X-linked hypophosphatemia

Last updated

X-linked hypophosphatemia
Other namesX-linked dominant hypophosphatemic rickets, or X-linked Vitamin D-resistant rickets, [1]
X-linked dominant.svg
This condition is inherited in an X-linked dominant manner.
Specialty Endocrinology, pediatrics   OOjs UI icon edit-ltr-progressive.svg
Complications osteomalacia (adults), rickets (children), fractures, enthesopathy, spinal stenosis, abnormal gait, short stature, tinnitus, hearing loss, dental complications, in rare exceptions Chiari malformation can occur.
CausesA genetic mutation of the PHEX gene results in elevated FGF23 hormone.
Medication phosphate, vitamin-D or burosumab

X-linked hypophosphatemia (XLH) is an X-linked dominant form of rickets (or osteomalacia) that differs from most cases of dietary deficiency rickets in that vitamin D supplementation does not cure it. 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] PHEX mutations lead to an elevated circulating (systemic) level of the hormone FGF23 which results in renal phosphate wasting, [3] and local elevations of the mineralization/calcification-inhibiting protein osteopontin in the extracellular matrix of bones and teeth. [4] [5] An inactivating mutation in the PHEX gene results in an increase in systemic circulating FGF23, and a decrease in the enzymatic activity of the PHEX enzyme which normally removes (degrades) mineralization-inhibiting osteopontin protein; in XLH, the decreased PHEX enzyme activity leads to an accumulation of inhibitory osteopontin locally in bones and teeth to block mineralization which, along with renal phosphate wasting, both cause osteomalacia and odontomalacia. [6] [7]

Contents

For both XLH and hypophosphatasia, inhibitor-enzyme pair relationships function to regulate mineralization in the extracellular matrix through a double-negative (inhibiting the inhibitors) activation effect in a manner described as the Stenciling Principle. [8] [9] Both these underlying mechanisms (renal phosphate wasting systemically, and mineralization inhibitor accumulation locally) contribute to the pathophysiology of XLH that leads to soft bones and teeth (hypomineralization, osteomalacia/odontomalacia). [10] [11] [12] The prevalence of the disease is 1 in 20,000. [13]

X-linked hypophosphatemia may be lumped in with autosomal dominant hypophosphatemic rickets under general terms such as hypophosphatemic rickets. Hypophosphatemic rickets are associated with at least nine other genetic mutations. [14] Clinical management of hypophosphatemic rickets may differ depending on the specific mutations associated with an individual case, but treatments are aimed at raising phosphate levels to promote normal bone formation. [15]

Symptoms and signs

The most common symptoms of XLH affect the bones and teeth, causing pain, abnormalities, and osteoarthritis. Symptoms and signs can vary between children and adults and can include:

Children

Adults

Genetics

XLH affects about 1:20,000 individuals and is the most common cause of inherited phosphate wasting. [26]

It is associated with a mutation in the PHEX gene sequence, located on the human X chromosome at location Xp22.2-p22.1. [1] [2] [29] 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 overactivity of FGF-23 reduces vitamin D 1α-hydroxylation and phosphate reabsorption by the kidneys, leading to hypophosphatemia and the related features of ricket. [30] Also in XLH, where PHEX enzymatic activity is absent or reduced, osteopontin [31] —a mineralization-inhibiting secreted substrate protein found in the extracellular matrix of bone [32] —accumulates in bone (and teeth) to contribute to the osteomalacia (and odontomalacia) as shown in the mouse homolog (Hyp) of XLH and in XLH patients. [33] [34] [35]

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.[ citation needed ]

As the X chromosome is one of the sex chromosomes (the other being the Y chromosome), X-linked inheritance is determined by the sex 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.[ citation needed ]

Diagnosis

The clinical laboratory evaluation of rickets begins with assessment of serum calcium, phosphate, and alkaline phosphatase levels. In hypophosphatemic rickets, calcium levels may be within or slightly below the reference range; alkaline phosphatase levels will be significantly above the reference range.Biochemically, XLH is recognized by hypophosphatemia. [36]

