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Vitamin D-dependent rickets, type 3(VDDR3)

MedGen UID:
1725534
Concept ID:
C5436733
Disease or Syndrome
Synonyms: VDDR3; VITAMIN D-DEPENDENT RICKETS, TYPE 3
 
Gene (location): CYP3A4 (7q22.1)
 
Monarch Initiative: MONDO:0033640
OMIM®: 619073

Definition

Vitamin D-dependent rickets-3 (VDDR3) is characterized by early-onset rickets, reduced serum levels of the vitamin D metabolites 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, and deficient responsiveness to the parent molecule as well as activated forms of vitamin D (Roizen et al., 2018). For discussion of genetic heterogeneity of vitamin D-dependent rickets, see 264700. [from OMIM]

Clinical features

From HPO
Genu varum
MedGen UID:
154257
Concept ID:
C0544755
Finding
A positional abnormality marked by outward bowing of the legs in which the knees stay wide apart when a person stands with the feet and ankles together.
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Delayed ability to walk
MedGen UID:
66034
Concept ID:
C0241726
Finding
A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.
Osteopenia
MedGen UID:
18222
Concept ID:
C0029453
Disease or Syndrome
Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5.
Metaphyseal cupping
MedGen UID:
323062
Concept ID:
C1837082
Finding
Metaphyseal cupping refers to an inward bulging of the metaphyseal profile giving the metaphysis a cup-like appearance.
Flared metaphysis
MedGen UID:
337976
Concept ID:
C1850135
Finding
The presence of a splayed (i.e.,flared) metaphyseal segment of one or more long bones.
Bowing of the legs
MedGen UID:
1807399
Concept ID:
C5574706
Finding
A bending or abnormal curvature affecting a long bone of the leg.
Hypocalcemia
MedGen UID:
5705
Concept ID:
C0020598
Disease or Syndrome
An abnormally decreased calcium concentration in the blood.
Hypophosphatemia
MedGen UID:
39327
Concept ID:
C0085682
Disease or Syndrome
An abnormally decreased phosphate concentration in the blood.
Elevated circulating parathyroid hormone level
MedGen UID:
167805
Concept ID:
C0857973
Finding
An abnormal increased concentration of parathyroid hormone.
Elevated circulating alkaline phosphatase concentration
MedGen UID:
727252
Concept ID:
C1314665
Finding
Abnormally increased serum levels of alkaline phosphatase activity.
Decreased circulating calcifediol concentration
MedGen UID:
868662
Concept ID:
C4023064
Finding
A reduced concentration of calcifediol in the blood. Calcifediol is also known as calcidiol, 25-hydroxycholecalciferol and 25-Hydroxyvitamin D3.
Low serum calcitriol
MedGen UID:
868663
Concept ID:
C4023065
Finding
A reduced concentration of calcitriol in the blood. Calcitriol is also known as 1,25-dihydroxycholecalciferol or 1,25-dihydroxyvitamin D3.

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
Takeda E, Kuroda Y, Saijo T, Naito E, Kobashi H, Yokota I, Miyao M
Pediatrics 1987 Jul;80(1):97-101. PMID: 3037475
Bell NH
Nephron 1979;23(2-3):147-51. doi: 10.1159/000181625. PMID: 440508

Recent clinical studies

Etiology

Ito N, Hidaka N, Kato H
Best Pract Res Clin Endocrinol Metab 2024 Mar;38(2):101851. Epub 2023 Nov 30 doi: 10.1016/j.beem.2023.101851. PMID: 38087658
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
Nishikawa M, Murose N, Mano H, Yasuda K, Isogai Y, Kittaka A, Takano M, Ikushiro S, Sakaki T
Sci Rep 2022 Jul 22;12(1):12517. doi: 10.1038/s41598-022-16819-7. PMID: 35869242Free PMC Article
Li Y, Yuan X, Chen R, Lin X, Shangguan H, Yang X, Zhang Y
Orphanet J Rare Dis 2020 Oct 1;15(1):273. doi: 10.1186/s13023-020-01558-7. PMID: 33004071Free PMC Article
Barron MJ, McDonnell ST, Mackie I, Dixon MJ
Orphanet J Rare Dis 2008 Nov 20;3:31. doi: 10.1186/1750-1172-3-31. PMID: 19021896Free PMC Article

