Novel Gene Mutation Causes Persistent Hypercalcemia in Young Adult

This case report describes a challenging diagnosis of hypercalcemia in a young adult that reveals important insights into rare genetic causes of calcium metabolism disorders. The discovery of a novel gene variant expands our understanding of how genetic defects can cause lifelong health complications.

Researchers investigated a 26-year-old man who developed severe headaches and hypertension after taking high-dose vitamin D supplements. Laboratory tests revealed persistent hypercalcemia (elevated blood calcium) and kidney stones, but standard causes like hyperparathyroidism and cancer were ruled out. Genetic analysis identified a previously unknown homozygous mutation in the CYP24A1 gene.

The CYP24A1 gene produces an enzyme called 24-hydroxylase that breaks down active vitamin D (1,25-dihydroxyvitamin D3) into inactive metabolites. When this gene is defective, active vitamin D accumulates, causing excessive calcium absorption from the intestines and leading to hypercalcemia and kidney stone formation. This condition, known as idiopathic infantile hypercalcemia, typically presents in infancy but can remain undiagnosed until adulthood.

Treatment with fluconazole (an antifungal medication) successfully reduced calcium levels from 12.7 mg/dL to 9.4 mg/dL by inhibiting vitamin D synthesis. However, calcium levels rose again when treatment was discontinued, indicating the need for ongoing management. The patient also required psychiatric treatment for mood disorders potentially related to chronic hypercalcemia.

This case demonstrates the importance of considering genetic causes in unexplained hypercalcemia and suggests that targeted therapies like fluconazole may offer effective treatment options for this rare condition.