Download PDF
CC BY-NC-ND 4.0 · Horm Metab Res 2023; 55(10): 653-664
DOI: 10.1055/a-2159-8429
Review

X-Linked Familial Hypophosphatemia: A Case Report of 27-Year Old Male and Review of Literature

Shadan Jabbar Abdullah
1   Endocrine Unit, Internal Medicine, Shar Hospital, Sulaymaniyah, Kurdistan region, Iraq
,
Taha Othman Mahwi
2   Medicine, University of Sulaimani College of Medicine, Sulaymaniyah, Kurdistan region, Iraq
,
Areewan Mohamad Salih Saeed
3   Surgery, University of Sulaimani College of Medicine, Sulaymaniyah, Kurdistan region, Iraq
,
Darya Saeed Abdulateef 
4   Medical Education, University of Sulaimani College of Medicine, Sulaymaniyah, Kurdistan region, Iraq
,
Heshu Sulaiman Rahman
5   Physiology, University of Sulaimani College of Medicine, Sulaymaniyah, Kurdistan region, Iraq
,
Shaho Fatah Ahmed
1   Endocrine Unit, Internal Medicine, Shar Hospital, Sulaymaniyah, Kurdistan region, Iraq
,
Sarkan Ahmed Abdulqader
6   Orthopedic Surgery Unit, Shar Hospital, Sulaymaniyah, Kurdistan region, Iraq
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

Abstract

X-linked hypophosphatemia (XLH) associated with short stature during childhood are mostly referred to the hospital and diagnosed as vitamin D deficiency rickets and received vitamin D before adulthood. A case is presented with clinical features of hypophosphatemia from childhood who did not seek medical care for diagnosis and treatment, nor did his mother or two brothers, who have short statures, bone pain, and fractures. The patient was assessed for sociodemographic, hematological, and biochemical parameters together with a genetic assessment. A DEXA scan and X-ray were done to determine the abnormalities and deformities of joints and bones despite clinical examination by an expert physician. All imaging, laboratory parameters, and the genetic study confirmed the diagnosis of XLH. A detailed follow-up of his condition was performed after the use of phosphate tablets and other treatments. X-linked hypophosphatemia needs a good assessment, care, and follow up through a complementary medical team including several specialties. Phosphate tablets in adulthood significantly affects clinical and physical improvement and prevention of further skeletal abnormality and burden on daily activity. The patients should be maintained with an adequate dose of phosphate for better patient compliance. More awareness is needed in society and for health professionals when conducting medical checkups during the presence of stress fractures, frequent dental and gum problems, rickets, short stature, or abnormality in the skeleton or walking to think of secondary causes such as hypophosphatemia. Further investigations including a visit to a specialist is imperative to check for the primary cause of these disturbances.

