WordNet
- childhood disease caused by deficiency of vitamin D and sunlight associated with impaired metabolism of calcium and phosphorus (同)rachitis
PrepTutorEJDIC
- くる病
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/01/13 14:09:31」(JST)
[Wiki en表示]
| X-linked hypophosphatemia |
| Classification and external resources |
| ICD-10 |
E83.3 |
| ICD-9 |
275.3 |
| OMIM |
307800 |
| DiseasesDB |
6513 |
| eMedicine |
ped/1128 article/922305
MeshName = |
| MeSH |
D053098 |
X-linked hypophosphatemia (XLH), also called X-linked dominant hypophosphatemic rickets, X-linked vitamin d-resistant rickets ,[1] is an X-linked dominant form of rickets (or osteomalacia) that differs from most cases of rickets in that ingestion of vitamin D is relatively ineffective. It can cause bone deformity including short stature and genu varum (bow leggedness). It is associated with a mutation in the PHEX gene sequence (Xp.22) and subsequent inactivity of the PHEX protein.[2] The prevalence of the disease is 1:20000.[3] The leg deformity can be treated with Ilizarov frames and CHAOS surgery.
Contents
- 1 Cause and Genetics
- 2 Treatment
- 3 See also
- 4 References
- 5 External links
Cause and Genetics
X-linked dominant inheritance works differently depending upon whether the mother (left image) or father (right image) is the carrier of a gene that causes a disease or disorder
XLH is associated with a mutation in the PHEX gene sequence, located on the human X chromosome at location Xp22.2-p22.1.[1][2][4] The PHEX protein regulates another protein called fibroblast growth factor 23 (produced from the FGF23 gene). Fibroblast growth factor 23 normally inhibits the kidneys' ability to reabsorb phosphate into the bloodstream. Gene mutations in PHEX prevent it from correctly regulating fibroblast growth factor 23. The resulting overactivity of this protein reduces phosphate reabsorption by the kidneys, leading to hypophosphatemia and the related features of hereditary hypophosphatemic rickets. Also, in the absence of PHEX enzymatic activity, osteopontin[5] — a mineralization-inhibiting secreted substrate protein found in the extracellular matrix of bone[6] — may accumulate in the bone to contribute to the osteomalacia as shown in the mouse homolog (Hyp) of XLH.[7] Biochemically, XLH is recognized by hypophosphatemia and inappropriately high level of calcitriol (1,25-(OH)2 vitamin D3). It also affects their equilibrium, only to the effect of their balance, which their knee/ankle joints are either farther outward or inward. A person affected by this disease usually cannot touch both knees and ankles together.
The disorder is inherited in an X-linked dominant manner.[1][2] This means the defective gene responsible for the disorder (PHEX) is located on the X chromosome, and only one copy of the defective gene is sufficient to cause the disorder when inherited from a parent who has the disorder. Males are normally hemizygous for the X chromosome, having only one copy. As a result, X-linked dominant disorders usually show higher expressivity in males than females.
As the X chromosome is one of the sex chromosomes (the other being the Y chromosome), X-linked inheritance is determined by the gender of the parent carrying a specific gene and can often seem complex. This is because, typically, females have two copies of the X-chromosome and males have only one copy. The difference between dominant and recessive inheritance patterns also plays a role in determining the chances of a child inheriting an X-linked disorder from their parentage.
Treatment
Oral phosphate,[8] calcitriol,[8] And, in the event of severe bowing, an Osteotomy may be performed to correct the leg shape.[citation needed]
See also
References
- ^ a b c Online 'Mendelian Inheritance in Man' (OMIM) 307800"HYPOPHOSPHATEMIC RICKETS, X-LINKED DOMINANT; XLHR". 23 May 2011.
- ^ a b c Saito, T.; Nishii, Y.; Yasuda, T.; Ito, N.; Suzuki, H.; Igarashi, T.; Fukumoto, S.; Fujita, T. (Oct 2009). "Familial hypophosphatemic rickets caused by a large deletion in PHEX gene". European Journal of Endocrinology 161 (4): 647–651. doi:10.1530/EJE-09-0261. PMID 19581284. edit
- ^ Carpenter TO (Apr 1997). "New perspectives on the biology and treatment of X-linked hypophosphatemic rickets". Pediatr. Clin. North Am. 44 (2): 443–466. doi:10.1016/S0031-3955(05)70485-5. PMID 9130929.
- ^ 300550"PHOSPHATE-REGULATING ENDOPEPTIDASE HOMOLOG, X-LINKED; PHEX". 18 April 2011.
- ^ Sodek, J; et al (2000). "Osteopontin". Critical Reviews in Oral Biology and Medicine 11 (3): 279–303. doi:10.1177/10454411000110030101. PMID 11021631.