Carefully evaluate serum phosphate levels in the first year of life, because the concentration reference range for infants (5.0–7.5 mg/dL) is high compared with that for adults (2.7–4.5 mg/dL).[ citation needed ]

Serum parathyroid hormone levels are within the reference range or slightly elevated. calcitriol (1,25-(OH)2 vitamin D3) levels are low or within the lower reference range. Most importantly, urinary loss of phosphate is above the reference range.[ citation needed ]

The renal tubular reabsorption of phosphate (TRP) in X-linked hypophosphatemia is 60%; normal TRP exceeds 90% at the same reduced plasma phosphate concentration. The TRP is calculated with the following formula:[ citation needed ]

1 − [Phosphate Clearance (CPi) / Creatinine Clearance (Ccr)] × 100

Treatment

Conventional therapy consisted of medications including human growth hormone, calcitriol, and oral phosphate, [37] [38] and calcitriol; [37] [38] Unwanted effects of this therapy have included secondary hyperparathyroidism, nephrocalcinosis, kidney stones, and cardiovascular abnormalities.

In February 2018 the European Medicines Agency first licensed a monoclonal antibody directed against FGF23, the first drug targeting the underlying cause for this condition, [39] called burosumab. [40] It was then licensed by the US Food and Drug Administration in June 2018 [41]

The leg deformity can be treated with Ilizarov frames and CAOS. [42] In the event of severe bowing, an osteotomy can be performed to correct the leg shape. [42]

Society and culture

International XLH Alliance – an alliance of international patient groups for individuals affected by XLH and related disorders.

Jennyfer Marques Parinos is a Paralympic bronze medalist from Brazil who has XLH. She competes under a class 9 disability.

See also

Related Research Articles

<span class="mw-page-title-main">Rickets</span> Childhood bone disorder

Rickets is a condition that results in weak or soft bones in children, and is caused by either dietary deficiency or genetic causes. Symptoms include bowed legs, stunted growth, bone pain, large forehead, and trouble sleeping. Complications may include bone deformities, bone pseudofractures and fractures, muscle spasms, or an abnormally curved spine.

<span class="mw-page-title-main">Osteoblast</span> Cells secreting extracellular matrix

Osteoblasts are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts function in groups of connected cells. Individual cells cannot make bone. A group of organized osteoblasts together with the bone made by a unit of cells is usually called the osteon.

<span class="mw-page-title-main">Osteomalacia</span> Softening of bones due to impaired bone metabolism

Osteomalacia is a disease characterized by the softening of the bones caused by impaired bone metabolism primarily due to inadequate levels of available phosphate, calcium, and vitamin D, or because of resorption of calcium. The impairment of bone metabolism causes inadequate bone mineralization. Osteomalacia in children is known as rickets, and because of this, use of the term "osteomalacia" is often restricted to the milder, adult form of the disease. Signs and symptoms can include diffuse body pains, muscle weakness, and fragility of the bones. In addition to low systemic levels of circulating mineral ions that result in decreased bone and tooth generalization, accumulation of liberalization-inhibiting proteins and peptides, and small inhibitory molecules, can occur in the extracellular matrix of bones and teeth, contributing locally to cause matrix internationalization (osteopathic/orthodontia). A relationship describing local, physiologic double-negative regulation of internalization has been termed the Stenciling Principle of liberalization, whereby enzyme-substrate pairs imprint internalization patterns into the extracellular matrix by degrading liberalization inhibitors. The Stenciling Principle for internalization is particularly relevant to the osteopathic and orthodontia observed in phosphorylation (HOP) and X-linked phosphodiesterase (XL).

<span class="mw-page-title-main">Hypophosphatemia</span> Lack of phosphate in the blood

Hypophosphatemia is an electrolyte disorder in which there is a low level of phosphate in the blood. Symptoms may include weakness, trouble breathing, and loss of appetite. Complications may include seizures, coma, rhabdomyolysis, or softening of the bones.

