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Renal phosphate wasting

MedGen UID:
335116
Concept ID:
C1845169
Finding
Synonyms: Decreased renal tubular phosphate reabsorption; Decreased renal tubular reabsorption of phosphate; Decreased tubular maximum for phosphate reabsorption per glomerular filtration rate (TmP/GFR)
 
HPO: HP:0000117

Definition

High urine phosphate in the presence of hypophosphatemia. [from HPO]

Conditions with this feature

Autosomal dominant hypophosphatemic rickets
MedGen UID:
83346
Concept ID:
C0342642
Disease or Syndrome
Autosomal dominant hypophosphatemic rickets (ADHR) is characterized by isolated renal phosphate wasting, hypophosphatemia, and inappropriately normal 1,25-dihydroxyvitamin D3 (calcitriol) levels. Patients frequently present with bone pain, rickets, and tooth abscesses. In contrast to X-linked dominant hypophosphatemic rickets (XLH; 307800), ADHR shows incomplete penetrance, variable age at onset (childhood to adult), and resolution of the phosphate-wasting defect in rare cases (Econs et al., 1997). See also hypophosphatemic bone disease (146350). Genetic Heterogeneity of Hypophosphatemic Rickets Other forms of hypophosphatemic rickets include autosomal recessive forms, i.e., ARHR1 (241520), caused by mutation in the DMP1 gene (600980) on chromosome 4q21, and ARHR2 (613312), caused by mutation in the ENPP1 gene (173335) on chromosome 6q23. An X-linked dominant form (XLHR; 307800) is caused by mutation in the PHEX gene (300550), and an X-linked recessive form (300554) is caused by mutation in the CLCN5 gene (300008). Clinical Variability of Hypophosphatemic Rickets Hypophosphatemic rickets can be caused by disorders of vitamin D metabolism or action (see VDDR1A, 264700). A form of hypophosphatemic rickets with hypercalciuria (HHRH; 241530) is caused by mutation in the SLC34A3 gene (609826), and there is evidence that a form of hypophosphatemic rickets with hyperparathyroidism (612089) may be caused by a translocation that results in an increase in alpha-klotho levels (KLOTHO; 604824).
Opsismodysplasia
MedGen UID:
140927
Concept ID:
C0432219
Disease or Syndrome
Opsismodysplasia (OPSMD) is a rare skeletal dysplasia involving delayed bone maturation. Clinical signs observed at birth include short limbs, small hands and feet, relative macrocephaly with a large anterior fontanel, and characteristic craniofacial abnormalities including a prominent brow, depressed nasal bridge, a small anteverted nose, and a relatively long philtrum. Death in utero or secondary to respiratory failure during the first few years of life has been reported, but there can be long-term survival. Typical radiographic findings include shortened long bones with delayed epiphyseal ossification, severe platyspondyly, metaphyseal cupping, and characteristic abnormalities of the metacarpals and phalanges (summary by Below et al., 2013 and Fradet and Fitzgerald, 2017).
Familial X-linked hypophosphatemic vitamin D refractory rickets
MedGen UID:
196551
Concept ID:
C0733682
Disease or Syndrome
The phenotypic spectrum of X-linked hypophosphatemia (XLH) ranges from isolated hypophosphatemia to severe lower-extremity bowing. XLH frequently manifests in the first two years of life when lower-extremity bowing becomes evident with the onset of weight bearing; however, it sometimes is not manifest until adulthood, as previously unevaluated short stature. In adults, enthesopathy (calcification of the tendons, ligaments, and joint capsules) associated with joint pain and impaired mobility may be the initial presenting complaint. Persons with XLH are prone to spontaneous dental abscesses; sensorineural hearing loss has also been reported.
