Four Cases of X-Linked Hypophosphatemic Rickets, Clinical Description and Genetic Testing

Abstract

One of the major causes of congenital hypophosphatemic rickets is the X-linked hypophosphatemic rickets (XHR), due to a defect on PHEX gene. The XHR increases the renal elimination of phosphate, that condition leads a defective mineralization of bones and also affects the growth in children. Clinical diagnosis should be suspected in children with signs of rickets and hypophosphatemia with normal calcium levels. We describe clinical characteristics and genetic results of four patients diagnosed and treated in our Nephrology Section. All patients have a de novo XHR as none familiars are affected. Early diagnosis should be suspected before the bone deformities have been submitted and the growth would have been impaired.

Share and Cite:

Vila-Pérez, D. , Marín-del-Barrio, S. , Vila-Cots, J. , Camacho-Díaz, J. , Morey, M. and Loidi, L. (2014) Four Cases of X-Linked Hypophosphatemic Rickets, Clinical Description and Genetic Testing. Open Journal of Genetics, 4, 40-45. doi: 10.4236/ojgen.2014.41006.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Quarles, L.D. (2003) Evidence for a Bone-Kidney Axis Regulating Phosphate Homeostasis. Journal of Clinical Investigation, 112, 642-646. http://dx.doi.org/10.1172/JCI200319687
[2] Rowe, O.S. (2000) The molecular background to hypophosphatemic rickets. Archives of Disease in Childhood, 83, 192-194. http://dx.doi.org/10.1136/adc.83.3.192
[3] Cho, H.Y., Lee, B.J., Kang, J.H., Ha, I.S., Cheong, H.I. and Choi, Y. (2005) A clinical and molecular genetic study of hypophosphatemic rickets in children. Pediatric Research, 58, 329-333.
http://dx.doi.org/10.1203/01.PDR.0000169983.40758.7B
[4] Bielesz, B., Klaushofer, K. and Oberbauer, R. (2004) Renal Phosphate Loss in Hereditary and Acquired Disorders of Bone Mineralization. Bone, 35, 1229-1239. http://dx.doi.org/10.1016/j.bone.2004.08.009
[5] Rowe, P. (2004) The Wrickkened Pathways of FGF-23, MEPE and PHEX. Critical Reviews in Oral Biology & Medicine, 15, 264-281. http://dx.doi.org/10.1177/154411130401500503
[6] de Beur, S.M.J. and Levine, M.A. (2002) Molecular Pathogenesis of Hypophosphatemic Rickets. The Journal of Clinical Endocrinology & Metabolism, 87, 2467-2473. http://dx.doi.org/10.1210/jcem.87.6.8688
[7] Saggese, G. and Baroncelli, G.I. (2000) Hypophosphatemic Rickets. Hormone Research in Paediatrics, 53, 57-60.
http://dx.doi.org/10.1159/000023535
[8] Chaussain-Miller, C., Sinding, C., Septier, D., Wolikow, M., Goldberg, M., et al. (2007) Dentin Structure in Familial Hypophosphatemic Rickets: Benefits of Vitamin D and Phosphate Treatment. Oral Diseases, 13, 482-489.
http://dx.doi.org/10.1111/j.1601-0825.2006.01326.x
[9] Wharton, B. and Bishop, N. (2003) Rickets. Lancet, 362, 1389-1400.
http://dx.doi.org/10.1016/S0140-6736(03)14636-3
[10] Root, A.W. and Diamond Jr., F.B. (2002) Disorders of Calcium Metabolism in the Child and Adolescent. In: Sperling M.A., Ed., Pediatric Endocrinology, 2nd Edition, Saunders, Philadelphia, 646.
[11] Garg, R.K. and Tandon, N. (1999) Hypophosphatemic Rickets: Easy to Diagnose, Difficult to Treat. Indian Journal of Pediatrics, 66, 849-857. http://dx.doi.org/10.1007/BF02723852