<span class="mw-page-title-main">Osteocyte</span> Mature osteoblasts which helps in communication between cells and also in molecular synthesis

An osteocyte, an oblate shaped type of bone cell with dendritic processes, is the most commonly found cell in mature bone. It can live as long as the organism itself. The adult human body has about 42 billion of them. Osteocytes do not divide and have an average half life of 25 years. They are derived from osteoprogenitor cells, some of which differentiate into active osteoblasts. Osteoblasts/osteocytes develop in mesenchyme.

Renal osteodystrophy is currently defined as an alteration of bone morphology in patients with chronic kidney disease (CKD). It is one measure of the skeletal component of the systemic disorder of chronic kidney disease-mineral and bone disorder (CKD-MBD). The term "renal osteodystrophy" was coined in 1943, 60 years after an association was identified between bone disease and kidney failure.

<span class="mw-page-title-main">Hypophosphatasia</span> Medical condition

Hypophosphatasia (; also called deficiency of alkaline phosphatase, phosphoethanolaminuria, or Rathbun's syndrome; sometimes abbreviated HPP) is a rare, and sometimes fatal, inherited metabolic bone disease. Clinical symptoms are heterogeneous, ranging from the rapidly fatal, perinatal variant, with profound skeletal hypomineralization, respiratory compromise or vitamin B6 dependent seizures to a milder, progressive osteomalacia later in life. Tissue non-specific alkaline phosphatase (TNSALP) deficiency in osteoblasts and chondrocytes impairs bone mineralization, leading to rickets or osteomalacia. The pathognomonic finding is subnormal serum activity of the TNSALP enzyme, which is caused by one of 388 genetic mutations identified to date, in the gene encoding TNSALP. Genetic inheritance is autosomal recessive for the perinatal and infantile forms but either autosomal recessive or autosomal dominant in the milder forms.

<span class="mw-page-title-main">Osteopontin</span> Mammalian protein found in Homo sapiens

Osteopontin (OPN), also known as bone /sialoprotein I, early T-lymphocyte activation (ETA-1), secreted phosphoprotein 1 (SPP1), 2ar and Rickettsia resistance (Ric), is a protein that in humans is encoded by the SPP1 gene. The murine ortholog is Spp1. Osteopontin is a SIBLING (glycoprotein) that was first identified in 1986 in osteoblasts.

<span class="mw-page-title-main">Fibroblast growth factor 23</span> Protein-coding gene in the species Homo sapiens

Fibroblast growth factor 23 (FGF23) is a protein and member of the fibroblast growth factor (FGF) family which participates in the regulation of phosphate in plasma and vitamin D metabolism. In humans it is encoded by the FGF23 gene. FGF23 decreases reabsorption of phosphate in the kidney. Mutations in FGF23 can lead to its increased activity, resulting in autosomal dominant hypophosphatemic rickets.

<span class="mw-page-title-main">Autosomal dominant hypophosphatemic rickets</span> Medical condition

Autosomal dominant hypophosphatemic rickets (ADHR) is a rare hereditary disease in which excessive loss of phosphate in the urine leads to poorly formed bones (rickets), bone pain, and tooth abscesses. ADHR is caused by a mutation in the fibroblast growth factor 23 (FGF23). ADHR affects men and women equally; symptoms may become apparent at any point from childhood through early adulthood. Blood tests reveal low levels of phosphate (hypophosphatemia) and inappropriately normal levels of vitamin D. Occasionally, hypophosphatemia may improve over time as urine losses of phosphate partially correct.

Metabolic bone disease is an abnormality of bones caused by a broad spectrum of disorders. Most commonly these disorders are caused by deficiencies of minerals such as calcium, phosphorus, magnesium or vitamin D leading to dramatic clinical disorders that are commonly reversible once the underlying defect has been treated. These disorders are to be differentiated from a larger group of genetic bone disorders where there is a defect in a specific signaling system or cell type that causes the bone disorder. There may be overlap. For example, genetic or hereditary hypophosphatemia may cause the metabolic bone disorder osteomalacia. Although there is currently no treatment for the genetic condition, replacement of phosphate often corrects or improves the metabolic bone disorder. Metabolic bone disease in captive reptiles is also common, and is typically caused by calcium deficiency in a reptile's diet.

