常染色体優性低カルシウム血症1型：個別化治療の現状と将来展望

A 28-d-old female infant presented with clonic seizures secondary to hypocalcemia (calcium [Ca], 5.7 mg/dL) and hypoparathyroidism (intact parathyroid hormone [PTH], 7 pg/mL). Despite the initiation of oral alfacalcidol therapy, she experienced recurrent episodes of generalized convulsions or focal tetany, despite calcium lactate administration during febrile episodes. Her younger sister exhibited frequent irritability until day 38 of life due to hypocalcemia (Ca, 7.7 mg/dL) and hypoparathyroidism (intact PTH, 5 pg/mL). She experienced three febrile generalized seizures during infancy despite oral alfacalcidol treatment. Both sisters developed nephrocalcinosis despite oral hydrochlorothiazide treatment to reduce hypercalciuria. Genetic testing identified a pathogenic variant, c.2504C > A (p.Ala835Asp), in the calcium-sensing receptor (CASR) gene in both sisters. Their father carried the same variant but remained asymptomatic. This finding led to a diagnosis of autosomal dominant hypocalcemia type 1 (ADH1). Optimal active vitamin D treatment in ADH1 remains challenging because of difficulty maintaining stable serum Ca levels amid fluctuating physiological demands, as well as persistent hypercalciuria resulting from combined PTH deficiency and CaSR activation. Emerging therapies, including calcilytics, may help address these limitations.