- ^ McKee, MD; et al (2005). "Hierarchies of extracellular matrix and mineral organization in bone of the craniofacial complex and skeleton". Cells Tissues Organs 181 (3–4): 176–188. doi:10.1159/000091379. PMID 16612083.
- ^ Barros, NMT; et al (2013). "Proteolytic processing of osteopontin by PHEX and accumulation of osteopontin fragments in Hyp mouse bone, the murine model of X-linked hypophosphatemia". Journal of Bone and Mineral Research 28 (3): 688–699. doi:10.1002/jbmr.1766. PMID 22991293.
- ^ a b Imel, E. A.; DiMeglio, L. A.; Hui, S. L.; Carpenter, T. O.; Econs, M. J. (15 February 2010). "Treatment of X-Linked Hypophosphatemia with Calcitriol and Phosphate Increases Circulating Fibroblast Growth Factor 23 Concentrations". Journal of Clinical Endocrinology & Metabolism 95 (4): 1846–1850. doi:10.1210/jc.2009-1671. PMC 2853995. PMID 20157195.
External links
- 00754 at CHORUS
- Hypophosphatemic rickets; XLH; Hypophosphatemia, vitamin D-resistant rickets at NIH's Office of Rare Diseases
- The PHEXdb - a database of nucleotide variation in the PHEX gene
- The XLH Network Inc. - a worldwide patient support organization
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Inborn error of metal metabolism (E83, 275)
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| Transition metal |
| Fe |
| high: |
- Primary iron overload disorder: Hemochromatosis/HFE1
- Juvenile/HFE2
- HFE3
- African iron overload/HFE4
- Aceruloplasminemia
- Atransferrinemia
- Hemosiderosis
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| deficiency: |
|
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| Cu |
| high: |
- Copper toxicity
- Wilson's disease
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| deficiency: |
- Copper deficiency
- Menkes disease/Occipital horn syndrome
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|
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| Zn |
| high: |
|
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| deficiency: |
- Acrodermatitis enteropathica
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|
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| Electrolyte |
| Na+ and K+ |
- see Template:Water-electrolyte imbalance and acid-base imbalance
|
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| PO43− |
| high: |
|
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| deficiency: |
- Hypophosphatemia
- alkaline phosphatase
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| Mg2+ |
|
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| Ca2+ |
| high: |
- Hypercalcaemia
- Milk-alkali syndrome (Burnett's)
- Calcinosis (Calciphylaxis, Calcinosis cutis)
- Calcification (Metastatic calcification, Dystrophic calcification)
- Familial hypocalciuric hypercalcemia
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| deficiency: |
- Hypocalcaemia
- Osteomalacia
- Pseudohypoparathyroidism (Albright's hereditary osteodystrophy)
- Pseudopseudohypoparathyroidism
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| Description |
- Vitamins
- Cofactors
- Metal metabolism
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| Disease |
- Vitamins
- Metals
- Other
- Symptoms and signs
|
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| Treatment |
- Obesity drugs
- Vitamins
- Mineral supplements
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Sex linkage: X-linked disorders
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X-linked recessive
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| Immune |
- Chronic granulomatous disease (CYBB)
- Wiskott–Aldrich syndrome
- X-linked severe combined immunodeficiency
- X-linked agammaglobulinemia
- Hyper-IgM syndrome type 1
- IPEX
- X-linked lymphoproliferative disease
- Properdin deficiency
|
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| Hematologic |
- Haemophilia A
- Haemophilia B
- X-linked sideroblastic anemia
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| Endocrine |
- Androgen insensitivity syndrome/Spinal and bulbar muscular atrophy
- KAL1 Kallmann syndrome
- X-linked adrenal hypoplasia congenita
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| Metabolic |
- Amino acid: Ornithine transcarbamylase deficiency
- Oculocerebrorenal syndrome
- Dyslipidemia: Adrenoleukodystrophy
- Carbohydrate metabolism: Glucose-6-phosphate dehydrogenase deficiency
- Pyruvate dehydrogenase deficiency
- Danon disease/glycogen storage disease Type IIb
- Lipid storage disorder: Fabry's disease
- Mucopolysaccharidosis: Hunter syndrome
- Purine-pyrimidine metabolism: Lesch–Nyhan syndrome
- Mineral: Menkes disease/Occipital horn syndrome
|
|
| Nervous system |
- X-linked mental retardation: Coffin–Lowry syndrome
- MASA syndrome
- X-linked alpha thalassemia mental retardation syndrome
- Siderius X-linked mental retardation syndrome
- Eye disorders: Color blindness (red and green, but not blue)
- Ocular albinism (1)
- Norrie disease
- Choroideremia
- Other: Charcot–Marie–Tooth disease (CMTX2-3)
- Pelizaeus–Merzbacher disease
- SMAX2
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| Skin and related tissue |
- Dyskeratosis congenita
- Hypohidrotic ectodermal dysplasia (EDA)
- X-linked ichthyosis
- X-linked endothelial corneal dystrophy
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| Neuromuscular |
- Becker's muscular dystrophy/Duchenne
- Centronuclear myopathy (MTM1)
- Conradi–Hünermann syndrome
- Emery–Dreifuss muscular dystrophy 1
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| Urologic |
- Alport syndrome
- Dent's disease
- X-linked nephrogenic diabetes insipidus
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| Bone/tooth |
- AMELX Amelogenesis imperfecta
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| No primary system |
- Barth syndrome
- McLeod syndrome
- Smith–Fineman–Myers syndrome
- Simpson–Golabi–Behmel syndrome
- Mohr–Tranebjærg syndrome
- Nasodigitoacoustic syndrome
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X-linked dominant
|
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- X-linked hypophosphatemia
- Focal dermal hypoplasia
- Fragile X syndrome
- Aicardi syndrome
- Incontinentia pigmenti
- Rett syndrome
- CHILD syndrome
- Lujan–Fryns syndrome
- Orofaciodigital syndrome 1
- Craniofrontonasal dysplasia
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UpToDate Contents
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English Journal
- SPR4-peptide alters bone metabolism of normal and HYP mice.