Diagnosis

Ito N, Hidaka N, Kato H
Best Pract Res Clin Endocrinol Metab 2024 Mar;38(2):101851. Epub 2023 Nov 30 doi: 10.1016/j.beem.2023.101851. PMID: 38087658
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
Molin A, Wiedemann A, Demers N, Kaufmann M, Do Cao J, Mainard L, Dousset B, Journeau P, Abeguile G, Coudray N, Mittre H, Richard N, Weryha G, Sorlin A, Jones G, Kottler ML, Feillet F
J Bone Miner Res 2017 Sep;32(9):1893-1899. Epub 2017 Jul 13 doi: 10.1002/jbmr.3181. PMID: 28548312
Barron MJ, McDonnell ST, Mackie I, Dixon MJ
Orphanet J Rare Dis 2008 Nov 20;3:31. doi: 10.1186/1750-1172-3-31. PMID: 19021896Free PMC Article

Therapy

Mantoanelli L, de Almeida CM, Coelho MCA, Coutinho M, Levine MA, Collett-Solberg PF, Bordallo AP
Calcif Tissue Int 2023 Apr;112(4):512-517. Epub 2023 Jan 19 doi: 10.1007/s00223-022-01051-2. PMID: 36656330Free PMC Article
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
Molin A, Wiedemann A, Demers N, Kaufmann M, Do Cao J, Mainard L, Dousset B, Journeau P, Abeguile G, Coudray N, Mittre H, Richard N, Weryha G, Sorlin A, Jones G, Kottler ML, Feillet F
J Bone Miner Res 2017 Sep;32(9):1893-1899. Epub 2017 Jul 13 doi: 10.1002/jbmr.3181. PMID: 28548312
Tahir S, Demirbilek H, Ozbek MN, Baran RT, Tanriverdi S, Hussain K
Horm Res Paediatr 2016;85(5):309-17. Epub 2016 Mar 17 doi: 10.1159/000444483. PMID: 26982175

Prognosis

Abdalla AT, Koedam M, Drop SLS, Boot AM, Abdullah MA, van der Eerden BCJ
Gene 2022 Nov 30;844:146809. Epub 2022 Aug 13 doi: 10.1016/j.gene.2022.146809. PMID: 35973571
Li Y, Yuan X, Chen R, Lin X, Shangguan H, Yang X, Zhang Y
Orphanet J Rare Dis 2020 Oct 1;15(1):273. doi: 10.1186/s13023-020-01558-7. PMID: 33004071Free PMC Article
Thacher TD, Levine MA
J Steroid Biochem Mol Biol 2017 Oct;173:333-336. Epub 2016 Jul 27 doi: 10.1016/j.jsbmb.2016.07.014. PMID: 27473561
Beck-Nielsen SS, Brock-Jacobsen B, Gram J, Brixen K, Jensen TK
Eur J Endocrinol 2009 Mar;160(3):491-7. Epub 2008 Dec 18 doi: 10.1530/EJE-08-0818. PMID: 19095780
Gamblin GT, Liberman UA, Eil C, Downs RW Jr, DeGrange DA, Marx SJ
J Clin Invest 1985 Mar;75(3):954-60. doi: 10.1172/JCI111796. PMID: 3872316Free PMC Article

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
Nishikawa M, Murose N, Mano H, Yasuda K, Isogai Y, Kittaka A, Takano M, Ikushiro S, Sakaki T
Sci Rep 2022 Jul 22;12(1):12517. doi: 10.1038/s41598-022-16819-7. PMID: 35869242Free PMC Article
Thacher TD, Levine MA
J Steroid Biochem Mol Biol 2017 Oct;173:333-336. Epub 2016 Jul 27 doi: 10.1016/j.jsbmb.2016.07.014. PMID: 27473561
Tahir S, Demirbilek H, Ozbek MN, Baran RT, Tanriverdi S, Hussain K
Horm Res Paediatr 2016;85(5):309-17. Epub 2016 Mar 17 doi: 10.1159/000444483. PMID: 26982175
Kato S, Yoshizazawa T, Kitanaka S, Murayama A, Takeyama K
Horm Res 2002;57(3-4):73-8. doi: 10.1159/000057955. PMID: 12006701

Recent systematic reviews

Mantoanelli L, de Almeida CM, Coelho MCA, Coutinho M, Levine MA, Collett-Solberg PF, Bordallo AP
Calcif Tissue Int 2023 Apr;112(4):512-517. Epub 2023 Jan 19 doi: 10.1007/s00223-022-01051-2. PMID: 36656330Free PMC Article

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