The Difficult Diagnosis of Hypophosphatemic Rickets-A Review of 8 Clinical Cases
Clinical Medicine Research
Volume 9, Issue 5, September 2020, Pages: 97-102
Received: Aug. 3, 2020;
Accepted: Aug. 18, 2020;
Published: Sep. 14, 2020
Views 130 Downloads 73
Anna-Maria Borissova, Clinic of Endocrinology, University Hospital Sofiamed, Sofia, Bulgaria; Medical Faculty, Sofia University “Saint Kliment Ohridsky”, Sofia, Bulgaria
Yordan Vlahov, Clinic of Endocrinology, University Hospital Sofiamed, Sofia, Bulgaria; Medical Faculty, Sofia University “Saint Kliment Ohridsky”, Sofia, Bulgaria
Seiji Fukumoto, Department of Molecular Endocrinology, Fujii Memorial Institute of Medical Sciences, Tokushima University, Tokushima, Japan
Yuichiro Shimizu, Shimizu Clinic Akasaka, Minato-ku, Tokyo, Japan
Todor Zahariev, Clinic of Vascular and Endovascular Surgery, University Hospital “Saint Ekaterina”, Sofia, Bulgaria; Medical Faculty, Medical University, Sofia, Bulgaria
Valentin Govedarski, Clinic of Vascular and Endovascular Surgery, University Hospital “Saint Ekaterina”, Sofia, Bulgaria; Medical Faculty, Medical University, Sofia, Bulgaria
Svetoslav Dimitrov, Clinic of Vascular and Endovascular Surgery, University Hospital “Saint Ekaterina”, Sofia, Bulgaria; Medical Faculty, Medical University, Sofia, Bulgaria
Radina Ivanova, Medical Faculty, Medical University, Sofia, Bulgaria; Pathological Department, University Hospital Alexandrovsa, Sofia, Bulgaria
Milena Nikolova, Medical Faculty, Medical University, Sofia, Bulgaria; Clinic of Nephrology, University Hospital “Saint Ivan Rilski”, Sofia, Bulgaria
Boyana Trifonova, Clinic of Endocrinology, University Hospital Sofiamed, Sofia, Bulgaria; Medical Faculty, Sofia University “Saint Kliment Ohridsky”, Sofia, Bulgaria
Follow on us
Hypophosphatemic rickets is a rare, usually genetic disease associated with decreased phosphate reabsorption in the proximal renal tubule and vitamin D resistance. Several genetic mutations have been discovered, the most common being the X-linked PHEX mutation with high fibroblast growth factor 23 (FGF23) circulating levels. The hypophosphatemic type osteomalacia is usually hereditary or tumour-induced (TIO). In the past 20 years, we have discovered, treated and followed up overall 8 cases of the disease-3 women and 5 men, aged 18 to 52 years. In all patients the diagnostic process was long (a mean of 2-3 years) and involved multiple clinical consults, laboratory evaluations: Biochemical Standard Research, Hormonal Tests [PTH, 25 (OH) D, 1,25 (OH) 2D], Specialized Research (FGF23), Instrumental Research (Ultrasonography of whole body; Computed tomography; Magnetic resonance imaging; DXA examination with an assessment of T-score and Z-score of spine/hip). All of these studies aimed at ruling out different neurological, hematological, oncological, rheumatic, gastroenterological, urological, nephrological diseases and conditions. One of the patients had Fanconi syndrome, five had X-linked hypophosphatemia (XLH) and two had TIO. In the last two patients, we found a high level of FGF23 secreting a small lung neoplasm in the first case and a mesenchymal tumor in the median upper part of the right thigh in the second case. The surgical removal of the tumor mass lead to a fast decrease in FGF23 levels and correction of metabolic disturbances. We present clinical cases with hypophosphatemic rickets/osteomalacia and discuss the etiopathogenesis and treatment of this rare disease. Historically until now phosphate supplementation and therapy using analogs of highly active vitamin D (calcitriol, alfacalcidol, paricalcitol) have been used to manage conditions involving hypophosphatemia. In recent years there has been a progression of clinical trials for monoclonal anti-FGF23 antibodies for the treatment of XLH. These monoclonal anti-FGF23 antibodies may have potential for treating other conditions associated with FGF23 overactivity. However, clinical trials to support that possibility are not available at present.
Hypophosphatemic Rickets, FGF23, Hereditary Forms, Mesenchymal Tumour, Treatment
To cite this article
The Difficult Diagnosis of Hypophosphatemic Rickets-A Review of 8 Clinical Cases, Clinical Medicine Research.
