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Vitamin D hydroxylation-deficient rickets, type 1B(VDDR1B)

MedGen UID:
374020
Concept ID:
C1838657
Disease or Syndrome
Synonyms: PSEUDOVITAMIN D3 DEFICIENCY RICKETS DUE TO 25-HYDROXYLASE DEFICIENCY; VITAMIN D-DEPENDENT RICKETS, TYPE 1B
 
Gene (location): CYP2R1 (11p15.2)
 
Monarch Initiative: MONDO:0010810
OMIM®: 600081

Definition

Vitamin D hydroxylation-deficient rickets type 1B (VDDR1B) is caused by a defect in vitamin D 25-hydroxylation (Molin et al., 2017). The major function of vitamin D is to maintain calcium and phosphate levels in the normal range to support metabolic functions, neuromuscular transmission, and bone mineralization. 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 (summary by Liberman and Marx, 2001). Rickets can occur because of inadequate dietary intake or sun exposure or because of genetic disorders. Vitamin D3 (cholecalciferol) is taken in the diet or synthesized in the skin from 7-dehydrocholesterol by ultraviolet irradiation. For vitamin D to be active, it needs to be converted to its active form, 1,25-dihydroxyvitamin D3. Vitamin D is transported in the blood by the vitamin D binding protein (DBP; 139200) to the liver, where vitamin D 25-hydroxylase (CYP2R1; 608713) is the key enzyme for 25-hydroxylation. Vitamin D 25(OH)D3, the major circulating form of vitamin D, is then transported to the kidney, where 25(OH)D3 is hydroxylated at the position of carbon 1 of the A ring, resulting in the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) (summary by Christakos et al., 2010). [from OMIM]

Clinical features

From HPO
Bone pain
MedGen UID:
57489
Concept ID:
C0151825
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to bone.
Tibial bowing
MedGen UID:
332360
Concept ID:
C1837081
Finding
A bending or abnormal curvature of the tibia.
Enlargement of the wrists
MedGen UID:
325479
Concept ID:
C1838663
Finding
Enlargement of the ankles
MedGen UID:
333151
Concept ID:
C1838664
Finding
Fibular bowing
MedGen UID:
869374
Concept ID:
C4023801
Anatomical Abnormality
A bending or abnormal curvature of the fibula.
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
Recurrent fractures
MedGen UID:
42094
Concept ID:
C0016655
Injury or Poisoning
The repeated occurrence of bone fractures (implying an abnormally increased tendency for fracture).
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Rickets
MedGen UID:
48470
Concept ID:
C0035579
Disease or Syndrome
Rickets is divided into two major categories including calcipenic and phosphopenic. Hypophosphatemia is described as a common manifestation of both categories. Hypophosphatemic rickets is the most common type of rickets that is characterized by low levels of serum phosphate, resistance to ultraviolet radiation or vitamin D intake. There are several issues involved in hypophosphatemic rickets such as calcium, vitamin D, phosphorus deficiencies. Moreover, other disorder can be associated with its occurrence such as absorption defects due to pancreatic, intestinal, gastric, and renal disorders and hepatobiliary disease. Symptoms are usually seen in childhood and can be varied in severity. Severe forms may be linked to bowing of the legs, poor bone growth, and short stature as well as joint and bone pain. Hypophosphatemic rickets are associated with renal excretion of phosphate, hypophosphatemia, and mineral defects in bones. The familial type of the disease is the most common type of rickets.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
Difficulty standing
MedGen UID:
69136
Concept ID:
C0241237
Sign or Symptom
Sparse bone trabeculae
MedGen UID:
371538
Concept ID:
C1833324
Finding
Thin bony cortex
MedGen UID:
318844
Concept ID:
C1833325
Finding
Abnormal thinning of the cortical region of bones.
Bulging epiphyses
MedGen UID:
371540
Concept ID:
C1833329
Finding
A morphological abnormality of epiphyses whereby they are abnormally outwardly curving (protuberant).
Flat occiput
MedGen UID:
332439
Concept ID:
C1837402
Finding
Reduced convexity of the occiput (posterior part of skull).
Deformed rib cage
MedGen UID:
374021
Concept ID:
C1838659
Anatomical Abnormality
Malformation of the rib cage.
Metaphyseal irregularity
MedGen UID:
325478
Concept ID:
C1838662
Finding
Irregularity of the normally smooth surface of the metaphyses.
Bulging of the costochondral junction
MedGen UID:
338492
Concept ID:
C1848538
Finding
Abnormal outward curving (protuberance) of the junction of ribs and costal cartilage.
Widely patent fontanelles and sutures
MedGen UID:
336570
Concept ID:
C1849300
Finding
An abnormally increased width of the cranial fontanelles and sutures.
Enlargement of the costochondral junction
MedGen UID:
346535
Concept ID:
C1857180
Finding
Abnormally increased size of the costochondral junctions, which are located between the distal part of the ribs and the costal cartilages, which are bars of hyaline cartilage that connect the ribs to the sternum.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Femoral bowing
MedGen UID:
347888
Concept ID:
C1859461
Finding
Bowing (abnormal curvature) of the femur.
Delayed epiphyseal ossification
MedGen UID:
351324
Concept ID:
C1865200
Finding
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 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.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVVitamin D hydroxylation-deficient rickets, type 1B

Recent clinical studies

Diagnosis

Wiedemann A, Renard E, Molin A, Weryha G, Oussalah A, Guéant JL, Feillet F
Calcif Tissue Int 2020 Aug;107(2):191-194. Epub 2020 May 19 doi: 10.1007/s00223-020-00704-4. PMID: 32430692

Prognosis

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

Clinical prediction guides

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

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