Infantile hypercalcemia type 1 (HCINF1): a rare disease resulting in nephrolithiasis and nephrocalcinosis caused by mutations in the vitamin D catabolic enzyme, CYP24A1

• Published in: Journal of endocrinological investigation Vol. 47; no. 11; pp. 2663 - 2670
• Main Authors: Jones, G., Kaufmann, M., St-Arnaud, R.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.11.2024
• Subjects: Endocrinology; Humans; Hypercalcemia - diagnosis; Hypercalcemia - genetics; Internal Medicine; Medicine; Medicine & Public Health; Metabolic Diseases; Mutation; Nephrocalcinosis - diagnosis; Nephrocalcinosis - etiology; Nephrocalcinosis - genetics; Nephrolithiasis - etiology; Nephrolithiasis - genetics; Short Review; Vitamin D - metabolism; Vitamin D3 24-Hydroxylase - genetics; Hypercalcemia; Nephrocalcinosis; CYP24A1; Nephrolithiasis; HCINF-type 1; Vitamin D
• ISSN: 1720-8386; 1720-8386
• DOI: 10.1007/s40618-024-02381-8

Infantile hypercalcemia type 1 (HCINF1), formerly known as Lightwood syndrome, is a subtype of hypercalcemia caused by loss-of-function biallelic mutations in the vitamin D catabolic enzyme, CYP24A1, which 24-hydroxylates the hormone 1,25-(OH) 2 D 3 . This short review focuses on the main features of the HCINF1 disease; emerging knowledge of the structure and function of the cytochrome P450, CYP24A1 and the location of inactivating mutations; the development of a rapid LC–MS/MS-based laboratory test for defective 24-hydroxylation; and future implications for bioanalytical assay and treatment of all types of vitamin D-related hypercalcemic conditions.