[12] Winters, R., Grahan, J., Williams, T., McFalls, V. and Burnett, C. (1958) A Genetic Study of Familial Hypophosphatemia and Vitamin D Resistant Rickets with a Review of the Literature. Medicine, 37, 97-142.
http://dx.doi.org/10.1097/00005792-195805000-00001
[13] Segawa, H., Kaneko, I., Takahashi, A., Kuwahata, M., Ito, M., Ohkido, I., et al. (2002) Growth-Related Renal Type II Na/Pi Cotransporter. The Journal of Biological Chemistry, 277, 19665-19672.
http://dx.doi.org/10.1074/jbc.M200943200
[14] Murer, H., Forster, I. and Biber, J. (2004) The Sodium Phosphate Cotransporter Family SLC34. Pflugers Arch, 447, 763-767. http://dx.doi.org/10.1007/s00424-003-1072-5
[15] Strewler, G.J. (2001) FGF23, Hypophosphatemia, and Rickets: Has Phosphatonin Been Found? Proceedings of the National Academy of Sciences of the United States of America, 98, 5945-5946.
http://dx.doi.org/10.1073/pnas.111154898
[16] Riminucci, M., Collins, M.T., Fedarko, N.S., Cherman, N., Corsi, A., White, K.E., et al. (2003) FGF-23 in Fibrous Dysplasia of Bone and Its Relationship to Renal Phosphate Wasting. The Journal of Clinical Investigation, 112, 683-692. http://dx.doi.org/10.1172/JCI18399
[17] Bowe, A.E., Finnegan, R., de Beur, S.M.J., Cho, J., Levine, M.A., Kumar, R., et al. (2001) FGF-23 Inhibits Renal Tubular Phosphate Transport and Is a PHEX Substrate. Biochemical and Biophysical Research Communications, 284, 977-981. http://dx.doi.org/10.1006/bbrc.2001.5084
[18] Dixon, P.H., Christie, P.T., Wooding, C., Trump, D., Grieff, M., Holm, I., et al. (1998) Mutational Analysis of PHEX Gene in X-Linked Hypophosphatemia. The Journal of Clinical Endocrinology & Metabolism, 83, 3615-3623.
[19] Yamazaki, Y., Okazaki, R., Shibata, M., Hasegawa, Y., Satoh, K., Tajima, T., Takeuchi, Y., Fujita, T., Nakahara, K., Yamashita, T. and Fukumoto, S. (2002) Increased Circulatory Level of Biologically Active Full-Length FGF-23 in Patients with Hypophosphatemic Rickets/Osteomalacia. The Journal of Clinical Endocrinology & Metabolism, 87, 4957-4960. http://dx.doi.org/10.1210/jc.2002-021105
[20] Rowe, P.S., Oudet, C.L., Francis, F., Sinding, C., Pannetier, S., Econs, M.J., Strom, T.M., Meitinger, T., Garabedian, M., David, A., Macher, M.A., Questiaux, E., Popowska, E., Pronicka, E., Read, A.P., Mokrzycki, A., Glorieux, F.H., Drezner, M.K., Hanauer, A., Lehrach, H., Goulding, J.N. and O’Riordan, J.L. (1997) Distribution of Mutations in the PEX Gene in Families with X-Linked Hypophosphataemic Rickets (HYP). Human Molecular Genetics, 6, 539-549.
http://dx.doi.org/10.1093/hmg/6.4.539
[21] Morey, M., Castro-Feijoo, L., Barreiro, J., Cabanas, P., Pombo, M., Gil, M., et al. (2011) Genetic Diagnosis of X-Linked Dominant Hypophosphstemic Rickets in a Cohort Study: Tubular Reabsorption of Phosphate and 1,25 (OH) 2D Serum Levels Are Asociated with PHEX Mutation Type. BMC Medical Genetics, 12, 116.
http://dx.doi.org/10.1186/1471-2350-12-116
[22] Alon, U.S., Levy-Olomucki, R., Moore, W.V., Stubbs, J., Liu, S. and Quarles, L.D. (2008) Calcimimetics as an Adjuvant Treatment for Familial Hypophosphatemic Rickets. Clinical Journal of the American Society of Nephrology, 3, 658-664. http://dx.doi.org/10.2215/CJN.04981107