<span class="mw-page-title-main">PHEX</span> Protein-coding gene in the species Homo sapiens

Phosphate-regulating endopeptidase homolog X-linked also known as phosphate-regulating gene with homologies to endopeptidases on the X chromosome or metalloendopeptidase homolog PEX is an enzyme that in humans is encoded by the PHEX gene. This gene contains 18 exons and is located on the X chromosome.

<span class="mw-page-title-main">ALPL</span> Protein-coding gene in the species Homo sapiens

Alkaline phosphatase, tissue-nonspecific isozyme is an enzyme that in humans is encoded by the ALPL gene.

<span class="mw-page-title-main">DMP1</span> Protein-coding gene in the species Homo sapiens

Dentin matrix acidic phosphoprotein 1 is a protein that in humans is encoded by the DMP1 gene.

<span class="mw-page-title-main">MEPE</span> Protein-coding gene in the species Homo sapiens

Matrix extracellular phosphoglycoprotein is a protein that in humans is encoded by the MEPE gene. A conserved RGD motif is found in this protein, and this is potentially involved in integrin recognition.

<span class="mw-page-title-main">Sodium-dependent phosphate transport protein 2C</span> Protein-coding gene in the species Homo sapiens

Sodium-dependent phosphate transport protein 2C is a protein that in humans is encoded by the SLC34A3 gene.

Oncogenic osteomalacia, also known as oncogenic hypophosphatemic osteomalacia, is an uncommon disorder resulting in increased renal phosphate excretion, hypophosphatemia and osteomalacia. It may be caused by a phosphaturic mesenchymal tumor.

<span class="mw-page-title-main">FAM20C</span> Protein-coding gene in the species Homo sapiens

Family with sequence similarity 20, member C also known as FAM20C or DMP4 is a protein which in humans is encoded by the FAM20C gene. Fam20C, a Golgi localized protein kinase, is a serine kinase that phosphorylates both casein and other highly acidic proteins and members of the small integrin-binding ligand, the N-linked glycoproteins (SIBLING) family at the target motif SerXGlu.

Burosumab, sold under the brand name Crysvita, is a human monoclonal antibody medication approved 2018 for the treatment of X-linked hypophosphatemia and tumor-induced osteomalacia.

Phosphate diabetes is a rare, congenital, hereditary disorder associated with inadequate tubular reabsorption that affects the way the body processes and absorbs phosphate. Also named as X-linked dominant hypophosphatemic rickets (XLH), this disease is caused by a mutation in the X-linked PHEX gene, which encodes for a protein that regulates phosphate levels in the human body. phosphate is an essential mineral which plays a significant role in the formation and maintenance of bones and teeth, energy production and other important cellular processes. phosphate diabetes is a condition that falls under the category of tubulopathies, which refers to the pathologies of the renal tubules. The mutated PHEX gene causes pathological elevations in fibroblast growth factor 23 (FGF23), a hormone that regulates phosphate homeostasis by decreasing the reabsorption of phosphate in the kidneys.

