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Vitamin D-dependent rickets, type 1A

MedGen UID:
968221
Concept ID:
CN283242
Disease or Syndrome
Synonyms: PDDR IA; PSEUDOVITAMIN D-DEFICIENCY RICKETS, TYPE IA; VITAMIN D HYDROXYLATION-DEFICIENT RICKETS, TYPE 1A
 
Gene (location): CYP27B1 (12q14.1)
 
Monarch Initiative: MONDO:0020723
OMIM®: 264700

Definition

Vitamin D3 (cholecalciferol), synthesized in the epidermis in response to UV radiation, and dietary vitamin D2 (ergocalciferol, synthesized in plants) are devoid of any biologic activity. Vitamin D hormonal activity is due primarily to the hydroxylated metabolite of vitamin D3, 1-alpha,25-dihydroxyvitamin D3 (calcitriol), the actions of which are mediated by the vitamin D receptor (VDR; 601769) (Koren, 2006; Liberman and Marx, 2001). In the liver, vitamin D 25-hydroxylase (CYP2R1; 608713) catalyzes the initial hydroxylation of vitamin D at carbon 25; in the kidney, 1-alpha-hydroxylase (CYP27B1; 609506) catalyzes the hydroxylation and metabolic activation of 25-hydroxyvitamin D3 into 1,25-dihydroxyvitamin D3. The active metabolite 1,25(OH)2D3 binds and activates the nuclear vitamin D receptor, with subsequent regulation of physiologic events such as calcium homeostasis and cellular differentiation and proliferation (Takeyama et al., 1997). Disorders of vitamin D metabolism or action lead to defective bone mineralization and clinical features including intestinal malabsorption of calcium, hypocalcemia, secondary hyperparathyroidism, increased renal clearance of phosphorus, and hypophosphatemia. The combination of hypocalcemia and hypophosphatemia causes impaired mineralization of bone that results in rickets and osteomalacia (Liberman and Marx, 2001). Genetic Heterogeneity of Vitamin D-Dependent Rickets Vitamin D-dependent rickets type 1A (VDDR1A) is due to an enzymatic defect in synthesis of the active form of vitamin D caused by mutation in the CYP27B1 gene. VDDR1B (600081) is a form of rickets due to mutation in the gene encoding a vitamin D 25-hydroxylase (CYP2R1; 608713), another enzyme necessary for the synthesis of active vitamin D. Vitamin D-dependent rickets type 2A (VDDR2A; 277440) is caused by end-organ unresponsiveness of active vitamin D due to mutation in the gene encoding the vitamin D receptor (VDR; 601769). VDDR2B (600785) is an unusual form of end-organ unresponsiveness to active vitamin D due to an abnormal protein (see HNRNPC, 164020) that interferes with the function of the VDR. VDDR3 (619073) is a dominant form of VDDR caused by accelerated inactivation of vitamin D metabolites due to mutation in the CYP3A4 gene (124010). Other Forms of Hypophosphatemic Rickets For a discussion of other forms of hypophosphatemic rickets, see ADHR (193100). [from OMIM]

Professional guidelines

PubMed

Méaux MN, Harambat J, Rothenbuhler A, Léger J, Kamenicky P, Soskin S, Boyer O, Boros E, D'Anella P, Mignot B, Gebhart M, Vic P, Richard N, Thivichon-Prince B, Francou B, Linglart A, Bacchetta J, Molin A
J Clin Endocrinol Metab 2023 Mar 10;108(4):812-826. doi: 10.1210/clinem/dgac639. PMID: 36321535
Dodamani MH, Sehemby M, Memon SS, Sarathi V, Lila AR, Chapla A, Bhandare VV, Patil VA, Shah NS, Thomas N, Kunwar A, Bandgar TR
J Pediatr Endocrinol Metab 2021 Dec 20;34(12):1505-1513. Epub 2021 Sep 8 doi: 10.1515/jpem-2021-0403. PMID: 34492747
Michałus I, Rusińska A
Clin Genet 2018 Jul;94(1):103-114. Epub 2018 Mar 25 doi: 10.1111/cge.13229. PMID: 29417983