Vol. 9, No. 5,
2020, pp. 97-102.
Copyright © 2020 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/
) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Xianglan H. (2013). FGF23 and Phophate Wasting Disorders, Bone Research. 2, 120-132.
ADHR Consortium. (2000). Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet. 26: 345-348.
Pettifor JM, Thandrayen K. (2012). Hypophosphatemic rickets: unraveling the role of FGF23. Calcif Tissue Int. 91: 297-306.
Carpenter T. O, Imel E. A, Ruppe M. D, Webwr T. J, Klausner M. A, Wooddell M. M, Kawakami T, Ito T, Zhang X, Humphrey J, Insogna K. L, Peacock M. (2014). Randomized trial of the anti-FGF23 antibody KRN23 in X-linked hypophosphatemia. The Journal of Clinical Investigation. 24; 1587-1597.
Rayamajhi SJ, Yeh R, Wong T, Dumeer S, Mittal BR, Remotti F, Chikeka I, Reddy AK. (2019). Tumor-induced osteomalacia-Current imaging modalities and a systematic approach for tumor localization. Clin Imaging. Jul-Aug; 56: 114-123. doi: 10.1016/j.clinimag.2019.04.007. Epub 2019 Apr 17.
Bianchine JW, Stambler AA, Harrison HE. (1971). Familial Hypophosphatemia rickets showing autosomal domine inheritance. Birth Defects Orig Artic Ser. 7: 287-295.
Farrow EG, White KE. (2009). Tumor-induced osteomalacia. Expert Rev Endocrinol Metab. 4: 435-442.
Karatzas A, Paridis D, Kozyrakis D, Tzortzis V, Samarinas, Dailiana Z, Karachalios T. (2017). Fanconi syndrome in the adulthood. The role of early diagnosis and treatment. J Musculoskelet Neuronal Interact. 17 (4): 303-306.
Portale A. A, Carpenter T. O, Brandi M. L, Briot K. Cheong H. II, Cohen-Solal M, Crowley R, De Beur S. J, Eastell R, Imanishi Y, Imel E. A, Ing S, Ito N. et al. (2019). 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. Calcified Tissue International. 105: 271–284.
Noriko Oyama, Kanako Kojima-Ishii, Naoko Toda, Terumichi Matsuo, Vlad Tocan, Kazuhiro Ohkubo, Utako Oba, Yuhki Koga, Nokitaka Setsu, Yuichi Yamada, Kenichi Kohashi, Yasuharu Nakashima, Yoshinao Oda, Kenji Ihara, and Shouichi Ohga. (2020). Malignant transformation of phosphaturic mesenchymal tumor: a case report and literature review.
Weidner N, Santa CD. (1987). Phosphaturic mesenchymal tumors. Cancer. 59: 1442-1454.
Folpe AL, Fanburg-Smith JC, Billings SD, Bisceglia M, Bertoni F, Cho J. Y, Econs M. J. et al. (2004). Most osteomalacia associated mesenchymal tumors are a single histopathological entity. Am J Surg Pathol. 28: 1-30.
Chong WH, Molinolo AA, Chen CC, Collins MT. (2011). Tumor-induced osteomalacia. Endocr Relat Cancer. 18 (3): R53–R77. doi: 10.1530/ERC-11-0006.
Colangelo L, Pepe J, Nieddu L, Sonato C, Scillitani A, Diacinti D, Angelozzi M, Cipriani C, Minisola S. (2020). Long-term bone mineral density changes after surgical cure of patients with tumor-induced osteomalacia. Osteoporos Int. 31 (7): 1383-1387. doi: 10.1007/s00198-020-05369-1. Epub 2020 Mar 17.
Imel E. A, Biggin A, Schindeler A, Munns C. F. (2019). FGF23, Hypophosphatemia, and Emerging Treatments. JBMR1 Plus (WOA), 3, 8, e10190.
Athonvarangkul D, Insogna KL. (2020). New Therapies for Hypophosphatemia-Related to FGF23 Excess. Calcif Tissue Int. Jun 5. doi: 10.1007/s00223-020-00705-3.
Florenzano P, Hartley IR, Jimenez M, Roszko K, Gafni RI, Collins MT. (2020). Tumor-Induced Osteomalacia. Calcif Tissue Int. Jun 5. doi: 10.1007/s00223-020-00691-6.