Endocrine Abstracts

Case: A 25-year-old male with a history of Asperger’s syndrome, not on regular medication, with no family history of endocrinopathy; was referred with mild hypercalcaemia found during routine investigations for fatigue, weight loss, diarrhoea and vomiting. A normal PTH suggested PTH-dependent hypercalcaemia. There was no history of fractures or nephrolithiasis. DEXA scan showed normal bone mineral density (femur, spine and forearm). The gastrointestinal symptoms and fatigue were investigated with a full blood count, biochemical profile, coeliac screen, faecal calprotectin, short Synacthen test and CT thorax/abdomen/pelvis which were all normal. In a vitamin D replete state, the 24-hour urinary calcium: creatinine excretion ratio was 0.0043, pointing to a diagnosis of FHH and genetic sequencing analysis of FHH related mutations returned heterozygous for AP2S1 (Arg15His), confirming a diagnosis of FHH3.

Discussion: FHH is a rare (1 in 78000), autosomal dominant (AD) and PTH dependent cause of hypercalcaemia. It is classified into three types based on inactivating mutations of CaSR, GNA11 and APS2S1 resulting in FHH1, FHH2 and FHH3, respectively.[1] FHH3 is associated with variable learning disabilities and behavioural difficulties[2] and can be misdiagnosed as Asperger’s syndrome or other neurodevelopmental disorders.

Conclusion: Consider FHH3 in young patients with cognitive dysfunction and hypercalcaemia.

References: 1. Lee, J.Y. and D.M. Shoback, Familial hypocalciuric hypercalcemia and related disorders. Best Pract Res Clin Endocrinol Metab, 2018. 32(5): p. 609-619.

2. Chinoy A, Skae M., Nicholson J, Mughal Z, Padidela R., Variable learning disability and behavioural difficulties in children with familial hypocalciuric hypercalcaemia type 3,, in 8th International Conference on Children’s Bone Health. 2017: Germany.