title: Maternal Hypercalcemia Due to Failure of 1,25-Dihydroxyvitamin-D3 Catabolism in a Patient With CYP24A1 Mutations.
abstract: BACKGROUND
  Calcium metabolism changes in pregnancy and lactation to meet fetal needs, with increases in 1,25-dihydroxyvitamin D [1,25-(OH)2D] during pregnancy playing an important role. However, these changes rarely cause maternal hypercalcemia. When maternal hypercalcemia occurs, further investigation is essential, and disorders of 1,25-(OH)2D catabolism should be carefully considered in the differential diagnosis.
  
  
  METHODS
  A patient with a childhood history of recurrent renal stone disease and hypercalciuria presented with recurrent hypercalcemia and elevated 1,25-(OH)2D levels during pregnancy. Laboratory tests in the fourth pregnancy showed suppressed PTH, elevated 1,25-(OH)2D, and high-normal 25-hydroxyvitamin D levels, suggesting disordered vitamin D metabolism. Analysis revealed low 24,25-dihydroxyvitamin D3 and high 25-hydroxyvitamin D3 levels, suggesting loss of function of CYP24A1 (25-hydroxyvitamin-D3-24-hydroxylase). Gene sequencing confirmed that she was a compound heterozygote with the E143del and R396W mutations in CYP24A1.
  
  
  CONCLUSIONS
  This case broadens presentations of CYP24A1 mutations and hypercalcemia in pregnancy. Furthermore, it illustrates that patients with CYP24A1 mutations can maintain normal calcium levels during the steady state but can develop hypercalcemia when challenged, such as in pregnancy when 1,25-(OH)2D levels are physiologically elevated.
authors.affiliation: Division of Endocrinology, Department of Medicine (A.D.S., E.C.H., D.S., I.B.K.), Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences (B.O., K.S.), and Division of Medical Genetics, Department of Medicine (R.N.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology and Metabolism (M.Kr., S.B.-P.), Medical University of Vienna, A-1090 Vienna, Austria; Department of Biomedical and Molecular Sciences (M.Ka., G.J.), Queen's University, Kingston, Ontario, Canada K7L 3N6; Endocrine Research Unit (D.D.B., Y.M., D.S.), San Francisco Department of Veterans Affairs Medical Center; San Francisco, California 94121; and Redwood Renal Associates (A.S.M.), Eureka, California 95501.
authors.forename: Arti D
authors.initials: AD
authors.lastname: Shah
authors.affiliation: Division of Endocrinology, Department of Medicine (A.D.S., E.C.H., D.S., I.B.K.), Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences (B.O., K.S.), and Division of Medical Genetics, Department of Medicine (R.N.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology and Metabolism (M.Kr., S.B.-P.), Medical University of Vienna, A-1090 Vienna, Austria; Department of Biomedical and Molecular Sciences (M.Ka., G.J.), Queen's University, Kingston, Ontario, Canada K7L 3N6; Endocrine Research Unit (D.D.B., Y.M., D.S.), San Francisco Department of Veterans Affairs Medical Center; San Francisco, California 94121; and Redwood Renal Associates (A.S.M.), Eureka, California 95501.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Hsiao
authors.affiliation: Division of Endocrinology, Department of Medicine (A.D.S., E.C.H., D.S., I.B.K.), Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences (B.O., K.S.), and Division of Medical Genetics, Department of Medicine (R.N.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology and Metabolism (M.Kr., S.B.-P.), Medical University of Vienna, A-1090 Vienna, Austria; Department of Biomedical and Molecular Sciences (M.Ka., G.J.), Queen's University, Kingston, Ontario, Canada K7L 3N6; Endocrine Research Unit (D.D.B., Y.M., D.S.), San Francisco Department of Veterans Affairs Medical Center; San Francisco, California 94121; and Redwood Renal Associates (A.S.M.), Eureka, California 95501.
