Familial isolated hypoparathyroidism (FIH) is a rare heterogeneous group of metabolic disorders characterized by abnormal calcium metabolism due to deficient secretion of parathormone (PTH), without other endocrine disorders or developmental defects. It can occur at any age (from the newborn period to adulthood) but generally starts within the first decade of life. The clinical signs are mainly those of hypocalcemia: myopathy, muscular weakness, cramps, tetany, lenticular cataracts, teeth anomalies and short stature. Isolated hypoparathyroidism may be sporadic or familial, with autosomal dominant or recessive inheritance. FIH may be due to an activating mutation of the calcium-sensing receptor (CASR) gene. This is the most common cause of genetic hypoparathyroidism and is transmitted as an autosomal dominant trait. It represents 42% of isolated hypoparathyroidism cases. Thirteen mutations have been described in familial or sporadic cases. In three families, mutations in the PTH gene have been identified. This type of FIH is transmitted as an autosomal recessive or dominant trait. One family has been reported with a mutation in the gene encoding the glial cells missing homolog b (GCMB) transcription factor. In this case, transmission is autosomal recessive. Diagnosis is made when hypocalcemia, hyperphosphoremia, and low or undetectable PTH levels are observed. Management consists of symptomatic treatment with supplementary calcium and vitamin D.
Last update: February 2005