| X-linked hypophosphatemia |
| Classification and external resources |
| ICD-10 |
E83.3 |
| ICD-9 |
275.3 |
| OMIM |
307800 |
| DiseasesDB |
6513 |
| eMedicine |
ped/1128 |
| MeSH |
D053098 |
X-linked hypophosphatemia (XLH), also called X-linked dominant hypophosphatemic rickets, X-linked vitamin d-resistant rickets or hypophosphatemic vitamin d-resistant rickets (HPDR),[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.
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Contents
- 1 Cause and Genetics
- 2 Difference in male to female
- 3 Treatment
- 4 See also
- 5 References
- 6 External links
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Cause and Genetics[edit]
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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
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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 mutation results in altered (or missing) activity of the PHEX protein, which inactivates hormone-like substances (phosphatonins) that promote phosphate excretion. The resulting excess excretion of phosphate impairs bone mineralization. Biochemically, XLH is recognized by hypophosphatemia and inappropriately low 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 unaffected 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.
Difference in male to female[edit]
An affected male males legs bow outwards (ankles touch, but not the knees), causing the identification of the disease to be at an later age than a females. Females legs bow inwards (knees touch, but not the ankles).
Treatment[edit]
Oral phosphate, calcitriol, and surgery if necessary.[citation needed]
See also[edit]
References[edit]
- ^ 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.
External links[edit]
- 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 |
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Fe
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high: Primary iron overload disorder: Hemochromatosis/HFE1 · Juvenile/HFE2 · HFE3 · African iron overload/HFE4 · Aceruloplasminemia · Atransferrinemia · Hemosiderosis
deficiency: Iron deficiency
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Cu
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high: Copper toxicity · Wilson's disease
deficiency: Copper deficiency · Menkes disease/Occipital horn syndrome
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Zn
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high: Zinc toxicity
deficiency: Acrodermatitis enteropathica
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| Electrolyte |
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Na+ and K+
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see Template:Water-electrolyte imbalance and acid-base imbalance
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PO43−
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high: Hyperphosphatemia
deficiency: Hypophosphatemia · alkaline phosphatase (Hypophosphatasia)
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Mg2+
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high: Hypermagnesemia
deficiency: Hypomagnesemia
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Ca2+
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high: Hypercalcaemia · Milk-alkali syndrome (Burnett's) · Calcinosis (Calciphylaxis, Calcinosis cutis) · Calcification (Metastatic calcification, Dystrophic calcification) · Familial hypocalciuric hypercalcemia
deficiency: Hypocalcaemia · Osteomalacia · Pseudohypoparathyroidism (Albright's hereditary osteodystrophy) · Pseudopseudohypoparathyroidism
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noco, nuvi, sysi/epon, met
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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/Kennedy disease
- 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
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| 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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