authors.forename: Betsy
authors.initials: B
authors.lastname: O'Donnell
authors.affiliation: Division of Endocrinology, Department of Medicine (A.D.S., E.C.H., D.S., I.B.K.), Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences (B.O., K.S.), and Division of Medical Genetics, Department of Medicine (R.N.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology and Metabolism (M.Kr., S.B.-P.), Medical University of Vienna, A-1090 Vienna, Austria; Department of Biomedical and Molecular Sciences (M.Ka., G.J.), Queen's University, Kingston, Ontario, Canada K7L 3N6; Endocrine Research Unit (D.D.B., Y.M., D.S.), San Francisco Department of Veterans Affairs Medical Center; San Francisco, California 94121; and Redwood Renal Associates (A.S.M.), Eureka, California 95501.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Salmeen
authors.affiliation: Division of Endocrinology, Department of Medicine (A.D.S., E.C.H., D.S., I.B.K.), Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences (B.O., K.S.), and Division of Medical Genetics, Department of Medicine (R.N.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology and Metabolism (M.Kr., S.B.-P.), Medical University of Vienna, A-1090 Vienna, Austria; Department of Biomedical and Molecular Sciences (M.Ka., G.J.), Queen's University, Kingston, Ontario, Canada K7L 3N6; Endocrine Research Unit (D.D.B., Y.M., D.S.), San Francisco Department of Veterans Affairs Medical Center; San Francisco, California 94121; and Redwood Renal Associates (A.S.M.), Eureka, California 95501.
authors.forename: Robert
authors.initials: R
authors.lastname: Nussbaum
authors.affiliation: Division of Endocrinology, Department of Medicine (A.D.S., E.C.H., D.S., I.B.K.), Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences (B.O., K.S.), and Division of Medical Genetics, Department of Medicine (R.N.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology and Metabolism (M.Kr., S.B.-P.), Medical University of Vienna, A-1090 Vienna, Austria; Department of Biomedical and Molecular Sciences (M.Ka., G.J.), Queen's University, Kingston, Ontario, Canada K7L 3N6; Endocrine Research Unit (D.D.B., Y.M., D.S.), San Francisco Department of Veterans Affairs Medical Center; San Francisco, California 94121; and Redwood Renal Associates (A.S.M.), Eureka, California 95501.
authors.forename: Michael
authors.initials: M
authors.lastname: Krebs
authors.affiliation: Division of Endocrinology, Department of Medicine (A.D.S., E.C.H., D.S., I.B.K.), Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences (B.O., K.S.), and Division of Medical Genetics, Department of Medicine (R.N.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology and Metabolism (M.Kr., S.B.-P.), Medical University of Vienna, A-1090 Vienna, Austria; Department of Biomedical and Molecular Sciences (M.Ka., G.J.), Queen's University, Kingston, Ontario, Canada K7L 3N6; Endocrine Research Unit (D.D.B., Y.M., D.S.), San Francisco Department of Veterans Affairs Medical Center; San Francisco, California 94121; and Redwood Renal Associates (A.S.M.), Eureka, California 95501.
authors.forename: Sabina
authors.initials: S
authors.lastname: Baumgartner-Parzer
authors.affiliation: Division of Endocrinology, Department of Medicine (A.D.S., E.C.H., D.S., I.B.K.), Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences (B.O., K.S.), and Division of Medical Genetics, Department of Medicine (R.N.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology and Metabolism (M.Kr., S.B.-P.), Medical University of Vienna, A-1090 Vienna, Austria; Department of Biomedical and Molecular Sciences (M.Ka., G.J.), Queen's University, Kingston, Ontario, Canada K7L 3N6; Endocrine Research Unit (D.D.B., Y.M., D.S.), San Francisco Department of Veterans Affairs Medical Center; San Francisco, California 94121; and Redwood Renal Associates (A.S.M.), Eureka, California 95501.
authors.forename: Martin
authors.initials: M
authors.lastname: Kaufmann
authors.affiliation: Division of Endocrinology, Department of Medicine (A.D.S., E.C.H., D.S., I.B.K.), Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences (B.O., K.S.), and Division of Medical Genetics, Department of Medicine (R.N.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology and Metabolism (M.Kr., S.B.-P.), Medical University of Vienna, A-1090 Vienna, Austria; Department of Biomedical and Molecular Sciences (M.Ka., G.J.), Queen's University, Kingston, Ontario, Canada K7L 3N6; Endocrine Research Unit (D.D.B., Y.M., D.S.), San Francisco Department of Veterans Affairs Medical Center; San Francisco, California 94121; and Redwood Renal Associates (A.S.M.), Eureka, California 95501.
