Familial isolated hypoparathyroidism

Familial isolated hypoparathyroidism (FIH) is a rare inherited endocrine disorder characterized by low or absent parathyroid hormone (PTH) production without other associated syndromic features. Unlike hypoparathyroidism that occurs as part of broader syndromes (such as DiGeorge syndrome or autoimmune polyendocrinopathy), FIH occurs in isolation, affecting only the parathyroid glands. The condition leads to hypocalcemia (low blood calcium) and hyperphosphatemia (elevated blood phosphorus), which can cause a wide range of symptoms affecting the neuromuscular and skeletal systems. Key clinical features include muscle cramps, tingling and numbness in the hands, feet, and around the mouth (paresthesias), muscle spasms (tetany), and seizures — all resulting from low calcium levels. In severe neonatal or infantile forms, life-threatening hypocalcemic seizures may occur shortly after birth. Chronic hypocalcemia can lead to calcification of the basal ganglia in the brain, cataracts, dental abnormalities, and impaired kidney function. The severity and age of onset vary depending on the specific genetic cause. FIH can be caused by mutations in several genes, including GCM2 (glial cells missing homolog 2), PTH (parathyroid hormone gene), and CASR (calcium-sensing receptor gene, typically gain-of-function mutations). The inheritance pattern varies accordingly — autosomal dominant, autosomal recessive, or X-linked recessive forms have all been described. Treatment consists of lifelong supplementation with calcium and active vitamin D analogs (such as calcitriol or alfacalcidol) to maintain serum calcium levels within a safe range. Recombinant PTH (rhPTH 1-84) has also been approved for chronic hypoparathyroidism in adults and may be used in refractory cases. Regular monitoring of calcium, phosphorus, kidney function, and urinary calcium excretion is essential to prevent complications such as nephrocalcinosis and kidney stones.

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