Recent clinical studies

Etiology

Méaux MN, Harambat J, Rothenbuhler A, Léger J, Kamenicky P, Soskin S, Boyer O, Boros E, D'Anella P, Mignot B, Gebhart M, Vic P, Richard N, Thivichon-Prince B, Francou B, Linglart A, Bacchetta J, Molin A
J Clin Endocrinol Metab 2023 Mar 10;108(4):812-826. doi: 10.1210/clinem/dgac639. PMID: 36321535
Dodamani MH, Sehemby M, Memon SS, Sarathi V, Lila AR, Chapla A, Bhandare VV, Patil VA, Shah NS, Thomas N, Kunwar A, Bandgar TR
J Pediatr Endocrinol Metab 2021 Dec 20;34(12):1505-1513. Epub 2021 Sep 8 doi: 10.1515/jpem-2021-0403. PMID: 34492747
Ozden A, Doneray H
J Pediatr Endocrinol Metab 2021 Jun 25;34(6):781-789. Epub 2021 Apr 7 doi: 10.1515/jpem-2020-0691. PMID: 33823104
Gjørup H, Beck-Nielsen SS, Haubek D
Clin Oral Investig 2018 Mar;22(2):745-755. Epub 2017 Jun 12 doi: 10.1007/s00784-017-2149-4. PMID: 28608052
Acar S, Demir K, Shi Y
J Clin Res Pediatr Endocrinol 2017 Dec 30;9(Suppl 2):88-105. Epub 2017 Dec 27 doi: 10.4274/jcrpe.2017.S008. PMID: 29280738Free PMC Article

Diagnosis

Méaux MN, Harambat J, Rothenbuhler A, Léger J, Kamenicky P, Soskin S, Boyer O, Boros E, D'Anella P, Mignot B, Gebhart M, Vic P, Richard N, Thivichon-Prince B, Francou B, Linglart A, Bacchetta J, Molin A
J Clin Endocrinol Metab 2023 Mar 10;108(4):812-826. doi: 10.1210/clinem/dgac639. PMID: 36321535
Dodamani MH, Sehemby M, Memon SS, Sarathi V, Lila AR, Chapla A, Bhandare VV, Patil VA, Shah NS, Thomas N, Kunwar A, Bandgar TR
J Pediatr Endocrinol Metab 2021 Dec 20;34(12):1505-1513. Epub 2021 Sep 8 doi: 10.1515/jpem-2021-0403. PMID: 34492747
Ozden A, Doneray H
J Pediatr Endocrinol Metab 2021 Jun 25;34(6):781-789. Epub 2021 Apr 7 doi: 10.1515/jpem-2020-0691. PMID: 33823104
Dursun F, Özgürhan G, Kırmızıbekmez H, Keskin E, Hacıhamdioğlu B
J Clin Res Pediatr Endocrinol 2019 Feb 20;11(1):34-40. Epub 2018 Oct 4 doi: 10.4274/jcrpe.galenos.2018.2018.0121. PMID: 30282619Free PMC Article
Acar S, Demir K, Shi Y
J Clin Res Pediatr Endocrinol 2017 Dec 30;9(Suppl 2):88-105. Epub 2017 Dec 27 doi: 10.4274/jcrpe.2017.S008. PMID: 29280738Free PMC Article

