidism with normal or low PTH with hypercalciuria via mutation of the genes

- CYP24A1

- SLC34A1

Hypercalcemia associated with reduced glomerular filtration rate, making the low urine calcium difficult to interpret

Hypocalcaemia

Hypercalciuric hypocalcaemia syndrome type 2 via activating mutation of the GNA11 gene.

No gain-of-function mutation described for the AP2S1 gene

Other types of hypoparathyroidism