References

  1. 1 2 3 Rasmussen SA, McKusick VA (June 23, 2023) [Originally published June 4, 1986], "HYPOPHOSPHATEMIC RICKETS, X-LINKED DOMINANT; XLHR", Online Mendelian Inheritance in Man, Johns Hopkins University 307800
  2. 1 2 3 Saito, T.; Nishii, Y.; Yasuda, T.; Ito, N.; Suzuki, H.; Igarashi, T.; Fukumoto, S.; Fujita, T. (October 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.
  3. ↑ Carpenter TO (June 8, 2022). "Primary Disorders of Phosphate Metabolism". In Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, et al. (eds.). Endotext. South Dartmouth, Massachusetts: MDText.com, Inc. PMID   25905395. National Library of Medicine Bookshelf ID NBK279172.
  4. ↑ Barros, NM; Hoac, B; Neves, RL; Addison, WN; Assis, DM; Murshed, M; Carmona, AK; McKee, MD (March 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): 688–99. doi: 10.1002/jbmr.1766 . PMID   22991293. S2CID   20840491.
  5. ↑ Boukpessi, T; Hoac, B; Coyac, BR; Leger, T; Garcia, C; Wicart, P; Whyte, MP; Glorieux, FH; Linglart, A; Chaussain, C; McKee, MD (February 2017). "Osteopontin and the dento-osseous pathobiology of X-linked hypophosphatemia". Bone. 95: 151–161. doi:10.1016/j.bone.2016.11.019. PMID   27884786.
  6. ↑ Boukpessi, T.; Hoac, B.; Coyac, B. R.; Leger, T.; Garcia, C.; Wicart, P.; Whyte, M. P.; Glorieux, F. H.; Linglart, A.; Chaussain, C.; McKee, M. D. (2017). "Osteopontin and the dento-osseous pathobiology of X-linked hypophosphatemia". Bone. 95: 151–161. doi:10.1016/j.bone.2016.11.019. PMID   27884786.
  7. ↑ Barros, N. M.; Hoac, B.; Neves, R. L.; Addison, W. N.; Assis, D. M.; Murshed, M.; Carmona, A. K.; McKee, M. D. (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. S2CID   20840491.
  8. ↑ Reznikov, N.; Hoac, B.; Buss, D. J.; Addison, W. N.; Barros NMT; McKee, M. D. (2020). "Biological stenciling of mineralization in the skeleton: Local enzymatic removal of inhibitors in the extracellular matrix". Bone. 138: 115447. doi:10.1016/j.bone.2020.115447. PMID   32454257. S2CID   218909350.
  9. ↑ McKee, M. D.; Buss, D. J.; Reznikov, N. (2022). "Mineral tessellation in bone and the Stenciling Principle for extracellular matrix mineralization". Journal of Structural Biology. 214 (1): 107823. doi:10.1016/j.jsb.2021.107823. PMID   34915130. S2CID   245187449.
  10. ↑ McKee, MD; Buss, DJ; Reznikov, N (December 13, 2021). "Mineral tessellation in bone and the stenciling principle for extracellular matrix mineralization". Journal of Structural Biology. 214 (1): 107823. doi:10.1016/j.jsb.2021.107823. PMID   34915130. S2CID   245187449.
  11. ↑ McKee, MD; Hoac, B; Addison, WN; Barros, NM; Millán, JL; Chaussain, C (October 2013). "Extracellular matrix mineralization in periodontal tissues: Noncollagenous matrix proteins, enzymes, and relationship to hypophosphatasia and X-linked hypophosphatemia". Periodontology 2000. 63 (1): 102–22. doi:10.1111/prd.12029. PMC   3766584 . PMID   23931057.
  12. ↑ Buss, DJ; Reznikov, N; McKee, MD (November 1, 2020). "Crossfibrillar mineral tessellation in normal and Hyp mouse bone as revealed by 3D FIB-SEM microscopy". Journal of Structural Biology. 212 (2): 107603. doi:10.1016/j.jsb.2020.107603. PMID   32805412. S2CID   221164596.
  13. ↑ Carpenter TO (April 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.
  14. ↑ Online Mendelian Inheritance in Man (OMIM): 193100
