title: Severe hypercalcemic crisis in an infant with idiopathic infantile hypercalcemia caused by mutation in CYP24A1 gene.
abstract: We report on a male infant presenting at 4 months of age with failure to thrive, dehydration, hypotonia, lethargy, and vomiting. Laboratory and imaging tests revealed severe hypercalcemia (5.8 mmol/l), suppressed parathyroid hormone (0.41 pmol/l), hypercalciuria (8.0 mmol/mmol creatinine), elevated 25-hydroxyvitamin D3 (over 600 nmol/l), and nephrocalcinosis. These symptoms are characteristic of idiopathic infantile hypercalcemia (IIH, MIM 143880). Conservative therapy (parenteral rehydration, diuretics, corticosteroids, bisphosphonates, and vitamin D prophylaxis withdrawal) was not able to improve the symptoms and laboratory values, and acute hemodiafiltration was necessary to normalize hypercalcemia. Clinical symptoms resolved rapidly after normalization of serum calcium levels. Molecular genetic testing revealed a homozygous mutation (R396W) in the CYP24A1 gene (MIM 126065) encoding 25-hydroxyvitamin D3 24-hydroxylase, which is the key enzyme responsible for 1,25-dihydroxyvitamin D3 degradation. The CYP24A1 gene mutation leads to the increased sensitivity of the patients to even prophylactic doses of vitamin D and to the development of severe symptomatic hypercalcemia in patients with IIH.
  
  
  CONCLUSIONS
  Our patient is only the thirteenth patient with IIH caused by mutation in the CYP24A1 gene and the first one needing acute hemodiafiltration for severe symptomatic hypercalcemic crisis. In all patients with suspected IIH the DNA analysis for CYP24A1 gene mutations should be performed regardless of the type of vitamin D supplementation and serum levels of vitamin D.
authors.affiliation: Department of Paediatrics, 2nd Faculty of Medicine, Charles University in Prague, Prague, Czech Republic. filip.fencl@gmail.com
authors.forename: Filip
authors.initials: F
authors.lastname: Fencl
authors.forename: Květa
authors.initials: K
authors.lastname: Bláhová
authors.forename: Karl Peter
authors.initials: KP
authors.lastname: Schlingmann
authors.forename: Martin
authors.initials: M
authors.lastname: Konrad
authors.forename: Tomáš
authors.initials: T
authors.lastname: Seeman
mesh_terms: D002112:Calcifediol / Q000235:genetics*; D002118:Calcium / Q000097:blood*; D003937:Diagnosis, Differential; D006801:Humans; D006934:Hypercalcemia / Q000175:diagnosis / Q000235:genetics*; D007223:Infant; D008297:Male; D009154:Mutation; D013250:Steroid Hydroxylases / Q000235:genetics*; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D002112:Calcifediol; D002118:Calcium