Key words

inherited disorders - rare disease - PHEX gene mutation - adult

Additional material



Publication History

Received: 16 January 2023

Accepted after revision: 15 August 2023

Article published online:
09 October 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Hall J. Parathyroid hormone, calcitonin, calcium and phosphate metabolism, vitamin D, bone, and teeth. Chapter 80. In: Guyton and Hall Textbook of Medical Physiology. Elsevier; 2021: 991-992
    Search in Google Scholar
  • 2 Bacchetta J, Salusky IB. Evaluation of hypophosphatemia: lessons from patients with genetic disorders. Am J Kidney Dis 2012; 59: 152
    CrossrefPubMedSearch in Google Scholar
  • 3 Meng QH, Wagar EA. Severe hypophosphatemia in a 79-year-old man. Clin Chem 2014; 60: 928-931
    CrossrefPubMedSearch in Google Scholar
  • 4 Lederer E. Hypophosphatemia: background, pathophysiology, epidemiology. Medscape 2020; Editor Vecihi Batuman. In Internet: https://emedicine.medscape.com/article/242280-overview
    PubMed
  • 5 Schwartz RS, Prié D, Friedlander G. Mechanisms of disease genetic disorders of renal phosphate transport. 2010
    PubMed
  • 6 Block GA, Bushinsky DA, Cunningham J. et al. Effect of etelcalcetide vs placebo on serum parathyroid hormone in patients receiving hemodialysis with secondary hyperparathyroidism two randomized clinical trials supplemental content. TRIAL Regist Clin Identifiers 2017; 317: 146-155
    PubMedSearch in Google Scholar
  • 7 Clinkenbeard E, White K. Systemic control of bone homeostasis by FGF23 signaling. Curr Mol Biol Rep 2016; 2: 62-71
    CrossrefPubMedSearch in Google Scholar
  • 8 Francis F, Hennig S, Korn B. et al. A gene (PEX) with homologies to endopeptidases is mutated in patients with X–linked hypophosphatemic rickets. Nat Genet 1995; 11: 130-136
    CrossrefPubMedSearch in Google Scholar
  • 9 White KE, Evans WE, O’Riordan JLH. et al. Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet 2000; 26: 345-348
    CrossrefPubMedSearch in Google Scholar
  • 10 Lorenz-Depiereux B, Bastepe M, Benet-Pagès A. et al. DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis. Nat Genet 2006; 38: 1248-1250
    CrossrefPubMedSearch in Google Scholar
  • 11 Forero-Delgadillo JM, Cleves D, Ochoa V. et al. PHEX gene mutation in a patient with X-linked hypophosphatemic rickets in a developing country. Appl Clin Genet 2020; 13: 57
    CrossrefPubMedSearch in Google Scholar
  • 12 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
    PubMedSearch in Google Scholar
  • 13 Whyte MP, Schranck FW, Armamento-Villareal R. X-linked hypophosphatemia: a search for gender, race, anticipation, or parent of origin effects on disease expression in children. J Clin Endocrinol Metab 1996; 81: 4075-4080
    PubMedSearch in Google Scholar
  • 14 Skrinar A, Dvorak-Ewell M, Evins A. et al. The lifelong impact of X-linked hypophosphatemia: results from a burden of disease survey. J Endocr Soc 2019; 3: 1321-1334
    CrossrefPubMedSearch in Google Scholar
  • 15 Chan JC. Hypophosphatemic rickets clinical presentation: history, physical examination. Medscape 2020; Editor: Sasigarn A. Bowden. In Internet: https://emedicine.medscape.com/article/922305-clinical#b3
    PubMed
  • 16 Carpenter TO, Imel EA, Holm IA. et al. A clinician’s guide to X-linked hypophosphatemia. J Bone Miner Res 2011; 26: 1381-1388
    CrossrefPubMedSearch in Google Scholar
  • 17 Dahir K, Roberts MS, Krolczyk S. et al. X-linked hypophosphatemia: a new era in management. J Endocr Soc 2020; 4: 1-15
    CrossrefPubMedSearch in Google Scholar
  • 18 Pettifor JM. What’s new in hypophosphataemic rickets?. Eur J Pediatr 2008; 167: 493-499
    CrossrefPubMedSearch in Google Scholar
  • 19 Foster BL, Ramnitz MS, Gafni RI. et al. Rare bone diseases and their dental, oral, and craniofacial manifestations. J Dent Res 2014; 93: 7S-19S
    CrossrefPubMedSearch in Google Scholar
  • 20 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
    CrossrefPubMedSearch in Google Scholar