Therapy

Aftab S, Khan SA, Malik MI, Imran A, Anjum MN, Saeed A, Qureshi AA, Cheema HA
J Pediatr Endocrinol Metab 2023 Feb 23;36(2):152-157. Epub 2022 Dec 19 doi: 10.1515/jpem-2022-0550. PMID: 36524979
Méaux MN, Harambat J, Rothenbuhler A, Léger J, Kamenicky P, Soskin S, Boyer O, Boros E, D'Anella P, Mignot B, Gebhart M, Vic P, Richard N, Thivichon-Prince B, Francou B, Linglart A, Bacchetta J, Molin A
J Clin Endocrinol Metab 2023 Mar 10;108(4):812-826. doi: 10.1210/clinem/dgac639. PMID: 36321535
Al Homyani DK, Alhemaiani SK
Front Endocrinol (Lausanne) 2022;13:862022. Epub 2022 May 18 doi: 10.3389/fendo.2022.862022. PMID: 35663328Free PMC Article
Ozden A, Doneray H
J Pediatr Endocrinol Metab 2021 Jun 25;34(6):781-789. Epub 2021 Apr 7 doi: 10.1515/jpem-2020-0691. PMID: 33823104
Özcabı B, Tahmiscioğlu Bucak F, Jaferova S, Oruç Ç, Adrovic A, Ceylaner S, Ercan O, Evliyaoğlu O
J Clin Res Pediatr Endocrinol 2016 Dec 1;8(4):484-489. Epub 2016 Jun 29 doi: 10.4274/jcrpe.3128. PMID: 27353739Free PMC Article

Prognosis

Dodamani MH, Sehemby M, Memon SS, Sarathi V, Lila AR, Chapla A, Bhandare VV, Patil VA, Shah NS, Thomas N, Kunwar A, Bandgar TR
J Pediatr Endocrinol Metab 2021 Dec 20;34(12):1505-1513. Epub 2021 Sep 8 doi: 10.1515/jpem-2021-0403. PMID: 34492747
Ozden A, Doneray H
J Pediatr Endocrinol Metab 2021 Jun 25;34(6):781-789. Epub 2021 Apr 7 doi: 10.1515/jpem-2020-0691. PMID: 33823104
Giannakopoulos A, Efthymiadou A, Chrysis D
Horm Res Paediatr 2017;87(1):58-63. Epub 2016 Jun 11 doi: 10.1159/000446774. PMID: 27287609
Hu WW, Ke YH, He JW, Fu WZ, Wang C, Zhang H, Yue H, Gu JM, Zhang ZL
J Pediatr Endocrinol Metab 2014 Mar;27(3-4):335-41. doi: 10.1515/jpem-2013-0183. PMID: 24197768

Clinical prediction guides

Méaux MN, Harambat J, Rothenbuhler A, Léger J, Kamenicky P, Soskin S, Boyer O, Boros E, D'Anella P, Mignot B, Gebhart M, Vic P, Richard N, Thivichon-Prince B, Francou B, Linglart A, Bacchetta J, Molin A
J Clin Endocrinol Metab 2023 Mar 10;108(4):812-826. doi: 10.1210/clinem/dgac639. PMID: 36321535
Giannakopoulos A, Efthymiadou A, Chrysis D
Horm Res Paediatr 2017;87(1):58-63. Epub 2016 Jun 11 doi: 10.1159/000446774. PMID: 27287609
Miyai K, Onishi T, Kashimada K, Hasegawa Y
Endocr J 2015;62(1):61-8. Epub 2014 Oct 4 doi: 10.1507/endocrj.EJ14-0085. PMID: 25284246
Hu WW, Ke YH, He JW, Fu WZ, Wang C, Zhang H, Yue H, Gu JM, Zhang ZL
J Pediatr Endocrinol Metab 2014 Mar;27(3-4):335-41. doi: 10.1515/jpem-2013-0183. PMID: 24197768

Recent systematic reviews

Dodamani MH, Sehemby M, Memon SS, Sarathi V, Lila AR, Chapla A, Bhandare VV, Patil VA, Shah NS, Thomas N, Kunwar A, Bandgar TR
J Pediatr Endocrinol Metab 2021 Dec 20;34(12):1505-1513. Epub 2021 Sep 8 doi: 10.1515/jpem-2021-0403. PMID: 34492747

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