Endocrine Abstracts

Autosomal dominant hypocalcemia (ADH) is a rare cause of hypocalcemia 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 3.8pmol/l, RI 1.6-6.9; vitamin D 42nmol/l). She had been investigated elsewhere, where it was deemed idiopathic. 24 hr calcium excretion 3.1mmol. Genetic testing: heterozygous mutation in CASR (Ala785Vals), confirming ADH Type 1 (ADH1). Her son (12 years old), 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 1.8pmol/l, RI 1.6-6.9; vitamin D 70nmol/l). 24 hr calcium excretion 6.1mmol. Genetic testing: heterozygous mutation in GNA11 (Arg60Cys), confirming ADH Type 2 (ADH2). Neither patient experienced renal calculi, fractures, or dental abnormalities; however, P1 has a small (4mm) intracalyceal calcification on ultrasound. The ADH Type 1 phenotype is better described than that of ADH Type 2; 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, but in the absence of formal recommendations, follow-up for ADH Type 2 is similar to that for ADH Type 1. Our cases add to the literature on ADH Types 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.