  15. ↑ "Hypophosphatemic rickets". Genetic and Rare Diseases Information Center. National Institutes of Health. Archived from the original on June 12, 2012. Retrieved October 10, 2012.
  16. 1 2 "Osteomalacia and Rickets". The Lecturio Medical Concept Library. Retrieved August 24, 2021.
  17. ↑ Silva, Sandra; Jeanty, Philippe (June 7, 1999). "Cloverleaf skull or kleeblattschadel". TheFetus.net. MacroMedia. Archived from the original on January 7, 2007. Retrieved February 3, 2007.
  18. 1 2 Luger, N. Mach, D. Sevcik, M. Mantyh, P. (2005). Bone cancer pain: From mechanism to model to therapy. Journal of Pain and Symptom Management. 29(5): 32-46.
  19. 1 2 "Fatigue". MedlinePlus. Retrieved April 30, 2020.
  20. 1 2 3 4 5 Linglart, A.; Biosse-Duplan, M.; Briot, K.; Chaussain, C.; Esterle, L.; Guillaume-Czitrom, S.; Kamenicky, P.; Nevoux, J.; Prié, D.; Rothenbuhler, A.; Wicart, P.; Harvengt, P. (2014). "Therapeutic management of hypophosphatemic rickets from infancy to adulthood". Endocrine Connections. 3 (1): R13–R30. doi:10.1530/EC-13-0103. PMC   3959730 . PMID   24550322.
  21. ↑ Buss, Daniel J.; Rechav, Katya; Reznikov, Natalie; McKee, Marc D. (September 2023). "Mineral tessellation in mouse enthesis fibrocartilage, Achilles tendon, and Hyp calcifying enthesopathy: A shared 3D mineralization pattern". Bone. 174: 116818. doi:10.1016/j.bone.2023.116818. ISSN   8756-3282. PMID   37295663. S2CID   259131061.
  22. ↑ "Overview of Bone Fractures". The Lecturio Medical Concept Library. Retrieved August 24, 2021.
  23. ↑ "Osteoarthritis". The Lecturio Medical Concept Library. Retrieved August 24, 2021.
  24. ↑ Skrinar, A.; Dvorak-Ewell, M.; Evins, A.; MacIca, C.; Linglart, A.; Imel, E. A.; Theodore-Oklota, C.; San Martin, J. (2019). "The Lifelong Impact of X-Linked Hypophosphatemia: Results From a Burden of Disease Survey". Journal of the Endocrine Society. 3 (7): 1321–1334. doi:10.1210/js.2018-00365. PMC   6595532 . PMID   31259293.
  25. ↑ Hawley, S.; Shaw, N. J.; Delmestri, A.; Prieto-Alhambra, D.; Cooper, C.; Pinedo-Villanueva, R.; Javaid, M. K. (2020). "Higher prevalence of non-skeletal comorbidity related to X-linked hypophosphataemia: a UK parallel cohort study using CPRD". Rheumatology. 60 (9): 4055–4062. doi:10.1093/rheumatology/keaa859. PMID   33331900.
  26. 1 2 Beck-Nielsen, Signe Sparre; Mughal, Zulf; Haffner, Dieter; Nilsson, Ola; Levtchenko, Elena; Ariceta, Gema; de Lucas Collantes, Carmen; Schnabel, Dirk; Jandhyala, Ravi; Mäkitie, Outi (February 26, 2019). "FGF23 and its role in X-linked hypophosphatemia-related morbidity". Orphanet Journal of Rare Diseases. 14 (1): 58. doi: 10.1186/s13023-019-1014-8 . ISSN   1750-1172. PMC   6390548 . PMID   30808384.
  27. ↑ Buss, Daniel J.; Reznikov, Natalie; McKee, Marc D. (November 2020). "Crossfibrillar mineral tessellation in normal and Hyp mouse bone as revealed by 3D FIB-SEM microscopy". Journal of Structural Biology. 212 (2): 107603. doi:10.1016/j.jsb.2020.107603. ISSN   1047-8477. PMID   32805412. S2CID   221164596.
  28. ↑ Buss, Daniel J.; Rechav, Katya; Reznikov, Natalie; McKee, Marc D. (September 2023). "Mineral tessellation in mouse enthesis fibrocartilage, Achilles tendon, and Hyp calcifying enthesopathy: A shared 3D mineralization pattern". Bone. 174: 116818. doi:10.1016/j.bone.2023.116818. ISSN   8756-3282. PMID   37295663. S2CID   259131061.
