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Endocrine Abstracts (2019) 65 P86 | DOI: 10.1530/endoabs.65.P86

SFEBES2019 POSTER PRESENTATIONS Bone and calcium (51 abstracts)

Effect of vitamin D analogue therapy in a patient with autosomal dominant hypocalcaemia type 2 (ADH2) due to GNA11 p.Arg60Leu mutation

Catriona Farrell 1 , Fadil Hannan 2 , Jacob George 3 , Emma Robinson 4 , Joanne McLean 5 , Hannah Boon 6 , Treena Cranston 6 , David Goudie 5 , Rajesh Thakker 7 & Paul Newey 1


1Division of Molecular and Clinical Medicine, Ninewells Hospital & Medical School, University of Dundee, Dundee, UK; 2Nuffield Department of Women’s and Reproductive Health, University of Oxford, Oxford, UK; 3Ninewells Hospital & Medical School, University of Dundee, Dundee, UK; 4University Hospitals of Derby & Burton NHS foundation Trust, Derby, UK; 5Clinical Genetics, Ninewells Hospital & Medical School, University of Dundee, Dundee, UK; 6Oxford Medical Genetics Laboratory, Oxford University Hospitals NHS Foundatiion Trust, Oxford, UK; 7Radcliffe Department of Medicine, University of Oxford, Oxford, UK


Background: Autosomal dominant hypocalcaemia (ADH) is most commonly due to activating mutations in the Calcium Sensing Receptor (ADH Type 1), in which treatment with vitamin D analogues is frequently associated with hypercalciuria. More recently, activating mutations in the alpha-subunit of the G-protein α-11 (Gα11), encoded by GNA11, have been identified in a small number of ADH kindreds (ADH Type 2). The impact of vitamin D analogue treatment in ADH2 patients has not been evaluated.

Case Report: The proband, a 46-year-old female, was incidentally found to be hypocalcaemic. Clinical assessment revealed that she was experiencing intermittent paresthesia and cramping of the digits. Baseline biochemical testing confirmed a reduced serum corrected calcium (1.79 mmol/l; NR 2.1–2.55 mmol/l), raised serum phosphate (2.05; NR 0.8–1.5 mmol/l), low plasma PTH (1.0 pmol/l; NR 1.5–7.6 pmol/l), and low urine calcium:creatinine (U.Ca:Creat) ratio (0.2; NR 0.3–0.7). Her father had been on long-term calcium supplementation raising the possibility of a dominantly inherited hypocalcaemic disorder. Subsequent gene-panel testing revealed a pathogenic GNA11 variant (c.179G>T; p.Arg60Leu) establishing the diagnosis of ADH2. The patient was treated with calcitriol (with ≥1000 mg dietary/oral calcium/day) to relieve hypocalcaemic symptoms and has been monitored for >21 months with serum and urine calcium measurements. The calcitriol dose was progressively increased from 250 ng daily to 1000 ng daily, which improved symptoms, and increased her serum calcium in a dose-dependent manner from 1.79 to 2.09 mmol/l. This was not associated with consistent alterations in serum phosphate or PTH. However, treatment with calcitriol 1000 ng daily increased her U.Ca:Creat ratio to 0.5 and was associated with hypercalciuria (24 hour urine calcium >0.1 mmol/kg per 24 h), despite failing to normalise serum calcium concentration.

Conclusions: Although vitamin D analogue therapy may alleviate symptoms and improve hypocalcaemia in patients with ADH2, caution is required as hypercalciuria may occur, even when serum calcium is below the reference range.

Volume 65

Society for Endocrinology BES 2019

Brighton, United Kingdom
11 Nov 2019 - 13 Nov 2019

Society for Endocrinology 

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