[23] Yavropoulou, M.P., Kotsa, K., Gotzamani Psarrakou, A., Papazisi, A., Tranga, T., Ventis, S. and Yovos, J.G. (2010) Cinacalcet in Hyperparathyroidism Secondary to X-Linked Hypophosphatemic Rickets: Case Report and Brief Literature Review. Hormones (Athens), 9, 274-278. http://dx.doi.org/10.14310/horm.2002.1277
[24] Raeder, H., Shaw, N., Netelenbos, C. and Bjerknes, R. (2008) A Case of X-Linked Hypophosphatemic Rickets: Complications and the Therapeutic Use of Cinacalcet. European Journal of Endocrinology, S101-S105.
http://dx.doi.org/10.1530/EJE-08-0383
[25] Mäkitie, O., Doria, A., Kooh, S.W., Cole, W.G., Daneman, A. and Sochett, E. (2003) Early Treatment Improves Growth and Biochemical and Radiographic Outcome in X-Linked Hypophosphatemic Rickets. The Journal of Clinical Endocrinology & Metabolism, 88, 3591-3597. http://dx.doi.org/10.1210/jc.2003-030036
[26] Pereira, C.M., Andrade, C.R., Vargas, P.A., Coletta, R.D., Almeida, O.P. and Lopes, M.A. (2004) Dental Alterations Associated with X-Linked Hypophosphatemic Rickets. Journal of Endodontics, 30, 241-245.
http://dx.doi.org/10.1097/00004770-200404000-00015
[27] Chaussain-Miller, C., Sinding, C., Wolikow, M., Lasfargues, J.J., Godeau, G. and Garabédian, M. (2003) Dental Abnormalities in Patients with Familial Hypophosphatemic Vitamin D-Resistant Rickets: Prevention by Early Treatment with 1-Hydroxyvitamin D. The Journal of Pediatrics, 142, 324-331.http://dx.doi.org/10.1067/mpd.2003.119
[28] Haramati, A., Mulroney, S.E. and Lumpkin, M.D. (1990) Regulation of Renal Phosphate Reabsorption during Development: Implications from a New Model of Growth Hormone Deficiency. Pediatric Nephrology, 4, 387-391.
http://dx.doi.org/10.1007/BF00862524
[29] Brixen, K., Nielsen, H.K., Mosekilde, L. and Flyvbjerg, A. (1990) A Short Course of Recombinant Human Growth Hormone Treatment Stimulates Osteoblasts and Activates Bone Remodeling in Normal Human Volunteers. Journal of Bone and Mineral Research, 5, 609-618. http://dx.doi.org/10.1002/jbmr.5650050610
[30] Brixen, K., Nielsen, H.K., Bouillon, R., Flyvbjerg, A. and Mosekilde, L. (1992) Effects of Short-Term Growth Hormone Treatment on PTH, Calcitriol, Thyroid Hormones, Insulin and Glucagon. Acta Endocrinology, 127, 331-336.
[31] Baroncelli, G.I., Bertelloni, S., Ceccarelli, C. and Saggese, G. (2001) Effect of Growth Hormone Treatment on Final Height, Phosphate Metabolism, and Bone Mineral Density in Children with X-Linked Hypophosphatemic Rickets. Journal of Pediatrics, 138, 236-243. http://dx.doi.org/10.1067/mpd.2001.108955
[32] Seikaly, M.G. and Baum, M. (1995) Stimulation of Growth Hormone Secretion in Children with x-Linked Hypophosphatemia. Pediatric Nephrology, 9, 751-752. http://dx.doi.org/10.1007/BF00868733
[33] Seikaly, M.G., Brown, R. and Baum, M. (1997) The Effect of Recombinant Human Growth Hormone in Children with X-Linked Hypophosphatemia. Pediatrics, 100, 879-884. http://dx.doi.org/10.1542/peds.100.5.879
[34] Makitie, O., Toiviainen-Salo, S., Marttinen, E., Kaitila, I., Sochett, E. and Sipila, I. (2008) Metabolic Control and Growth during Exclusive Growth Hormone Treatment in X-Linked Hypophosphatemic Rickets. Hormone Research in Paediatrics, 69, 212-220. http://dx.doi.org/10.1159/000113021

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.