  29. ↑ Rasmussen SA, Kniffin CL (October 17, 2023) [Originally published July 28, 2005], "PHOSPHATE-REGULATING ENDOPEPTIDASE HOMOLOG, X-LINKED; PHEX", Online Mendelian Inheritance in Man, Johns Hopkins University 300550
  30. ↑ Perwad, Farzana; Zhang, Martin Y. H.; Tenenhouse, Harriet S.; Portale, Anthony A. (November 1, 2007). "Fibroblast growth factor 23 impairs phosphorus and vitamin D metabolism in vivo and suppresses 25-hydroxyvitamin D-1alpha-hydroxylase expression in vitro". American Journal of Physiology. Renal Physiology. 293 (5): F1577–1583. doi:10.1152/ajprenal.00463.2006. ISSN   1931-857X. PMID   17699549. S2CID   20559055.
  31. ↑ Sodek, J; et al. (2000). "Osteopontin". Critical Reviews in Oral Biology and Medicine. 11 (3): 279–303. doi: 10.1177/10454411000110030101 . PMID   11021631.
  32. ↑ 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. S2CID   40705942.
  33. ↑ McKee, MD; Hoac, B; Addison, WN; Barros, NM; Millán, JL; Chaussain, C (October 2013). "Extracellular matrix mineralization in periodontal tissues: Noncollagenous matrix proteins, enzymes, and relationship to hypophosphatasia and X-linked hypophosphatemia". Periodontology 2000. 63 (1): 102–22. doi:10.1111/prd.12029. PMC   3766584 . PMID   23931057.
  34. ↑ Boukpessi, T; Hoac, B; Coyac, BR; Leger, T; Garcia, C; Wicart, P; Whyte, MP; Glorieux, FH; Linglart, A; Chaussain, C; McKee, MD (November 21, 2016). "Osteopontin and the dento-osseous pathobiology of X-linked hypophosphatemia". Bone. 95: 151–161. doi:10.1016/j.bone.2016.11.019. PMID   27884786.
  35. ↑ 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.
  36. ↑ Haffner, Dieter; Emma, Francesco; Eastwood, Deborah M.; Duplan, Martin Biosse; Bacchetta, Justine; Schnabel, Dirk; Wicart, Philippe; Bockenhauer, Detlef; Santos, Fernando; Levtchenko, Elena; Harvengt, Pol; Kirchhoff, Martha; Di Rocco, Federico; Chaussain, Catherine; Brandi, Maria Louisa (July 2019). "Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia". Nature Reviews Nephrology. 15 (7): 435–455. doi:10.1038/s41581-019-0152-5. ISSN   1759-507X. PMC   7136170 . PMID   31068690.
  37. 1 2 Imel, E. A.; DiMeglio, L. A.; Hui, S. L.; Carpenter, T. O.; Econs, M. J. (February 15, 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.
  38. 1 2 Glorieux, F. H.; Marie, P. J.; Pettifor, J. M.; Delvin, E. E. (October 30, 1980). "Bone response to phosphate salts, ergocalciferol, and calcitriol in hypophosphatemic vitamin D-resistant rickets". The New England Journal of Medicine. 303 (18): 1023–1031. doi:10.1056/NEJM198010303031802. PMID   6252463.
  39. ↑ Carpenter, TO; Whyte MP; Imel EA; Boot AM; Högler W; Linglart A; Padidela R; Van't Hoff W; Mao M; Chen CY; Skrinar A; Kakkis E; San Martin J; Portale AA (May 24, 2018). "Burosumab Therapy in Children with X-Linked Hypophosphatemia". The New England Journal of Medicine (Submitted manuscript). 378 (21): 1987–1998. doi:10.1056/NEJMoa1714641. hdl: 1805/18603 . PMID   29791829. S2CID   44135503.
  40. ↑ "EMA authorisation details". September 17, 2018.
  41. ↑ "FDA press release".
  42. 1 2 "X-linked hypophosphatemia | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved October 21, 2018.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.