  • 21 Che H, Roux C, Etcheto A. et al. Impaired quality of life in adults with X-linked hypophosphatemia and skeletal symptoms. Eur J Endocrinol 2016; 174: 325-333
    CrossrefPubMedSearch in Google Scholar
  • 22 Lecoq AL, Brandi ML, Linglart A. et al. Management of X-linked hypophosphatemia in adults. Metabolism 2020; 103: 154049
    CrossrefPubMedSearch in Google Scholar
  • 23 Quinlan C, Guegan K, Offiah A. et al. Growth in PHEX-associated X-linked hypophosphatemic rickets: the importance of early treatment. Pediatr Nephrol 2012; 27: 581-588
    CrossrefPubMedSearch in Google Scholar
  • 24 Whyte MP, Carpenter TO, Gottesman GS. et al. Efficacy and safety of burosumab in children aged 1-4 years with X-linked hypophosphataemia: a multicentre, open-label, phase 2 trial. lancet Diabetes Endocrinol 2019; 7: 189-199
    CrossrefPubMedSearch in Google Scholar
  • 25 Rafaelsen S, Johansson S, Ræder H. et al. Hereditary hypophosphatemia in Norway: a retrospective population-based study of genotypes, phenotypes, and treatment complications. Eur J Endocrinol 2015; 174: 125
    PubMedSearch in Google Scholar
  • 26 Al Kaissi A, Farr S, Ganger R. et al. Windswept lower limb deformities in patients with hypophosphataemic rickets. Swiss Med Wkly 2013; 143: 1-7
    PubMedSearch in Google Scholar
  • 27 Dagi Glass LR, Forcht Dagi T, Dagi LR. Papilledema in the setting of x-linked hypophosphatemic rickets with craniosynostosis. Case Rep Ophthalmol 2011; 2: 376-381
    CrossrefPubMedSearch in Google Scholar
  • 28 Dahir K, Roberts MS, Krolczyk S. et al. X-Linked Hypophosphatemia: a new era in management. J Endocr Soc 2020; 4: 1-15
    CrossrefPubMedSearch in Google Scholar
  • 29 Beck-Nielsen SS, Brusgaard K, Rasmussen LM. et al. Phenotype presentation of hypophosphatemic rickets in adults. Calcif Tissue Int 2010; 87: 108-119
    CrossrefPubMedSearch in Google Scholar
  • 30 Steele A, Gonzalez R, Garbalosa JC. et al. Osteoarthritis, osteophytes, and enthesophytes affect biomechanical function in adults with X-linked hypophosphatemia. J Clin Endocrinol Metab 2020; 105: e1798
    CrossrefPubMedSearch in Google Scholar
  • 31 Veilleux LN, Cheung M, Ben Amor M. et al. Abnormalities in muscle density and muscle function in hypophosphatemic rickets. J Clin Endocrinol Metab 2012; 97
    PubMedSearch in Google Scholar
  • 32 Pesta DH, Tsirigotis DN, Befroy DE. et al. Hypophosphatemia promotes lower rates of muscle ATP synthesis. FASEB J 2016; 30: 3378-3387
    CrossrefPubMedSearch in Google Scholar
  • 33 Lambert AS, Zhukouskaya V, Rothenbuhler A. et al. X-linked hypophosphatemia: Management and treatment prospects. Joint Bone Spine 2019; 86: 731-738
    CrossrefPubMedSearch in Google Scholar
  • 34 Cho H, Lee B, Kang J. et al. A clinical and molecular genetic study of hypophosphatemic rickets in children. Pediatr Res 2005; 58: 329-333
    CrossrefPubMedSearch in Google Scholar
  • 35 Econs MJ, Samsa GP, Monger M. et al. X-Linked hypophosphatemic rickets: a disease often unknown to affected patients. Bone Miner 1994; 24: 17-24
    CrossrefPubMedSearch in Google Scholar
  • 36 Rothenbuhler A, Schnabel D, Högler W. et al. Diagnosis, treatment-monitoring and follow-up of children and adolescents with X-linked hypophosphatemia (XLH). Metabolism 2020; 103S:153892.
    CrossrefPubMedSearch in Google Scholar
  • 37 Holm IA, Econs MJ, Carpenter TO. Familial hypophosphatemia and related disorders. Pediatr Bone Biol Dis 2012; 699-726
    CrossrefPubMedSearch in Google Scholar
  • 38 Blackburn J, Ramakrishnan R. Short stature: making a crystal clear diagnosis. J Pediatr Endocrinol Metab 2019; 32: 1187-1191
    CrossrefPubMedSearch in Google Scholar
  • 39 Ribeiro TR, Costa FWG, Soares ECS. et al. Enamel and dentin mineralization in familial hypophosphatemic rickets: a micro-CT study. Dentomaxillofacial Radiol 2015; 44
    PubMedSearch in Google Scholar
  • 40 Carpenter TO. New perspectives on the biology and treatment of X-linked hypophosphatemic rickets. Pediatr Clin North Am 1997; 44: 443-466
    CrossrefPubMedSearch in Google Scholar
