Vitamin D hydroxylation-deficient rickets, type 1a

Preferred Label : Vitamin D hydroxylation-deficient rickets, type 1a;

Symbol : VDDR1A;

CISMeF acronym : PDDR1A; VDDR1A; VDD1;

Type : Phenotype, molecular basis known;

Alternative titles and symbols : 1-alpha-hydroxylase deficiency; Pseudovitamin D-deficiency rickets, type ia; VDD1; Vitamin D dependency, type 1; PDDR1A; 1-alpha, 25-hydroxyvitamin d3 deficiency, selective; Pddr ia; Vitamin D-dependent rickets, type 1a; 25-hydroxycholecalciferol-1-hydroxylase deficiency;

Description : 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. - Other Forms of Hypophosphatemic Rickets For a discussion of other forms of hypophosphatemic rickets, see ADHR (193100).;

Inheritance : Autosomal recessive;

Molecular basis : Caused by mutations in the 25-hydroxyvitamin D3-1-alpha-hydroxylase gene (CYP27B1, 609506.0001).;

Laboratory abnormalities : Hypocalcemia; Hypophosphatemia; Normal serum 25-hydroxyvitamin D3; Increased serum alkaline phosphatase; Generalized aminoaciduria; Increased serum parathyroid hormone (PTH); Markedly decreased or absent serum 1,25-dihydroxyvitamin D3;

Prefixed ID : #264700;

Details

Origin ID

264700;

UMLS CUI

C0268689;

Automatic exact mappings (from CISMeF team)
- CYP27B1 wt Allele [NCIt concept]
Currated CISMeF NLP mapping
- Hypocalcemic vitamin D-dependent rickets [ORDO Disease]
- Vitamin D 1 Alpha-Hydroxylase Deficiency [NCIt concept]
- Vitamin D-dependent rickets, type 1 (disorder) [SNOMED CT concept]
- pseudovitamin D deficiency rickets [Disease (Nov.)]
- vitamin D Hydroxylation-Deficient rickets, type 1A [MeSH concept]
- vitamin D Hydroxylation-Deficient rickets, type 1A [MeSH Supplementary Concept]
DO Cross reference
- rickets [DO Concept]
Genes related to phenotype
- Cytochrome p450, subfamily xxviib, polypeptide 1 [OMIM gene]
HPO term(s)
- Abdominal wall muscle weakness [HPO term]
- Autosomal recessive inheritance [HPO term]
- Bone pain [HPO term]
- Bowing of the legs [HPO term]
- Bulging epiphyses [HPO term]
- Bulging of the costochondral junction [HPO term]
- Curvatures of the femur, tibia, fibula [HPO term]
- Deformed rib cage [HPO term]
- Delayed epiphyseal ossification [HPO term]
- Delayed eruption of teeth [HPO term]
- Difficulty standing [HPO term]
- Difficulty walking [HPO term]
- Elevated circulating alkaline phosphatase concentration [HPO term]
- Elevated circulating parathyroid hormone level [HPO term]
- Enamel hypoplasia [HPO term]
- Enlargement of the ankles [HPO term]
- Enlargement of the costochondral junction [HPO term]
- Enlargement of the wrists [HPO term]
- Failure to thrive [HPO term]
- Femoral bowing [HPO term]
- Fibular bowing [HPO term]
- Flat occiput [HPO term]
- Frayed, irregular metaphyses [HPO term]
- Frontal bossing [HPO term]
- Generalized aminoaciduria [HPO term]
- Generalized hypotonia [HPO term]
- Growth delay [HPO term]
- Hypocalcemic seizures [HPO term]
- Hypophosphatemia [HPO term]
- Hypotonia [HPO term]
- Irritability [HPO term]
- Metaphyseal irregularity [HPO term]
- Motor delay [HPO term]
- Posterior flattening of the skull [HPO term]
- Protuberant abdomen [HPO term]
- Protuberant abdomen due to muscle weakness [HPO term]
- Recurrent fractures [HPO term]
- Rickets [HPO term]
- Secondary hyperparathyroidism [HPO term]
- Sparse bone trabeculae [HPO term]
- Subperiosteal bone resorption [HPO term]
- Thin bony cortex [HPO term]
- Tibial bowing [HPO term]
- Widely patent fontanelles and sutures [HPO term]
ORDO concept(s)
- Hypocalcemic vitamin D-dependent rickets [ORDO Disease]
Semantic type(s)
- Disease or Syndrome [UMLS semantic type]
UMLS correspondences (same concept)
- Hypocalcemic vitamin D-dependent rickets [ORDO Disease]
- Vitamin D 1 Alpha-Hydroxylase Deficiency [NCIt concept]
- Vitamin D-dependent rickets, type 1 (disorder) [SNOMED CT concept]
- pseudovitamin D deficiency rickets [Disease (Nov.)]
- vitamin D Hydroxylation-Deficient rickets, type 1A [MeSH Supplementary Concept]
- vitamin D Hydroxylation-Deficient rickets, type 1A [MeSH concept]
- vitamin d-dependent rickets, type 1 [SNOMED Notion]

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