title: Kidney function and influence of sunlight exposure in patients with impaired 24-hydroxylation of vitamin D due to CYP24A1 mutations.
abstract: 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.
authors.affiliation: Néphrologie et Immunologie clinique, C.H.U Nantes, ITUN, Nantes, France. Electronic address: mlucile.figueres@gmail.com.
authors.forename: Marie-Lucile
authors.initials: ML
authors.lastname: Figueres
authors.affiliation: Endocrinologie et Diabète de l'Enfant, APHP Bicêtre Paris Sud, Le Kremlin-Bicètre, France; Inserm U986, Le Kremlin-Bicètre, France; Centre de référence des maladies rares du métabolisme du calcium et du phosphore, Bicêtre Paris Sud, Le Kremlin-Bicètre, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Linglart
authors.affiliation: Service d'Exploration Fonctionnelle et Centre de Recherche Croissance et Signalisation, Hôpital Necker Enfant Malade, Université Paris 5 Descartes, Paris, France.
authors.forename: Frank
authors.initials: F
authors.lastname: Bienaime
authors.affiliation: Néphrologie pédiatrique, C.H.U Nantes, Nantes, France.
authors.forename: Emma
authors.initials: E
authors.lastname: Allain-Launay
authors.affiliation: Néphrologie pédiatrique, C.H.U Nantes, Nantes, France; INSERM U643, Nantes, France.
authors.forename: Gwenaelle
authors.initials: G
authors.lastname: Roussey-Kessler
authors.affiliation: Néphrologie pédiatrique, C.H.U Rennes, Rennes, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Ryckewaert
authors.affiliation: Génétique médicale, C.H.U Caen, Caen, France.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Kottler
authors.affiliation: Néphrologie et Immunologie clinique, C.H.U Nantes, ITUN, Nantes, France.
authors.forename: Maryvonne
authors.initials: M
authors.lastname: Hourmant
mesh_terms: D050071:Bone Density Conservation Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004164:Diphosphonates / Q000494:pharmacology*; D005260:Female; D005440:Fluid Therapy / Q000379:methods*; D006801:Humans; D006934:Hypercalcemia / Q000235:genetics / Q000503:physiopathology; D053565:Hypercalciuria / Q000235:genetics / Q000503:physiopathology; D007223:Infant; D007677:Kidney Function Tests / Q000379:methods; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods; D009154:Mutation; D009397:Nephrocalcinosis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D053040:Nephrolithiasis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D010281:Parathyroid Hormone / Q000097:blood; D051436:Renal Insufficiency, Chronic / Q000209:etiology / Q000517:prevention & control; D012621:Seasons; D013472:Sunlight / Q000009:adverse effects*; D016896:Treatment Outcome; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics* / Q000378:metabolism
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D010281:Parathyroid Hormone; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D002118:Calcium
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