Hypophosphatemic rickets, X-linked recessive
MedGen UID:
335115
Concept ID:
C1845168
Disease or Syndrome
X-linked recessive hypophosphatemic rickets is a form of X-linked hypercalciuric nephrolithiasis, which comprises a group of disorders characterized by proximal renal tubular reabsorptive failure, hypercalciuria, nephrocalcinosis, and renal insufficiency. These disorders have also been referred to as the 'Dent disease complex' (Scheinman, 1998; Gambaro et al., 2004). For a general discussion of Dent disease, see 300009.
Dent disease type 1
MedGen UID:
336322
Concept ID:
C1848336
Disease or Syndrome
Dent disease, an X-linked disorder of proximal renal tubular dysfunction, is characterized by low molecular weight (LMW) proteinuria, hypercalciuria, and at least one additional finding including nephrocalcinosis, nephrolithiasis, hematuria, hypophosphatemia, chronic kidney disease (CKD), and evidence of X-linked inheritance. Males younger than age ten years may manifest only LMW proteinuria and/or hypercalciuria, which are usually asymptomatic. Thirty to 80% of affected males develop end-stage renal disease (ESRD) between ages 30 and 50 years; in some instances ESRD does not develop until the sixth decade of life or later. The disease may also be accompanied by rickets or osteomalacia, growth restriction, and short stature. Disease severity can vary within the same family. Males with Dent disease 2 (caused by pathogenic variants in OCRL) may also have mild intellectual disability, cataracts, and/or elevated muscle enzymes. Due to random X-chromosome inactivation, some female carriers may manifest hypercalciuria and, rarely, renal calculi and moderate LMW proteinuria. Females rarely develop CKD.
Autosomal recessive hypophosphatemic bone disease
MedGen UID:
501133
Concept ID:
C1853271
Disease or Syndrome
Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare autosomal recessive disorder characterized by the presence of hypophosphatemia secondary to renal phosphate wasting, radiographic and/or histologic evidence of rickets, limb deformities, muscle weakness, and bone pain. HHRH is distinct from other forms of hypophosphatemic rickets in that affected individuals present with hypercalciuria due to increased serum 1,25-dihydroxyvitamin D levels and increased intestinal calcium absorption (summary by Bergwitz et al., 2006).
Hypophosphatemic nephrolithiasis/osteoporosis 2
MedGen UID:
394127
Concept ID:
C2676782
Disease or Syndrome
Hypophosphatemic nephrolithiasis/osteoporosis 1
MedGen UID:
436776
Concept ID:
C2676786
Disease or Syndrome
Hypophosphatemic rickets and hyperparathyroidism
MedGen UID:
383131
Concept ID:
C2677524
Disease or Syndrome
Fanconi renotubular syndrome 2
MedGen UID:
462002
Concept ID:
C3150652
Disease or Syndrome
Any Fanconi syndrome in which the cause of the disease is a mutation in the SLC34A1 gene.
Hypercalcemia, infantile, 2
MedGen UID:
934441
Concept ID:
C4310473
Disease or Syndrome
Infantile hypercalcemia is characterized by severe hypercalcemia with failure to thrive, vomiting, dehydration, and nephrocalcinosis (summary by Schlingmann et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of infantile hypercalcemia, see HCINF1 (143880).

