Endocrine Abstracts

Autosomal dominant hypocalcemia (ADH) is a rare cause of hypocalcaemia that should be considered when no other cause is evident. We describe two patients in whom a diagnosis of ADH was made following appropriate biochemical and genetic investigation. P1 was referred with known, asymptomatic, hypocalcaemia (calcium 2.03mmol/l, RI 2.2-2.6; PTH 3.8 pmol/l, RI 1.6-6.9; vitamin D; ⁴² nmol/l), previously deemed idiopathic. 24 hour calcium excretion 3.1mmol. Genetic testing: heterozygous mutation in CASR (Ala785Vals), confirming ADH Type 1 (ADH1). Her son (12), was later confirmed to have the mutation. P2 was referred for investigation of asymptomatic hypocalcaemia (calcium 2.03mmol/l, RI 2.2-2.6; PTH 1.8 pmol/l, RI 1.6-6.9; vitamin D; ⁷⁰ nmol/l). 24 hour calcium excretion 6.1mmol. Genetic testing: heterozygous mutation in GNA 11 (Arg60Cys), confirming ADH Type 2 (ADH2). Neither patient experienced renal calculi, fractures, dental abnormalities, however P 1 has a small (4mm) intracalyceal calcification on ultrasound. ADH Type 1 phenotype is better described; levels of calcium probably remain stable over time, however nephrolithiasis and nephrocalcinosis can develop at any stage, so periodic renal imaging is recommended. Seizures and basal ganglia calcification can also occur. Long term monitoring is recommended. The ADH Type 2 phenotype is not fully elucidated. In the absence of formal recommendations, follow up for ADH 2 is similar to that for ADH 2. Our cases add to the literature on ADH 1 and 2 and reinforce the need to perform further investigation, even in asymptomatic individuals, if the biochemical profile cannot be explained. Genetic diagnoses allow appropriate follow up and cascade testing, where desired.