Full Report

Format

Full Report
Summary (Text)
Summary (XML)

Send to:

Choose Destination

File
Clipboard
Collections

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): Gene(s) directly associated with this condition or phenotype.	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.

See: Feature record | Search on this feature

Growth delay

MedGen UID:: 99124
•Concept ID:: C0456070
•: Pathologic Function

A deficiency or slowing down of growth pre- and postnatally.

See: Feature record | Search on this feature

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.

See: Feature record | Search on this feature

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.

See: Feature record | Search on this feature

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.

See: Feature record | Search on this feature

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.

See: Feature record | Search on this feature

Bowing of the legs

MedGen UID:: 1807399
•Concept ID:: C5574706
•: Finding

A bending or abnormal curvature affecting a long bone of the leg.

See: Feature record | Search on this feature

Hypocalcemia

MedGen UID:: 5705
•Concept ID:: C0020598
•: Disease or Syndrome

An abnormally decreased calcium concentration in the blood.

See: Feature record | Search on this feature

Hypophosphatemia

MedGen UID:: 39327
•Concept ID:: C0085682
•: Disease or Syndrome

An abnormally decreased phosphate concentration in the blood.

See: Feature record | Search on this feature

Elevated circulating parathyroid hormone level

MedGen UID:: 167805
•Concept ID:: C0857973
•: Finding

An abnormal increased concentration of parathyroid hormone.

See: Feature record | Search on this feature

Elevated circulating alkaline phosphatase concentration

MedGen UID:: 727252
•Concept ID:: C1314665
•: Finding

Abnormally increased serum levels of alkaline phosphatase activity.

See: Feature record | Search on this feature

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.

See: Feature record | Search on this feature

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.

See: Feature record | Search on this feature

Show all Hide all

Abnormality of limbs
- Genu varum
Abnormality of metabolism/homeostasis
Abnormality of the musculoskeletal system
Abnormality of the nervous system
- Delayed ability to walk
Growth abnormality
- Growth delay

Professional guidelines

PubMed

Genotype-phenotype Description of Vitamin D-dependent Rickets 1A: CYP27B1 p.(Ala129Thr) Variant Induces a Milder Disease.

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

1 alpha-hydroxyvitamin D3 treatment of three patients with 1,25-dihydroxyvitamin D-receptor-defect rickets and alopecia.

Takeda E, Kuroda Y, Saijo T, Naito E, Kobashi H, Yokota I, Miyao M
Pediatrics 1987 Jul;80(1):97-101. PMID: 3037475

Hypercalcemic and hypocalcemic disorders: diagnosis and treatment.

Bell NH
Nephron 1979;23(2-3):147-51. doi: 10.1159/000181625. PMID: 440508

See all (3)

Recent clinical studies

Etiology

The pathophysiology of hypophosphatemia.

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

Genotype-phenotype Description of Vitamin D-dependent Rickets 1A: CYP27B1 p.(Ala129Thr) Variant Induces a Milder Disease.

Clinical and genetic analysis of two Chinese families with vitamin D-dependent rickets type IA and follow-up.

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: 33004071 Free PMC Article

Hereditary dentine disorders: dentinogenesis imperfecta and dentine dysplasia.

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: 19021896 Free PMC Article

1alpha-Hydroxylase and the action of vitamin D.

Hewison M, Zehnder D, Bland R, Stewart PM
J Mol Endocrinol 2000 Oct;25(2):141-8. doi: 10.1677/jme.0.0250141. PMID: 11013342

See all (18)

Diagnosis

The pathophysiology of hypophosphatemia.

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

Clinical spectrum and diagnostic challenges of vitamin D dependent rickets type 1A (VDDR1A) caused by CYP27B1 mutation in resource limited countries.

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

Genotype-phenotype Description of Vitamin D-dependent Rickets 1A: CYP27B1 p.(Ala129Thr) Variant Induces a Milder Disease.

A Case of Vitamin D-Dependent Rickets Type 1A with a Novel Mutation in the Uzbek Population.

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: 27353739 Free PMC Article

Hereditary dentine disorders: dentinogenesis imperfecta and dentine dysplasia.

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: 19021896 Free PMC Article

See all (26)

Therapy

Vitamin D-Dependent Rickets Type 3: A Case Report and Systematic Review.

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: 36656330 Free PMC Article

Clinical spectrum and diagnostic challenges of vitamin D dependent rickets type 1A (VDDR1A) caused by CYP27B1 mutation in resource limited countries.

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

Genotype-phenotype Description of Vitamin D-dependent Rickets 1A: CYP27B1 p.(Ala129Thr) Variant Induces a Milder Disease.

A Case of Vitamin D-Dependent Rickets Type 1A with a Novel Mutation in the Uzbek Population.

Genotype and Phenotype Characteristics in 22 Patients with Vitamin D-Dependent Rickets Type I.

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

See all (18)

Prognosis

Clinical presentation and molecular genetic analysis of a Sudanese family with a novel mutation in the CYP2R1 gene.

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

Clinical and genetic analysis of two Chinese families with vitamin D-dependent rickets type IA and follow-up.

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: 33004071 Free PMC Article

CYP2R1 mutations causing vitamin D-deficiency rickets.

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

Incidence and prevalence of nutritional and hereditary rickets in southern Denmark.

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

The combined use of intravenous and oral calcium for the treatment of vitamin D dependent rickets type II (VDDRII).

al-Aqeel A, Ozand P, Sobki S, Sewairi W, Marx S
Clin Endocrinol (Oxf) 1993 Aug;39(2):229-37. doi: 10.1111/j.1365-2265.1993.tb01779.x. PMID: 8396512

See all (11)

Clinical prediction guides

Genotype-phenotype Description of Vitamin D-dependent Rickets 1A: CYP27B1 p.(Ala129Thr) Variant Induces a Milder Disease.

CYP2R1 mutations causing vitamin D-deficiency rickets.

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

Genotype and Phenotype Characteristics in 22 Patients with Vitamin D-Dependent Rickets Type I.

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

Molecular genetics of vitamin D- dependent hereditary rickets.

Kato S, Yoshizazawa T, Kitanaka S, Murayama A, Takeyama K
Horm Res 2002;57(3-4):73-8. doi: 10.1159/000057955. PMID: 12006701

1alpha-Hydroxylase and the action of vitamin D.

Hewison M, Zehnder D, Bland R, Stewart PM
J Mol Endocrinol 2000 Oct;25(2):141-8. doi: 10.1677/jme.0.0250141. PMID: 11013342

See all (24)