Professional guidelines

PubMed

Baroncelli GI, Mora S
Front Endocrinol (Lausanne) 2021;12:688309. Epub 2021 Aug 6 doi: 10.3389/fendo.2021.688309. PMID: 34421819Free PMC Article
Laurent MR, De Schepper J, Trouet D, Godefroid N, Boros E, Heinrichs C, Bravenboer B, Velkeniers B, Lammens J, Harvengt P, Cavalier E, Kaux JF, Lombet J, De Waele K, Verroken C, van Hoeck K, Mortier GR, Levtchenko E, Vande Walle J
Front Endocrinol (Lausanne) 2021;12:641543. Epub 2021 Mar 19 doi: 10.3389/fendo.2021.641543. PMID: 33815294Free PMC Article
Haffner D, Emma F, Eastwood DM, Duplan MB, Bacchetta J, Schnabel D, Wicart P, Bockenhauer D, Santos F, Levtchenko E, Harvengt P, Kirchhoff M, Di Rocco F, Chaussain C, Brandi ML, Savendahl L, Briot K, Kamenicky P, Rejnmark L, Linglart A
Nat Rev Nephrol 2019 Jul;15(7):435-455. doi: 10.1038/s41581-019-0152-5. PMID: 31068690Free PMC Article

Recent clinical studies

Etiology

Leifheit-Nestler M, Vogt I, Haffner D, Richter B
Adv Exp Med Biol 2022;1362:107-134. doi: 10.1007/978-3-030-91623-7_11. PMID: 35288877
Laurent MR, De Schepper J, Trouet D, Godefroid N, Boros E, Heinrichs C, Bravenboer B, Velkeniers B, Lammens J, Harvengt P, Cavalier E, Kaux JF, Lombet J, De Waele K, Verroken C, van Hoeck K, Mortier GR, Levtchenko E, Vande Walle J
Front Endocrinol (Lausanne) 2021;12:641543. Epub 2021 Mar 19 doi: 10.3389/fendo.2021.641543. PMID: 33815294Free PMC Article
Cormier C
Joint Bone Spine 2019 Jul;86(4):459-466. Epub 2018 Oct 6 doi: 10.1016/j.jbspin.2018.10.001. PMID: 30300686
Insogna KL, Briot K, Imel EA, Kamenický P, Ruppe MD, Portale AA, Weber T, Pitukcheewanont P, Cheong HI, Jan de Beur S, Imanishi Y, Ito N, Lachmann RH, Tanaka H, Perwad F, Zhang L, Chen CY, Theodore-Oklota C, Mealiffe M, San Martin J, Carpenter TO; AXLES 1 Investigators
J Bone Miner Res 2018 Aug;33(8):1383-1393. Epub 2018 Jun 26 doi: 10.1002/jbmr.3475. PMID: 29947083
Carpenter TO, Imel EA, Holm IA, Jan de Beur SM, Insogna KL
J Bone Miner Res 2011 Jul;26(7):1381-8. Epub 2011 May 2 doi: 10.1002/jbmr.340. PMID: 21538511Free PMC Article

Diagnosis

Laurent MR, De Schepper J, Trouet D, Godefroid N, Boros E, Heinrichs C, Bravenboer B, Velkeniers B, Lammens J, Harvengt P, Cavalier E, Kaux JF, Lombet J, De Waele K, Verroken C, van Hoeck K, Mortier GR, Levtchenko E, Vande Walle J
Front Endocrinol (Lausanne) 2021;12:641543. Epub 2021 Mar 19 doi: 10.3389/fendo.2021.641543. PMID: 33815294Free PMC Article
Florenzano P, Hartley IR, Jimenez M, Roszko K, Gafni RI, Collins MT
Calcif Tissue Int 2021 Jan;108(1):128-142. Epub 2020 Jun 5 doi: 10.1007/s00223-020-00691-6. PMID: 32504138
Haffner D, Emma F, Eastwood DM, Duplan MB, Bacchetta J, Schnabel D, Wicart P, Bockenhauer D, Santos F, Levtchenko E, Harvengt P, Kirchhoff M, Di Rocco F, Chaussain C, Brandi ML, Savendahl L, Briot K, Kamenicky P, Rejnmark L, Linglart A
Nat Rev Nephrol 2019 Jul;15(7):435-455. doi: 10.1038/s41581-019-0152-5. PMID: 31068690Free PMC Article
Cormier C
Joint Bone Spine 2019 Jul;86(4):459-466. Epub 2018 Oct 6 doi: 10.1016/j.jbspin.2018.10.001. PMID: 30300686
Carpenter TO, Imel EA, Holm IA, Jan de Beur SM, Insogna KL
J Bone Miner Res 2011 Jul;26(7):1381-8. Epub 2011 May 2 doi: 10.1002/jbmr.340. PMID: 21538511Free PMC Article

Therapy

Baroncelli GI, Mora S
Front Endocrinol (Lausanne) 2021;12:688309. Epub 2021 Aug 6 doi: 10.3389/fendo.2021.688309. PMID: 34421819Free PMC Article
Laurent MR, De Schepper J, Trouet D, Godefroid N, Boros E, Heinrichs C, Bravenboer B, Velkeniers B, Lammens J, Harvengt P, Cavalier E, Kaux JF, Lombet J, De Waele K, Verroken C, van Hoeck K, Mortier GR, Levtchenko E, Vande Walle J
Front Endocrinol (Lausanne) 2021;12:641543. Epub 2021 Mar 19 doi: 10.3389/fendo.2021.641543. PMID: 33815294Free PMC Article
Florenzano P, Hartley IR, Jimenez M, Roszko K, Gafni RI, Collins MT
Calcif Tissue Int 2021 Jan;108(1):128-142. Epub 2020 Jun 5 doi: 10.1007/s00223-020-00691-6. PMID: 32504138
Haffner D, Emma F, Eastwood DM, Duplan MB, Bacchetta J, Schnabel D, Wicart P, Bockenhauer D, Santos F, Levtchenko E, Harvengt P, Kirchhoff M, Di Rocco F, Chaussain C, Brandi ML, Savendahl L, Briot K, Kamenicky P, Rejnmark L, Linglart A
Nat Rev Nephrol 2019 Jul;15(7):435-455. doi: 10.1038/s41581-019-0152-5. PMID: 31068690Free PMC Article
Felsenfeld AJ, Levine BS
Am J Kidney Dis 2012 Oct;60(4):655-61. Epub 2012 Aug 3 doi: 10.1053/j.ajkd.2012.03.024. PMID: 22863286

Prognosis

Şıklar Z, Turan S, Bereket A, Baş F, Güran T, Akberzade A, Abacı A, Demir K, Böber E, Özbek MN, Kara C, Poyrazoğlu Ş, Aydın M, Kardelen A, Tarım Ö, Eren E, Hatipoğlu N, Büyükinan M, Akyürek N, Çetinkaya S, Bayramoğlu E, Selver Eklioğlu B, Uçaktürk A, Abalı S, Gökşen D, Kor Y, Ünal E, Esen İ, Yıldırım R, Akın O, Çayır A, Dilek E, Kırel B, Anık A, Çatlı G, Berberoğlu M
J Clin Res Pediatr Endocrinol 2020 Jun 3;12(2):150-159. Epub 2019 Sep 13 doi: 10.4274/jcrpe.galenos.2019.2019.0098. PMID: 31514490Free PMC Article
Lambert AS, Zhukouskaya V, Rothenbuhler A, Linglart A
Joint Bone Spine 2019 Nov;86(6):731-738. Epub 2019 Jan 31 doi: 10.1016/j.jbspin.2019.01.012. PMID: 30711691
Cormier C
Joint Bone Spine 2019 Jul;86(4):459-466. Epub 2018 Oct 6 doi: 10.1016/j.jbspin.2018.10.001. PMID: 30300686
Hautmann AH, Hautmann MG, Kölbl O, Herr W, Fleck M
Curr Rheumatol Rep 2015 Jun;17(6):512. doi: 10.1007/s11926-015-0512-5. PMID: 25900190
Jan de Beur SM
JAMA 2005 Sep 14;294(10):1260-7. doi: 10.1001/jama.294.10.1260. PMID: 16160135

Clinical prediction guides

Verploegen MFA, Vargas-Poussou R, Walsh SB, Alpay H, Amouzegar A, Ariceta G, Atmis B, Bacchetta J, Bárány P, Baron S, Bayrakci US, Belge H, Besouw M, Blanchard A, Bökenkamp A, Boyer O, Burgmaier K, Calò LA, Decramer S, Devuyst O, van Dyck M, Ferraro PM, Fila M, Francisco T, Ghiggeri GM, Gondra L, Guarino S, Hooman N, Hoorn EJ, Houillier P, Kamperis K, Kari JA, Konrad M, Levtchenko E, Lucchetti L, Lugani F, Marzuillo P, Mohidin B, Neuhaus TJ, Osman A, Papizh S, Perelló M, Rookmaaker MB, Conti VS, Santos F, Sawaf G, Serdaroglu E, Szczepanska M, Taroni F, Topaloglu R, Trepiccione F, Vidal E, Wan ER, Weber L, Yildirim ZY, Yüksel S, Zlatanova G, Bockenhauer D, Emma F, Nijenhuis T
Nephrol Dial Transplant 2022 Nov 23;37(12):2474-2486. doi: 10.1093/ndt/gfac029. PMID: 35137195Free PMC Article
Lecoq AL, Chaumet-Riffaud P, Blanchard A, Dupeux M, Rothenbuhler A, Lambert B, Durand E, Boros E, Briot K, Silve C, Francou B, Piketty M, Chanson P, Brailly-Tabard S, Linglart A, Kamenický P
J Bone Miner Res 2020 Jul;35(7):1263-1273. Epub 2020 Mar 27 doi: 10.1002/jbmr.3992. PMID: 32101626
Uday S, Sakka S, Davies JH, Randell T, Arya V, Brain C, Tighe M, Allgrove J, Arundel P, Pryce R, Högler W, Shaw NJ
Clin Nutr 2019 Oct;38(5):2246-2250. Epub 2018 Sep 28 doi: 10.1016/j.clnu.2018.09.028. PMID: 30314926
Bergwitz C, Miyamoto KI
Pflugers Arch 2019 Jan;471(1):149-163. Epub 2018 Aug 14 doi: 10.1007/s00424-018-2184-2. PMID: 30109410
Baum M, Syal A, Quigley R, Seikaly M
Pediatr Nephrol 2006 Aug;21(8):1067-74. Epub 2006 May 24 doi: 10.1007/s00467-006-0126-2. PMID: 16721588

Recent systematic reviews

Christensen S, Tebben PJ, Sas D, Creo AL
Horm Res Paediatr 2021;94(9-10):374-389. Epub 2021 Oct 19 doi: 10.1159/000520299. PMID: 34666334
Seefried L, Smyth M, Keen R, Harvengt P
Osteoporos Int 2021 Jan;32(1):7-22. Epub 2020 Jul 24 doi: 10.1007/s00198-020-05548-0. PMID: 32710160Free PMC Article

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