A novel homozygous mutation in the parathyroid hormone gene (PTH) in a girl with isolated hypoparathyroidism.

Case Report: A female patient with consanguineous parents presented with severe symptomatic hypocalcemia (1.62mmol/l) at the age of 4 months. Treatment with oral 1,25-(OH)2-vitamin D and calcium carbonate was started and serum calcium concentrations were stabilized at the lower end of the normal range. Subsequently she developed normally and had no evidence for additional abnormalities. Over the next 6 years of observation, serum levels of PTH were always low but detectable (5.3-2.5pg/ml; normal: 15-65pg/ml) resulting in the diagnosis of isolated hypoparathyroidism. Disturbances in the vitamin-D metabolism, autoimmune polyendocrine syndrome (APS), chromosomal anomalies or mutations in the calcium-sensing receptor gene (CaSR) were excluded. Nucleotide sequence analysis of PTH revealed the presence of a homozygous point mutation (c.68C>A) in exon 2 that introduces a premature termination codon (p.Ser23X in the Pre- sequence of PTH) resulting in a non-functional PTH-precursor.

Conclusion: A novel, homozygous PTH mutations was identified, which is obviously a very rare cause of isolated hypoparathyroidism (IHP). Although activating CaSR mutations are the most common cause of hypoparathyroidism, analysis of the PTH gene should be considered in those IHP patients in whom a CaSR has been excluded, particularly if the parents are likely to be consanguineous.