Endocrine Abstracts (2015) 38 P12 | DOI: 10.1530/endoabs.38.P12

Familial hypocalciuric hypercalcaemia due to AP2S1 mutation in a patient with failed parathyroidectomies: a case report

Eswari Chinnasamy, Paul Hurley, Katie Snape & Gul Bano


St George’s University Hospitals NHS Trust, London, UK.


Familial hypocalciuric hypercalcaemia (FHH) is a rare condition and can be mistaken for primary hyperparathyroidism (PHPT). Distinguishing this from the later is vital to avoid un-necessary surgery as this is a benign condition. Ca:Cr excretion ratio >0.01 in a spot urine is widely used to rule out FHH. However this was calculated from 24 h urine samples on the original studies.

We present a case of 46-year-old lady who presented with symptomatic hypercalcaemia, initially diagnosed as PHPT. Peak C.Ca was 2.78 with low normal PO4, and normal PTH, 5.7 pmol/l. USG and SestaMIBI were suggestive of possible left inferior parathyroid adenoma. Cortical bone mineral density was normal on DEXA. Initial urine Ca:Cr excretion ratio was 0.04. Following surgery she had persistent hypercalcaemia (C.Ca 2.93 mmol/l) and histology showed normal parathyroid tissue. Repeat SestaMIBI was negative and MRI neck showed a possible left parathyroid adenoma. Second surgery also failed, histology confirmed normal parathyroid tissue. However patient improved symptomatically after second surgery in spite of persistent hypercalcaemia. A 24 h urine calcium was low at 1.58 and subsequent genetic analysis confirmed FHH type 3 with mutation in AP2S1 gene (c.43C>T_p.Arg15Cys). Most cases of FHH are due to mutation in calcium-sensing receptor (CaSR) gene mutation (>65%) and in the rest, AP2S1 mutation accounts for more than 20%. Disease causing mutation in this gene was first described in two unrelated kindreds by Nebit et al. (1), presented in BES 2013. It is not uncommon for these patients to have undergone parathyroid surgery in the literature. With lack of data on true prevalence of FHH, it is likely that some of these patients are misdiagnosed as PHPT. Low 24 h urine calcium, normal cortical density, and hypermagnaesemia are useful clues in addition to positive family history to make a correct diagnosis.

Reference: 1. Nesbit MA, Hannan FM, Howles SA, et al. Mutations in AP2S1 cause familial hypocalciuric hypercalcemia type 3. Nat Genet 2013 45 93–97.

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