Endocrine Abstracts

A 13-year-old girl with a history of developmental dyspraxia, enamel hypoplasia and a raised creatinine kinase (CK) presented to her GP with fatigue on any physical exertion including walking. On questioning she has always complained of muscle pain and tiring easily since she was a young child. On blood testing it was identified that she was profoundly hypocalcaemic with a calcium adjusted for albumin of 1.52 mmol/l, phosphate of 3.20 mmol/l, parathyroid hormone (PTH) of 1.5 pmol/L and a of CK of 363 U/l. From these results she was diagnosed with autoimmune hypoparathyroidism and referred to a paediatric endocrinologist. She was prescribed 1-alpha-hydroxycholecalciferol, but despite treatment, and compliance there was no significant increase in the calcium or decrease in the CK. As the hypoparathyroidism was not the cause of the low calcium a number of other tests were conducted, until a calcium sensing mutation was suggested. DNA analysed showed that there was a T to C nucleotide substitution in exon 7 of the CASR gene (c.2495T>C), which is predicted to result in the replacement of the amino acid phenylalanine with serine at residue 832. This substitution is a change from an aromatic hydrophobic amino acid to an uncharged polar amino acid and is believed to be highly pathogenic. The resulting autosomal dominant hypocalcaemia causes inappropriate inhibition of PTH secretion and renal calcium absorption, due to the increased sensitivity of the calcium receptor expressed in both the parathyroids and the kidneys, resulting in hypocalcaemia. To treat this condition PTH injections have been offered, but have been rejected. The present treatment is with vitamin D, calcium and diuretics with frequent ultrasounds to monitor nephrocalcinosis. Both parents have had their calcium levels checked and both siblings are also unaffected therefore this is considered to be a de novo mutation.