Hypocalcaemic Disorders, Hypoparathyroidism, and Pseudohypoparathyroidism

Abstract

Hypocalcaemia ranges from an asymptomatic biochemical abnormality to a life-threatening disorder, and may be caused by vitamin D deficiency, chronic renal failure, hypomagnesaemia, hypoparathyroidism, and pseudohypoparathyroidism. Hypoparathyroidism may occur as part of a pluriglandular autoimmune disorder or a complex congenital defect, such as the autosomal dominant DiGeorge or Hypoparathyroidism-deafness-renal anomalies (HDR) syndromes. In addition, hypoparathyroidism may occur as an isolated endocrinopathy, with autosomal dominant, autosomal recessive, and X-linked inheritances. Molecular genetic studies of hypoparathyroidism have elucidated important roles for: transcription factors (e.g. TBX1, GATA3, GCMB, and AIRE), the tubulin-specific chaperone (TBCE), and the mitochondrial genome in determining parathyroid development and function; the calcium-sensing receptor (CaSR) and G-protein subunit α‎-11 (Gα‎11) in regulating extracellular calcium and parathyroid hormone (PTH) secretion; and PTH gene expression for synthesis and secretion of PTH. Pseudohypoparathyroidism, an autosomal dominant disorder associated with PTH resistance, is due to abnormalities of Gα‎s, which mediates PTH1 receptor signalling.