  • 41 Tavana N, Thilakavathy K, Kennerson ML. et al. Genetic basis of hereditary hypophosphataemic rickets and phenotype presentation in children and adults. Endokrynol Pol 2021; 72: 366-394
    CrossrefPubMedSearch in Google Scholar
  • 42 Hamdy NAT, Harvengt P, Usardi A. X-linked hypophosphatemia: The medical expert’s challenges and the patient’s concerns on their journey with the disease. Arch Pediatr 2021; 28: 612-618
    CrossrefPubMedSearch in Google Scholar
  • 43 Biosse Duplan M, Coyac BR, Bardet C. et al. Phosphate and Vitamin D Prevent Periodontitis in X-Linked Hypophosphatemia. J Dent Res 2017; 96: 388-395
    CrossrefPubMedSearch in Google Scholar
  • 44 Haffner D, Emma F, Eastwood DM. et al. Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia. Nat Rev Nephrol 2019 157 2019; 15: 435-455
    PubMedSearch in Google Scholar
  • 45 Fuente R, Gil-Peña H, Claramunt-Taberner D. et al. X-linked hypophosphatemia and growth. Rev Endocr Metab Disord 2017; 18: 107-115
    CrossrefPubMedSearch in Google Scholar
  • 46 Mäkitie O, Doria A, Kooh SW. et al. Early treatment improves growth and biochemical and radiographic outcome in X-linked hypophosphatemic rickets. J Clin Endocrinol Metab 2003; 88: 3591-3597
    CrossrefPubMedSearch in Google Scholar
  • 47 Rafaelsen S, Johansson S, Ræder H. et al. Hereditary hypophosphatemia in Norway: a retrospective population-based study of genotypes, phenotypes, and treatment complications. Eur J Endocrinol 2016; 174: 125-136
    CrossrefPubMedSearch in Google Scholar
  • 48 Misra M, Imel E, Chanoine J-P. et al. Clinical evidence for the benefits of burosumab therapy for X-linked hypophosphatemia (XLH) and other conditions in adults and children. Front Endocrinol 2020; 1: 338
    PubMedSearch in Google Scholar
  • 49 Portale AA, Carpenter TO, Brandi ML. et al. Continued beneficial effects of burosumab in adults with X-linked hypophosphatemia: results from a 24-week treatment continuation period after a 24-week double-blind placebo-controlled period. Calcif Tissue Int 2019; 105: 271-284
    CrossrefPubMedSearch in Google Scholar
  • 50 Gizard A, Rothenbuhler A, Pejin Z. et al. Outcomes of orthopedic surgery in a cohort of 49 patients with X-linked hypophosphatemic rickets (XLHR). Endocr Connect 2017; 6: 566-573
    CrossrefPubMedSearch in Google Scholar
  • 51 Ferizović N, Marshall J, Williams AE. et al. Exploring the burden of X-linked hypophosphataemia: an opportunistic qualitative study of patient statements generated during a technology appraisal. Adv Ther 2020; 37: 770-784
    CrossrefPubMedSearch in Google Scholar
  • 52 Seefried L, Smyth M, Keen R. et al. Burden of disease associated with X-linked hypophosphataemia in adults: a systematic literature review. Osteoporos Int 2021; 32: 7-22
    CrossrefPubMedSearch in Google Scholar
  • 53 Verge CF, Lam A, Simpson JM. et al. Effects of therapy in X-linked hypophosphatemic rickets. N Engl J M 2010; 325: 1843-1848
    CrossrefPubMedSearch in Google Scholar
  • 54 Radlović V, Smoljanić Ž, Radlović N. et al. X-linked hypophosphatemic rickets: Case report. Srp Arh Celok Lek 2014; 142: 75-78
    CrossrefPubMedSearch in Google Scholar
  • 55 Li J, Rai S, Ze R. et al. Rotational and translational osteotomy for treatment of severe deformity in hypophosphatemic rickets: a case report. Medicine (Baltimore) 2020; 99
    PubMedSearch in Google Scholar
  • 56 Areses-Trapote R, López-García JA, Ubetagoyena-Arrieta M. et al. Hereditary hypophosphatemic rickets with hypercalciuria: case report. Nefrologia 2012; 32: 529-534
    PubMedSearch in Google Scholar
  • 57 Maia M, Abreu ALS, Nogueira PCK. et al. Hypophosphatemic rickets: case report. Rev Paul Pediatr 2018; 36: 242
    PubMedSearch in Google Scholar
  • 58 Sarat G, Priyanka N, Prabhat MPV. et al. Hypophosphatemic rickets in siblings: a rare case report. Case Rep Dent 2016; 2016: 1-9
    PubMedSearch in Google Scholar
  • 59 Van Vuren AJ, Gaillard CAJM, Eisenga MF. et al. The EPO-FGF23 signaling pathway in erythroid progenitor cells: Opening a new area of research. Front Physiol 2019; 10: 304
    CrossrefPubMedSearch in Google Scholar