- Zelenchuk LV1, Hedge AM1, Rowe PS2.
- Bone.Bone.2015 Mar;72:23-33. doi: 10.1016/j.bone.2014.11.011. Epub 2014 Nov 22.
- CONTEXT: ASARM-peptides are substrates and ligands for PHEX, the gene responsible for X-linked hypophosphatemic rickets (HYP). PHEX binds to the DMP1-ASARM-motif to form a trimeric-complex with α5β3-integrin on the osteocyte surface and this suppresses FGF23 expression. ASARM-peptide disruption of
- PMID 25460577
- Review of the dental implications of X-linked hypophosphataemic rickets (XLHR).
- Sabandal MM1, Robotta P, Bürklein S, Schäfer E.
- Clinical oral investigations.Clin Oral Investig.2015 Feb 13. [Epub ahead of print]
- OBJECTIVES: The aim of this article was to review the dental implications of X-linked hypophosphataemic rickets (XLHR) and to provide suggestions regarding the dental treatment of these patients.MATERIALS AND METHODS: The following search items "x-linked hypophosphataemia, hypophosphataemic rickets,
- PMID 25677243
Japanese Journal
- 低リン血症性くる病・骨軟化症 (特集 分子メカニズム解明がすすむ内分泌疾患)
- 内分泌・糖尿病・代謝内科 = Endocrinology, diabetology & metabolism 42(3), 179-184, 2016-03
- NAID 40020789790
- A de novo mosaic mutation of PHEX in a boy with hypophosphatemic rickets
- X連鎖性低リン血症性くる病におけるTmP/GFRの有用性
- 日本小児科学会雑誌 = The journal of the Japan Pediatric Society 119(4), 680-686, 2015-04
- NAID 40020468044
Related Links
- Hypophosphatemic rickets is a form of rickets that is characterized by low serum phosphate levels and resistance to treatment with ultraviolet radiation or vitamin D ingestion. The term rickets evolved from the old English ...
- Hereditary hypophosphatemic rickets can have several patterns of inheritance. When the condition results from mutations in the PHEX gene, it is inherited in an X-linked dominant pattern. The PHEX gene is located on the ...
Related Pictures
★リンクテーブル★
[★]
- 英
- hypophosphatemic rickets
- 関
- ビタミンD抵抗性くる病、X連鎖低リン血症性くる病、X染色体優性低リン血症性くる病、X連鎖性低リン酸血症
[★]
ビタミンD抵抗性くる病
- 関
- hypophosphatemic rickets、X-linked dominant hypophosphatemic rickets、X-linked hypophosphatemia、X-linked hypophosphatemic rickets
[★]
X連鎖性低リン酸血症
- 関
- hypophosphatemic rickets、vitamin D-resistant rickets、X-linked dominant hypophosphatemic rickets、X-linked hypophosphatemic rickets
[★]
X染色体優性低リン血症性くる病
- 関
- hypophosphatemic rickets、vitamin D-resistant rickets、X-linked hypophosphatemia、X-linked hypophosphatemic rickets
[★]
X連鎖低リン血症性くる病
- 関
- hypophosphatemic rickets、vitamin D-resistant rickets、X-linked dominant hypophosphatemic rickets、X-linked hypophosphatemia
[★]
- 関
- hypophosphataemia、hypophosphataemic、hypophosphatemia