Endocrine Abstracts

Familial hypoparathyroidism is a rare condition. A family with seven affected individuals is described. Six sets of case notes were available for comparison. The most probable type of genetic transmission is autosomal dominant. There is also a family history of renal stones and ankylosing spondylitis.

At diagnosis, adjusted calcium levels ranged between 1.77 and 1.92 mmol/L. PTH levels were either undetectable or in the low-normal range. Most cases were symptomatic. 24 hour urinary calcium results are available for three patients. One was prior to commencing treatment and urinary calcium was just below the normal range at 3.42 mmol/day (3.5–7.5). In the younger generation, hypoparathyroidism was diagnosed at an earlier age due to screening.

It is likely that this is isolated familial hypoparathyroidism. One case has type 1 diabetes mellitus, but there is no other evidence of autoimmunity. There is no family history of deafness or renal cysts. Autosomal dominant causes of isolated familial hypoparathyroidism include PTH gene mutations and calcium-sensing receptor (CaSR) gene mutations. The PTH gene is located on chromosome 11p15. The CaSR gene is located on chromosome 3q13.3–q21. Inherited gain of function of CaSR is otherwise known as autosomal dominant hypocalcaemic hypercalciuria.

In AD hypocalcaemic hypercalciuria, the hypocalcaemia is usually less severe than idiopathic hypoparathyroidism. They usually have low or normal PTH levels. If asymptomatic, no treatment is required. However, symptoms may be severe. Treatment with vitamin D analogues may lead to hypercalciuria, nephrocalcinosis and renal impairment.

Knowledge of the mutation in this family is clinically important. If a CaSR gene abnormality was confirmed, then vitamin D dose reduction may be helpful. Screening for renal complications could be intensified.