Kidney function and influence of sunlight exposure in patients with impaired 24-hydroxylation of vitamin D due to CYP24A1 mutations

Am J Kidney Dis. 2015 Jan;65(1):122-6. doi: 10.1053/j.ajkd.2014.06.037. Epub 2014 Nov 4.


Loss-of-function mutations of CYP24A1, the enzyme that converts the major circulating and active forms of vitamin D to inactive metabolites, recently have been implicated in idiopathic infantile hypercalcemia. Patients with biallelic mutations in CYP24A1 present with severe hypercalcemia and nephrocalcinosis in infancy or hypercalciuria, kidney stones, and nephrocalcinosis in adulthood. We describe a cohort of 7 patients (2 adults, 5 children) presenting with severe hypercalcemia who had homozygous or compound heterozygous mutations in CYP24A1. Acute episodes of hypercalcemia in infancy were the first symptom in 6 of 7 patients; in all patients, symptoms included nephrocalcinosis, hypercalciuria, low parathyroid hormone (PTH) levels, and higher than expected 1,25-dihydroxyvitamin D levels. Longitudinal data suggested that in most patients, periods of increased sunlight exposure tended to correlate with decreases in PTH levels and increases in calcemia and calciuria. Follow-up of the 2 adult patients showed reduced glomerular filtration rate and extrarenal manifestations, including calcic corneal deposits and osteoporosis. Cases of severe PTH-independent hypercalcemia associated with hypercalciuria in infants should prompt genetic analysis of CYP24A1. These patients should be monitored carefully throughout life because they may be at increased risk for developing chronic kidney disease.

Keywords: 1,25-dihydroxyvitamin D (1,25[OH](2)D); 24α-hydroxylase; CYP24A1; chronic kidney disease (CKD); hypercalcemia; hypercalciuria; hypervitaminosis D; idiopathic infantile hypercalcemia (IIH); nephrocalcinosis; parathyroid hormone (PTH); vitamin D metabolism.

Publication types

  • Case Reports

MeSH terms

  • Bone Density Conservation Agents / pharmacology
  • Calcium / metabolism
  • Child
  • Child, Preschool
  • Diphosphonates / pharmacology*
  • Female
  • Fluid Therapy / methods*
  • Humans
  • Hypercalcemia* / genetics
  • Hypercalcemia* / physiopathology
  • Hypercalciuria / genetics
  • Hypercalciuria / physiopathology
  • Infant
  • Kidney Function Tests / methods
  • Male
  • Middle Aged
  • Monitoring, Physiologic / methods
  • Mutation
  • Nephrocalcinosis* / etiology
  • Nephrocalcinosis* / metabolism
  • Nephrocalcinosis* / physiopathology
  • Nephrolithiasis* / etiology
  • Nephrolithiasis* / metabolism
  • Nephrolithiasis* / physiopathology
  • Parathyroid Hormone / blood
  • Renal Insufficiency, Chronic / etiology
  • Renal Insufficiency, Chronic / prevention & control
  • Seasons
  • Sunlight / adverse effects*
  • Treatment Outcome
  • Vitamin D / analogs & derivatives*
  • Vitamin D / metabolism
  • Vitamin D / pharmacology
  • Vitamin D3 24-Hydroxylase / genetics*
  • Vitamin D3 24-Hydroxylase / metabolism


  • Bone Density Conservation Agents
  • Diphosphonates
  • Parathyroid Hormone
  • Vitamin D
  • 1,25-dihydroxyvitamin D
  • CYP24A1 protein, human
  • Vitamin D3 24-Hydroxylase
  • Calcium