authors.forename: Glenville
authors.initials: G
authors.lastname: Jones
authors.affiliation: Division of Endocrinology, Department of Medicine (A.D.S., E.C.H., D.S., I.B.K.), Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences (B.O., K.S.), and Division of Medical Genetics, Department of Medicine (R.N.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology and Metabolism (M.Kr., S.B.-P.), Medical University of Vienna, A-1090 Vienna, Austria; Department of Biomedical and Molecular Sciences (M.Ka., G.J.), Queen's University, Kingston, Ontario, Canada K7L 3N6; Endocrine Research Unit (D.D.B., Y.M., D.S.), San Francisco Department of Veterans Affairs Medical Center; San Francisco, California 94121; and Redwood Renal Associates (A.S.M.), Eureka, California 95501.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Bikle
authors.affiliation: Division of Endocrinology, Department of Medicine (A.D.S., E.C.H., D.S., I.B.K.), Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences (B.O., K.S.), and Division of Medical Genetics, Department of Medicine (R.N.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology and Metabolism (M.Kr., S.B.-P.), Medical University of Vienna, A-1090 Vienna, Austria; Department of Biomedical and Molecular Sciences (M.Ka., G.J.), Queen's University, Kingston, Ontario, Canada K7L 3N6; Endocrine Research Unit (D.D.B., Y.M., D.S.), San Francisco Department of Veterans Affairs Medical Center; San Francisco, California 94121; and Redwood Renal Associates (A.S.M.), Eureka, California 95501.
authors.forename: YongMei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Division of Endocrinology, Department of Medicine (A.D.S., E.C.H., D.S., I.B.K.), Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences (B.O., K.S.), and Division of Medical Genetics, Department of Medicine (R.N.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology and Metabolism (M.Kr., S.B.-P.), Medical University of Vienna, A-1090 Vienna, Austria; Department of Biomedical and Molecular Sciences (M.Ka., G.J.), Queen's University, Kingston, Ontario, Canada K7L 3N6; Endocrine Research Unit (D.D.B., Y.M., D.S.), San Francisco Department of Veterans Affairs Medical Center; San Francisco, California 94121; and Redwood Renal Associates (A.S.M.), Eureka, California 95501.
authors.forename: Allen S
authors.initials: AS
authors.lastname: Mathew
authors.affiliation: Division of Endocrinology, Department of Medicine (A.D.S., E.C.H., D.S., I.B.K.), Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences (B.O., K.S.), and Division of Medical Genetics, Department of Medicine (R.N.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology and Metabolism (M.Kr., S.B.-P.), Medical University of Vienna, A-1090 Vienna, Austria; Department of Biomedical and Molecular Sciences (M.Ka., G.J.), Queen's University, Kingston, Ontario, Canada K7L 3N6; Endocrine Research Unit (D.D.B., Y.M., D.S.), San Francisco Department of Veterans Affairs Medical Center; San Francisco, California 94121; and Redwood Renal Associates (A.S.M.), Eureka, California 95501.
authors.forename: Dolores
authors.initials: D
authors.lastname: Shoback
authors.affiliation: Division of Endocrinology, Department of Medicine (A.D.S., E.C.H., D.S., I.B.K.), Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences (B.O., K.S.), and Division of Medical Genetics, Department of Medicine (R.N.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology and Metabolism (M.Kr., S.B.-P.), Medical University of Vienna, A-1090 Vienna, Austria; Department of Biomedical and Molecular Sciences (M.Ka., G.J.), Queen's University, Kingston, Ontario, Canada K7L 3N6; Endocrine Research Unit (D.D.B., Y.M., D.S.), San Francisco Department of Veterans Affairs Medical Center; San Francisco, California 94121; and Redwood Renal Associates (A.S.M.), Eureka, California 95501.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Block-Kurbisch
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000235:genetics* / Q000378:metabolism; D053858:Metabolic Networks and Pathways / Q000235:genetics; D009154:Mutation; D053040:Nephrolithiasis / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics* / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics*
chemical_list: D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase