Hereditary Rickets: A Quick Guide for the Pediatrician

Abdulmajeed      AlSubaihin; Jennifer      Harrington
doi:10.2174/1573396319666221205123402
Abstract

With the increased discovery of genes implicated in vitamin D metabolism and the regulation of calcium and phosphate homeostasis, a growing number of genetic forms of rickets are now recognized. These are categorized into calciopenic and phosphopenic rickets. Calciopenic forms of hereditary rickets are caused by genetic mutations that alter the enzymatic activity in the vitamin D activation pathway or impair the vitamin D receptor action. Hereditary forms of phosphopenic rickets, on the other hand, are caused by genetic mutations that lead to increased expression of FGF23 hormone or that impair the absorptive capacity of phosphate at the proximal renal tubule. Due to the clinical overlap between acquired and genetic forms of rickets, identifying children with hereditary rickets can be challenging. A clear understanding of the molecular basis of hereditary forms of rickets and their associated biochemical patterns allow the health care provider to assign the correct diagnosis, avoid non-effective interventions and shorten the duration of the diagnostic journey in these children. In this mini-review, known forms of hereditary rickets listed on the Online Mendelian Inheritance in Man database are discussed. Further, a clinical approach to identify and diagnose children with hereditary forms of rickets is suggested.
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Graphical Abstract

[1]
Cone TE Jr. A rachitic infant painted by Burgkmair 136 years before Dr. Whistler described rickets. Clin Pediatr  1980; 19(3): 194.
 [http://dx.doi.org/10.1177/000992288001900305] [PMID: 6987020]

[2]
Clarke E. Whistler and Glisson on rickets. Bull Hist Med  1962; 36: 45-61.
 [PMID: 13879755]

[3]
Dunn PM. Francis Glisson (1597-1677) and the “discovery” of rickets. Arch Dis Child Fetal Neonatal Ed  1998; 78(2): F154-5.
 [http://dx.doi.org/10.1136/fn.78.2.F154] [PMID: 9577290]

[4]
Friedman A. A brief history of rickets. Pediatr Nephrol  2020; 35(10): 1835-41.
 [http://dx.doi.org/10.1007/s00467-019-04366-9] [PMID: 31654223]

[5]
Creo AL, Thacher TD, Pettifor JM, Strand MA, Fischer PR. Nutritional rickets around the world: An update. Paediatr Int Child Health  2017; 37(2): 84-98.
 [http://dx.doi.org/10.1080/20469047.2016.1248170] [PMID: 27922335]

[6]
Beck-Nielsen SS, Brock-Jacobsen B, Gram J, Brixen K, Jensen TK. Incidence and prevalence of nutritional and hereditary rickets in southern Denmark. Eur J Endocrinol  2009; 160(3): 491-7.
 [http://dx.doi.org/10.1530/EJE-08-0818] [PMID: 19095780]

[7]
Wheeler BJ, Dickson NP, Houghton LA, Ward LM, Taylor BJ. Incidence and characteristics of vitamin D deficiency rickets in New Zea-land children: a New Zealand Paediatric Surveillance Unit study. Aust N Z J Public Health  2015; 39(4): 380-3.
 [http://dx.doi.org/10.1111/1753-6405.12390] [PMID: 26122859]

[8]
Munns CF, Simm PJ, Rodda CP, et al. Incidence of vitamin D deficiency rickets among Australian children: An Australian Paediatric Sur-veillance Unit study. Med J Aust  2012; 196(7): 466-8.
 [http://dx.doi.org/10.5694/mja11.10662] [PMID: 22509879]

[9]
Julies P, Lynn RM, Pall K, et al. Nutritional rickets under 16 years: UK surveillance results. Arch Dis Child  2020; 105(6): 587-92.
 [http://dx.doi.org/10.1136/archdischild-2019-317934] [PMID: 31949032]

[10]
Kubota T, Nakayama H, Kitaoka T, et al. Incidence rate and characteristics of symptomatic vitamin D deficiency in children: A nationwide survey in Japan. Endocr J  2018; 65(6): 593-9.
 [http://dx.doi.org/10.1507/endocrj.EJ18-0008] [PMID: 29526992]

[11]
Ward LM, Gaboury I, Ladhani M, Zlotkin S. Vitamin D-deficiency rickets among children in Canada. CMAJ  2007; 177(2): 161-6.
 [http://dx.doi.org/10.1503/cmaj.061377] [PMID: 17600035]

[12]
Meyer HE, Skram K, Berge IA, Madar AA, Bjørndalen HJ. Nutritional rickets in Norway: A nationwide register-based cohort study. BMJ Open  2017; 7(5): e015289.
 [http://dx.doi.org/10.1136/bmjopen-2016-015289] [PMID: 28554929]

[13]
 An online catalog of human genes and genetic disorder: Available from: www.omim.org (Accessed on: Jan 1, 2022).

[14]
Bikle DD. Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol  2014; 21(3): 319-29.
 [http://dx.doi.org/10.1016/j.chembiol.2013.12.016] [PMID: 24529992]

[15]
Cheng JB, Levine MA, Bell NH, Mangelsdorf DJ, Russell DW. Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase. Proc Natl Acad Sci USA  2004; 101(20): 7711-5.
 [http://dx.doi.org/10.1073/pnas.0402490101] [PMID: 15128933]

[16]
Al Mutair AN, Nasrat GH, Russell DW. Mutation of the CYP2R1 vitamin D 25-hydroxylase in a Saudi Arabian family with severe vitamin D deficiency. J Clin Endocrinol Metab  2012; 97(10): E2022-5.
 [http://dx.doi.org/10.1210/jc.2012-1340] [PMID: 22855339]

[17]
Molin A, Wiedemann A, Demers N, et al. Vitamin D-dependent rickets type 1B (25-Hydroxylase Deficiency): A rare condition or a misdi-agnosed condition? J Bone Miner Res  2017; 32(9): 1893-9.
 [http://dx.doi.org/10.1002/jbmr.3181] [PMID: 28548312]

[18]
Thacher TD, Fischer PR, Singh RJ, Roizen J, Levine MA. CYP2R1 Mutations impair generation of 25-hydroxyvitamin D and cause an atypical form of vitamin D deficiency. J Clin Endocrinol Metab  2015; 100(7): E1005-13.
 [http://dx.doi.org/10.1210/jc.2015-1746] [PMID: 25942481]

[19]
Ozden A, Doneray H, Turkyilmaz A. Two novel CYP2R1 mutations in a family with vitamin D-dependent rickets type 1b. Endocrine  2021; 72(3): 852-64.
 [http://dx.doi.org/10.1007/s12020-021-02670-9] [PMID: 33715104]

[20]
Thacher TD, Levine MA. CYP2R1 mutations causing vitamin D-deficiency rickets. J Steroid Biochem Mol Biol  2017; 173: 333-6.
 [http://dx.doi.org/10.1016/j.jsbmb.2016.07.014] [PMID: 27473561]

[21]
Bakhamis S, Imtiaz F, Ramzan K, et al. 25-Hydroxylase vitamin D deficiency in 27 Saudi Arabian subjects: A clinical and molecular re-port on CYP2R1 mutations. Endocr Connect  2021; 10(7): 767-75.
 [http://dx.doi.org/10.1530/EC-21-0102] [PMID: 34137732]

[22]
Fu GK, Lin D, Zhang MY, et al. Cloning of human 25-hydroxyvitamin D-1 alpha-hydroxylase and mutations causing vitamin D-dependent rickets type 1. Mol Endocrinol  1997; 11(13): 1961-70.
 [PMID: 9415400]

[23]
Kitanaka S, Takeyama K, Murayama A, et al. Inactivating mutations in the 25-hydroxyvitamin D3 1alpha-hydroxylase gene in patients with pseudovitamin D-deficiency rickets. N Engl J Med  1998; 338(10): 653-62.
 [http://dx.doi.org/10.1056/NEJM199803053381004] [PMID: 9486994]

[24]
Koek WNH, Zillikens MC, van der Eerden BCJ, van Leeuwen JPTM. Novel compound heterozygous mutations in the CYP27B1 gene lead to pseudovitamin D-deficient rickets. Calcif Tissue Int  2016; 99(3): 326-31.
 [http://dx.doi.org/10.1007/s00223-016-0165-z] [PMID: 27364341]

[25]
Edouard T, Alos N, Chabot G, Roughley P, Glorieux FH, Rauch F. Short- and long-term outcome of patients with pseudo-vitamin D defi-ciency rickets treated with calcitriol. J Clin Endocrinol Metab  2011; 96(1): 82-9.
 [http://dx.doi.org/10.1210/jc.2010-1340] [PMID: 20926527]

[26]
Demir K, Kattan WE, Zou M, et al. Novel CYP27B1 gene mutations in patients with vitamin D-dependent rickets type 1A. PLoS One  2015; 10(7): e0131376.
 [http://dx.doi.org/10.1371/journal.pone.0131376] [PMID: 26132292]

[27]
Tahir S, Demirbilek H, Ozbek MN, Baran RT, Tanriverdi S, Hussain K. Genotype and phenotype characteristics in 22 patients with vita-min D-dependent rickets type I. Horm Res Paediatr  2016; 85(5): 309-17.
 [http://dx.doi.org/10.1159/000444483] [PMID: 26982175]

[28]
Dursun F, Özgürhan G, Kırmızıbekmez H, Keskin E, Hacıhamdioğlu B. Genetic and clinical characteristics of patients with vitamin D de-pendent rickets type 1A. J Clin Res Pediatr Endocrinol  2019; 11(1): 34-40.
 [http://dx.doi.org/10.4274/jcrpe.galenos.2018.2018.0121] [PMID: 30282619]

[29]
Kim YM, Jang YY, Jeong JE, Park HJ, Jang JH, Kim JK. A case of vitamin D hydroxylation-deficient rickets type 1A caused by 2 novel pathogenic variants in CYP27B1 gene. Ann Pediatr Endocrinol Metab  2019; 24(2): 137-41.
 [http://dx.doi.org/10.6065/apem.2019.24.2.137] [PMID: 31261480]

[30]
Li Y, Yuan X, Chen R, et al. Clinical and genetic analysis of two Chinese families with vitamin D-dependent rickets type IA and follow-up. Orphanet J Rare Dis  2020; 15(1): 273.
 [http://dx.doi.org/10.1186/s13023-020-01558-7] [PMID: 33004071]

[31]
Smith SJ, Rucka AK, Berry JL, et al. Novel mutations in the 1alpha-hydroxylase (P450c1) gene in three families with pseudovitamin D-deficiency rickets resulting in loss of functional enzyme activity in blood-derived macrophages. J Bone Miner Res  1999; 14(5): 730-9.
 [http://dx.doi.org/10.1359/jbmr.1999.14.5.730] [PMID: 10320521]

[32]
Chen H, Hewison M, Adams JS. Functional characterization of heterogeneous nuclear ribonuclear protein C1/C2 in vitamin D resistance: A novel response element-binding protein. J Biol Chem  2006; 281(51): 39114-20.
 [http://dx.doi.org/10.1074/jbc.M608006200] [PMID: 17071612]

[33]
Feldman D, J Malloy P. Mutations in the vitamin D receptor and hereditary vitamin D-resistant rickets. Bonekey Rep  2014; 3: 510.
 [http://dx.doi.org/10.1038/bonekey.2014.5] [PMID: 24818002]

[34]
Christakos S. Recent advances in our understanding of 1,25-dihydroxyvitamin D3 regulation of intestinal calcium absorption. Arch Biochem Biophys  2012; 523(1): 73-6.
 [http://dx.doi.org/10.1016/j.abb.2011.12.020] [PMID: 22230327]

[35]
Isojima T, Ishizawa M, Yoshimura K, et al. Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) caused by a VDR mutation: A novel mechanism of dominant inheritance. Bone Rep  2015; 2: 68-73.
 [http://dx.doi.org/10.1016/j.bonr.2015.05.001] [PMID: 28377956]

[36]
Zhou Y, Wang J, Malloy PJ, Dolezel Z, Feldman D. Compound heterozygous mutations in the vitamin D receptor in a patient with heredi-tary 1,25-dihydroxyvitamin D-resistant rickets with alopecia. J Bone Miner Res  2009; 24(4): 643-51.
 [http://dx.doi.org/10.1359/jbmr.081216] [PMID: 19049339]

[37]
Malloy PJ, Zhou Y, Wang J, Hiort O, Feldman D. Hereditary vitamin D-resistant rickets (HVDRR) owing to a heterozygous mutation in the vitamin D receptor. J Bone Miner Res  2011; 26(11): 2710-8.
 [http://dx.doi.org/10.1002/jbmr.484] [PMID: 21812032]

[38]
Malloy PJ, Tasic V, Taha D, et al. Vitamin D receptor mutations in patients with hereditary 1,25-dihydroxyvitamin D-resistant rickets. Mol Genet Metab  2014; 111(1): 33-40.
 [http://dx.doi.org/10.1016/j.ymgme.2013.10.014] [PMID: 24246681]

[39]
Ben Ameur S, Silve C, Chabchoub I, et al. Clinical and genetic characterization of tunisian children with hereditary 1,25-dihydroxyvitamin D-resistant rickets. Horm Res Paediatr  2017; 87(1): 23-9.
 [http://dx.doi.org/10.1159/000452886] [PMID: 28013309]

[40]
Faiyaz-Ul-Haque M, AlDhalaan W, AlAshwal A, et al. Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR): Clinical heteroge-neity and long-term efficacious management of eight patients from four unrelated Arab families with a loss of function VDR mutation. J Pediatr Endocrinol Metab  2018; 31(8): 861-8.
 [http://dx.doi.org/10.1515/jpem-2017-0312] [PMID: 29949513]

[41]
Arita K, Nanda A, Wessagowit V, Akiyama M, Alsaleh QA, McGrath JA. A novel mutation in the VDR gene in hereditary vitamin D-resistant rickets. Br J Dermatol  2008; 158(1): 168-71.
 [PMID: 17970811]

[42]
Ersoy B, Kiremitci S, Isojima T, Kitanaka S. Successful intermittent intravenous calcium treatment via the peripheral route in a patient with hereditary vitamin D-resistant rickets and alopecia. Horm Res Paediatr  2015; 83(1): 67-72.
 [http://dx.doi.org/10.1159/000367711] [PMID: 25573344]

[43]
Ma NS, Malloy PJ, Pitukcheewanont P, Dreimane D, Geffner ME, Feldman D. Hereditary vitamin D resistant rickets: Identification of a novel splice site mutation in the vitamin D receptor gene and successful treatment with oral calcium therapy. Bone  2009; 45(4): 743-6.
 [http://dx.doi.org/10.1016/j.bone.2009.06.003] [PMID: 19523546]

[44]
Abalı S, Tamura M, Turan S, et al. Hereditary vitamin D-resistant rickets: A report of four cases with two novel variants in the VDR gene and successful use of intermittent intravenous calcium via a peripheral route. J Pediatr Endocrinol Metab  2020; 33(4): 557-62.
 [http://dx.doi.org/10.1515/jpem-2019-0466] [PMID: 32049653]

[45]
Lucas J, Badia JL, Lucas E, Remon A. Cinacalcet treatment experience in hereditary vitamin D resistant rickets. J Pediatr Endocrinol Metab  2020; 33(2): 313-8.
 [http://dx.doi.org/10.1515/jpem-2019-0258] [PMID: 31926093]

[46]
Nicolescu RC, Lombet J, Cavalier E. Vitamin D-resistant rickets and cinacalcet—one more favorable experience. Front Pediatr  2018; 6: 376.
 [http://dx.doi.org/10.3389/fped.2018.00376] [PMID: 30555810]

[47]
Gardezi SA, Nguyen C, Malloy PJ, Posner GH, Feldman D, Peleg S. A rationale for treatment of hereditary vitamin D-resistant rickets with analogs of 1 alpha,25-dihydroxyvitamin D(3). J Biol Chem  2001; 276(31): 29148-56.
 [http://dx.doi.org/10.1074/jbc.M100898200] [PMID: 11369766]

[48]
Saponaro F, Saba A, Zucchi R. An update on vitamin D metabolism. Int J Mol Sci  2020; 21(18): 6573.
 [http://dx.doi.org/10.3390/ijms21186573] [PMID: 32911795]

[49]
Roizen JD, Li D, O’Lear L, et al. CYP3A4 mutation causes vitamin D-dependent rickets type 3. J Clin Invest  2018; 128(5): 1913-8.
 [http://dx.doi.org/10.1172/JCI98680] [PMID: 29461981]

[50]
Ho BB, Bergwitz C. FGF23 signalling and physiology. J Mol Endocrinol  2021; 66(2): R23-32.
 [http://dx.doi.org/10.1530/JME-20-0178] [PMID: 33338030]

[51]
Marks J, Debnam ES, Unwin RJ. Phosphate homeostasis and the renal-gastrointestinal axis. Am J Physiol Renal Physiol  2010; 299(2): F285-96.
 [http://dx.doi.org/10.1152/ajprenal.00508.2009] [PMID: 20534868]

[52]
Beck-Nielsen SS, Mughal Z, Haffner D, et al. FGF23 and its role in X-linked hypophosphatemia-related morbidity. Orphanet J Rare Dis  2019; 14(1): 58.
 [http://dx.doi.org/10.1186/s13023-019-1014-8] [PMID: 30808384]

[53]
Gaucher C, Walrant-Debray O, Nguyen TM, Esterle L, Garabédian M, Jehan F. PHEX analysis in 118 pedigrees reveals new genetic clues in hypophosphatemic rickets. Hum Genet  2009; 125(4): 401-11.
 [http://dx.doi.org/10.1007/s00439-009-0631-z] [PMID: 19219621]

[54]
Lin X, Li S, Zhang Z, Yue H. Clinical and genetic characteristics of 153 Chinese patients with x-linked hypophosphatemia. Front Cell Dev Biol  2021; 9: 617738.
 [http://dx.doi.org/10.3389/fcell.2021.617738] [PMID: 34141703]

[55]
Zheng B, Wang C, Chen Q, et al. Functional characterization of PHEX gene variants in children with X ‐linked hypophosphatemic rickets shows no evidence of genotype-phenotype correlation. J Bone Miner Res  2020; 35(9): 1718-25.
 [http://dx.doi.org/10.1002/jbmr.4035] [PMID: 32329911]

[56]
Park PG, Lim SH, Lee H, Ahn YH, Cheong HI, Kang HG. Genotype and phenotype analysis in x-linked hypophosphatemia. Front Pediatr  2021; 9: 699767.
 [http://dx.doi.org/10.3389/fped.2021.699767] [PMID: 34434907]

[57]
Baroncelli GI, Mora S. X-linked hypophosphatemic rickets: Multisystemic disorder in children requiring multidisciplinary management. Front Endocrinol  2021; 12: 688309.
 [http://dx.doi.org/10.3389/fendo.2021.688309] [PMID: 34421819]

[58]
Vega RA, Opalak C, Harshbarger RJ, et al. Hypophosphatemic rickets and craniosynostosis: A multicenter case series. J Neurosurg Pediatr  2016; 17(6): 694-700.
 [http://dx.doi.org/10.3171/2015.10.PEDS15273] [PMID: 26824597]

[59]
Houillier P, Salles JP. Biochemical assessment of phosphate homeostasis. Arch Pediatr  2021; 28(7): 588-93.
 [http://dx.doi.org/10.1016/j.arcped.2021.09.001] [PMID: 34598836]

[60]
Drezner MK, Lyles KW, Haussler MR, Harrelson JM. Evaluation of a role for 1,25-dihydroxyvitamin D3 in the pathogenesis and treat-ment of X-linked hypophosphatemic rickets and osteomalacia. J Clin Invest  1980; 66(5): 1020-32.
 [http://dx.doi.org/10.1172/JCI109930] [PMID: 6253520]

[61]
Haffner D, Emma F, Eastwood DM, et al. Clinical practice recommendations for the diagnosis and management of X-linked hypophos-phataemia. Nat Rev Nephrol  2019; 15(7): 435-55.
 [http://dx.doi.org/10.1038/s41581-019-0152-5] [PMID: 31068690]

[62]
White KE, Evans WE, O’Riordan JLH, et al. Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet  2000; 26(3): 345-8.
 [http://dx.doi.org/10.1038/81664] [PMID: 11062477]

[63]
Shimada T, Muto T, Urakawa I, et al. Mutant FGF-23 responsible for autosomal dominant hypophosphatemic rickets is resistant to prote-olytic cleavage and causes hypophosphatemia in vivo. Endocrinology  2002; 143(8): 3179-82.
 [http://dx.doi.org/10.1210/endo.143.8.8795] [PMID: 12130585]

[64]
White KE, Carn G, Lorenz-Depiereux B, Benet-Pages A, Strom TM, Econs MJ. Autosomal-dominant hypophosphatemic rickets (ADHR) mutations stabilize FGF-23. Kidney Int  2001; 60(6): 2079-86.
 [http://dx.doi.org/10.1046/j.1523-1755.2001.00064.x] [PMID: 11737582]

[65]
Mameli C, Sangiorgio A, Colombo V, et al. Autosomal dominant hypophosphatemic rickets: A case report and review of the literature. Int J Environ Res Public Health  2021; 18(16): 8771.
 [http://dx.doi.org/10.3390/ijerph18168771] [PMID: 34444516]

[66]
Gribaa M, Younes M, Bouyacoub Y, et al. An autosomal dominant hypophosphatemic rickets phenotype in a Tunisian family caused by a new FGF23 missense mutation. J Bone Miner Metab  2010; 28(1): 111-5.
 [http://dx.doi.org/10.1007/s00774-009-0111-5] [PMID: 19655082]

[67]
Sandal S, Arora V, Verma IC. Hypophosphatemic rickets with R179W mutation in FGFR23 gene - a rare but treatable cause of refractory rickets. Indian J Pediatr  2021; 88(1): 61-3.
 [http://dx.doi.org/10.1007/s12098-020-03335-7] [PMID: 32415663]

[68]
Liu C, Zhao Z, Wang O, et al. Earlier onset in autosomal dominant hypophosphatemic rickets of R179 than R176 mutations in fibroblast growth factor 23: Report of 20 Chinese cases and review of the literature. Calcif Tissue Int  2019; 105(5): 476-86.
 [http://dx.doi.org/10.1007/s00223-019-00597-y] [PMID: 31486862]

[69]
Kapelari K, Köhle J, Kotzot D, Högler W. Iron supplementation associated with loss of phenotype in autosomal dominant hypophos-phatemic rickets. J Clin Endocrinol Metab  2015; 100(9): 3388-92.
 [http://dx.doi.org/10.1210/jc.2015-2391] [PMID: 26186302]

[70]
Liu C, Li X, Zhao Z, et al. Iron deficiency plays essential roles in the trigger, treatment, and prognosis of autosomal dominant hypophos-phatemic rickets. Osteoporos Int  2021; 32(4): 737-45.
 [http://dx.doi.org/10.1007/s00198-020-05649-w] [PMID: 32995940]

[71]
Imel EA, Liu Z, Coffman M, Acton D, Mehta R, Econs MJ. Oral iron replacement normalizes fibroblast growth factor 23 in iron‐deficient patients with autosomal dominant hypophosphatemic rickets. J Bone Miner Res  2020; 35(2): 231-8.
 [http://dx.doi.org/10.1002/jbmr.3878] [PMID: 31652009]

[72]
Lorenz-Depiereux B, Bastepe M, Benet-Pagès A, et al. DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone ma-trix protein in the regulation of phosphate homeostasis. Nat Genet  2006; 38(11): 1248-50.
 [http://dx.doi.org/10.1038/ng1868] [PMID: 17033625]

[73]
Mäkitie O, Pereira RC, Kaitila I, et al. Long-term clinical outcome and carrier phenotype in autosomal recessive hypophosphatemia caused by a novel DMP1 mutation. J Bone Miner Res  2010; 25(10): 2165-74.
 [http://dx.doi.org/10.1002/jbmr.105] [PMID: 20499351]

[74]
Feng JQ, Ward LM, Liu S, et al. Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism. Nat Genet  2006; 38(11): 1310-5.
 [http://dx.doi.org/10.1038/ng1905] [PMID: 17033621]

[75]
Levy-Litan V, Hershkovitz E, Avizov L, et al. Autosomal-recessive hypophosphatemic rickets is associated with an inactivation mutation in the ENPP1 gene. Am J Hum Genet  2010; 86(2): 273-8.
 [http://dx.doi.org/10.1016/j.ajhg.2010.01.010] [PMID: 20137772]

[76]
Höppner J, Kornak U, Sinningen K, Rutsch F, Oheim R, Grasemann C. Autosomal recessive hypophosphatemic rickets type 2 (ARHR2) due to ENPP1-deficiency. Bone  2021; 153: 116111.
 [http://dx.doi.org/10.1016/j.bone.2021.116111] [PMID: 34252603]

[77]
Brachet C, Mansbach AL, Clerckx A, Deltenre P, Heinrichs C. Hearing loss is part of the clinical picture of ENPP1 loss of function muta-tion. Horm Res Paediatr  2014; 81(1): 63-6.
 [http://dx.doi.org/10.1159/000354661] [PMID: 24216977]

[78]
Kotwal A, Ferrer A, Kumar R, et al. Clinical and biochemical phenotypes in a family with ENPP1 mutations. J Bone Miner Res  2020; 35(4): 662-70.
 [http://dx.doi.org/10.1002/jbmr.3938] [PMID: 31826312]

[79]
Kinoshita Y, Hori M, Taguchi M, Fukumoto S. Functional analysis of mutant FAM20C in Raine syndrome with FGF23-related hypophos-phatemia. Bone  2014; 67: 145-51.
 [http://dx.doi.org/10.1016/j.bone.2014.07.009] [PMID: 25026495]

[80]
Seidahmed MZ, Alazami AM, Abdelbasit OB, et al. Report of a case of Raine syndrome and literature review. Am J Med Genet A  2015; 167(10): 2394-8.
 [http://dx.doi.org/10.1002/ajmg.a.37159] [PMID: 25974638]

[81]
Faundes V, Castillo-Taucher S, Gonzalez-Hormazabal P, Chandler K, Crosby A, Chioza B. Raine syndrome: An overview. Eur J Med Genet  2014; 57(9): 536-42.
 [http://dx.doi.org/10.1016/j.ejmg.2014.07.001] [PMID: 25019372]

[82]
Rafaelsen SH, Raeder H, Fagerheim AK, et al. Exome sequencing reveals FAM20c mutations associated with fibroblast growth factor 23-related hypophosphatemia, dental anomalies, and ectopic calcification. J Bone Miner Res  2013; 28(6): 1378-85.
 [http://dx.doi.org/10.1002/jbmr.1850] [PMID: 23325605]

[83]
Mameli C, Zichichi G, Mahmood N, et al. Natural history of non-lethal Raine syndrome during childhood. Orphanet J Rare Dis  2020; 15(1): 93.
 [http://dx.doi.org/10.1186/s13023-020-01373-0] [PMID: 32299476]

[84]
Eltan M, Alavanda C, Yavas Abali Z, et al. A rare cause of hypophosphatemia: Raine syndrome changing clinical features with age. Calcif Tissue Int  2020; 107(1): 96-103.
 [http://dx.doi.org/10.1007/s00223-020-00694-3] [PMID: 32337609]

[85]
White KE, Cabral JM, Davis SI, et al. Mutations that cause osteoglophonic dysplasia define novel roles for FGFR1 in bone elongation. Am J Hum Genet  2005; 76(2): 361-7.
 [http://dx.doi.org/10.1086/427956] [PMID: 15625620]

[86]
Kuthiroly S, Yesodharan D, Ghosh A, White K, Nampoothiri S. Osteoglophonic dysplasia: Phenotypic and radiological clues. J Pediatr Genet  2017; 6(4): 247-51.
 [http://dx.doi.org/10.1055/s-0037-1602816] [PMID: 29147600]

[87]
Carpenter TO, Imel EA, Holm IA, Jan de Beur SM, Insogna KL. A clinician’s guide to X-linked hypophosphatemia. J Bone Miner Res  2011; 26(7): 1381-8.
 [http://dx.doi.org/10.1002/jbmr.340] [PMID: 21538511]

[88]
Al Juraibah F, Al Amiri E, Al Dubayee M, et al. Diagnosis and management of X-linked hypophosphatemia in children and adolescent in the Gulf Cooperation Council countries. Arch Osteoporos  2021; 16(1): 52.
 [http://dx.doi.org/10.1007/s11657-021-00879-9] [PMID: 33660084]

[89]
Carpenter TO, Whyte MP, Imel EA, et al. Burosumab therapy in children with x-linked hypophosphatemia. N Engl J Med  2018; 378(21): 1987-98.
 [http://dx.doi.org/10.1056/NEJMoa1714641] [PMID: 29791829]

[90]
Imel EA, Glorieux FH, Whyte MP, et al. Burosumab versus conventional therapy in children with X-linked hypophosphataemia: A ran-domised, active-controlled, open-label, phase 3 trial. Lancet  2019; 393(10189): 2416-27.
 [http://dx.doi.org/10.1016/S0140-6736(19)30654-3] [PMID: 31104833]

[91]
Levi M, Gratton E, Forster IC, et al. Mechanisms of phosphate transport. Nat Rev Nephrol  2019; 15(8): 482-500.
 [http://dx.doi.org/10.1038/s41581-019-0159-y] [PMID: 31168066]

[92]
Lorenz-Depiereux B, Benet-Pages A, Eckstein G, et al. Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3. Am J Hum Genet  2006; 78(2): 193-201.
 [http://dx.doi.org/10.1086/499410] [PMID: 16358215]

[93]
Dasgupta D, Wee MJ, Reyes M, et al. Mutations in SLC34A3/] NPT2c are associated with kidney stones and nephrocalcinosis. J Am Soc Nephrol  2014; 25(10): 2366-75.
 [http://dx.doi.org/10.1681/ASN.2013101085] [PMID: 24700880]

[94]
Tencza AL, Ichikawa S, Dang A, et al. Hypophosphatemic rickets with hypercalciuria due to mutation in SLC34A3/type IIc sodium-phosphate cotransporter: Presentation as hypercalciuria and nephrolithiasis. J Clin Endocrinol Metab  2009; 94(11): 4433-8.
 [http://dx.doi.org/10.1210/jc.2009-1535] [PMID: 19820004]

[95]
Mejia-Gaviria N, Gil-Peña H, Coto E, Pérez-Menéndez TM, Santos F. Genetic and clinical peculiarities in a new family with hereditary hypophosphatemic rickets with hypercalciuria: A case report. Orphanet J Rare Dis  2010; 5(1): 1.
 [http://dx.doi.org/10.1186/1750-1172-5-1] [PMID: 20074341]

[96]
Phulwani P, Bergwitz C, Jaureguiberry G, Rasoulpour M, Estrada E. Hereditary hypophosphatemic rickets with hypercalciuria and nephro-lithiasis-Identification of a novel SLC34A3/NaPi-IIc mutation. Am J Med Genet A  2011; 155(3): 626-33.
 [http://dx.doi.org/10.1002/ajmg.a.33832] [PMID: 21344632]

[97]
Gordon RJ, Li D, Doyle D, Zaritsky J, Levine MA. Digenic heterozygous mutations in SLC34A3 and SLC34A1 cause dominant hypo-phosphatemic rickets with hypercalciuria. J Clin Endocrinol Metab  2020; 105(7): 2392-400.
 [http://dx.doi.org/10.1210/clinem/dgaa217] [PMID: 32311027]

[98]
Turan I, Erdem S, Kotan LD, et al. Experience with the targeted next-generation sequencing in the diagnosis of hereditary hypophos-phatemic rickets. J Pediatr Endocrinol Metab  2021; 34(5): 639-48.
 [http://dx.doi.org/10.1515/jpem-2020-0624] [PMID: 33852231]

[99]
Cebeci AN, Zou M, BinEssa  HA, et al. Mutation of SGK3, a novel regulator of renal phosphate transport, causes autosomal dominant hypophosphatemic rickets. J Clin Endocrinol Metab  2020; 105(6): 1840-50.
 [http://dx.doi.org/10.1210/clinem/dgz260] [PMID: 31821448]

[100]
Trepiccione F, Capasso G. SGK3: A novel regulator of renal phosphate transport? Kidney Int  2011; 80(1): 13-5.
 [http://dx.doi.org/10.1038/ki.2011.60] [PMID: 21673735]

[101]
Hawkes CP, Li D, Hakonarson H, Meyers KE, Thummel KE, Levine MA. CYP3A4 induction by rifampin: An alternative pathway for vitamin D inactivation in patients with CYP24A1 mutations. J Clin Endocrinol Metab  2017; 102(5): 1440-6.
 [http://dx.doi.org/10.1210/jc.2016-4048] [PMID: 28324001]

[102]
Bertholet-Thomas A, Tram N, Dubourg L, Lemoine S, Molin A, Bacchetta J. Fluconazole as a new therapeutic tool to manage patients with NPTIIc (SLC34A3) mutation: A case report. Am J Kidney Dis  2019; 73(6): 886-9.
 [http://dx.doi.org/10.1053/j.ajkd.2018.12.026] [PMID: 30765103]

[103]
Thiele S, Werner R, Stubbe A, Hiort O, Hoeppner W. Validation of a next-generation sequencing (NGS) panel to improve the diagnosis of X-linked hypophosphataemia (XLH) and other genetic disorders of renal phosphate wasting. Eur J Endocrinol  2020; 183(5): 497-504.
 [http://dx.doi.org/10.1530/EJE-20-0275] [PMID: 33107440]

[104]
Beck-Nielsen SS, Brixen K, Gram J, Brusgaard K. Mutational analysis of PHEX, FGF23, DMP1, SLC34A3 and CLCN5 in patients with hypophosphatemic rickets. J Hum Genet  2012; 57(7): 453-8.
 [http://dx.doi.org/10.1038/jhg.2012.56] [PMID: 22695891]
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DOI https://dx.doi.org/10.2174/1573396319666221205123402	Print ISSN 1573-3963
Publisher Name Bentham Science Publisher	Online ISSN 1875-6336
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