Phenotypes of a family with XLH with a novel PHEX mutation

Yamamoto, Akiko; Nakamura, Teruya; Ohata, Yasuhisa; Kubota, Takuo; Ozono, Keiichi

doi:10.1038/s41439-020-0095-1

Cited by 7 publications

(6 citation statements)

References 11 publications

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“…( 20 , 23 , 24 ) Although this introduces the possibility of error due to sex differences, studies with PHEX ‐mutation confirmed XLH have not identified such an effect. ( 24 , 25 ) This study also carries the same limitations of any retrospective analysis, such as ascertainment and recall bias, which may be implicated in the identification of XLH patients in the database used for this study. ( 26 ) As such, we recommend using the results of this study only to supplement standard diagnostic procedures until they are validated in a prospective, multicenter study.…”

Section: Discussionmentioning

confidence: 99%

Rare Diseases That Impersonate One Another:X‐LinkedHypophosphatemia andTumor‐InducedOsteomalacia, a Retrospective Analysis of Discriminating Features

et al. 2022

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Tumor‐induced osteomalacia (TIO) is a rare paraneoplastic disease characterized by frequent fractures, bone pain, muscle weakness, and affected gait. The rarity of TIO and similar presentation to other phosphate‐wasting disorders contribute to a high misdiagnosis rate and long time to correct diagnosis. TIO is curable by tumor resection, so accurate diagnosis has significant impact on patients' emotional and economic burden. Current diagnostics for TIO rely on decades‐old literature with poor phenotypic validation. Here, we identify salient clinical differences between rigorously validated cohorts of patients with TIO (n = 9) and X‐linked hypophosphatemia (XLH; n = 43), a frequent misdiagnosis for patients with TIO. The TIO cohort had significantly elevated FGF23 (365 versus 95 RU/mL, p < 0.001) and alkaline phosphatase (282.8 versus 118.5 IU/L, p < 0.01) but significantly reduced phosphorus (1.4 versus 2.2 mg/dL, p < 0.05) and 1,25(OH)2 D (16.6 versus 59.8 pg/mL, p < 0.01). By contrast, total vitamin D was similar between the two groups. Dual‐energy X‐ray absorptiometry (DXA) scans reveal lower Z‐scores in the hip (−1.6 versus 0.050, p < 0.01) and spine (0.80 versus 2.35, p < 0.05). TIO patients were more likely to have prior clinical diagnosis of osteoporosis (67% versus 0%), use assistive devices in daily living (100% versus 14%), and have received a knee arthroplasty (33% versus 7%). TIO patients lost an average of 1.5 cm over their disease course and had sustained an average of 8 fractures each, whereas fractures were rare in XLH. The XLH cohort had higher incidence of osteotomy (19% versus 0%), spinal stenosis (12% versus 0%), secondary dental abnormalities (95% versus 44%, p < 0.001), and depression and anxiety (46.5% versus 11%). These results deepen our understanding of the subtle differences present between diseases of phosphate wasting. They suggest several biochemical, clinical, and historical features that effectively distinguish TIO from XLH. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

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Section: Discussionmentioning

confidence: 99%

Rare Diseases That Impersonate One Another:X‐LinkedHypophosphatemia andTumor‐InducedOsteomalacia, a Retrospective Analysis of Discriminating Features

et al. 2022

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“…2). (3)(4)(5)(12)(13)(14)(15)18,(20)(21)(22)(23)(24)31,32,(36)(37)(38)(39) There are, however, reports of children with XLH born with features of craniosynostosis. (21,23)…”

Section: Presentation and Diagnosis Of Craniosynostosis In Xlhmentioning

confidence: 99%

Craniosynostosis in Patients With X‐Linked Hypophosphatemia: A Review

Munns

Maguire²,

Williams

et al. 2023

JBMR Plus

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Craniosynostosis is a rare condition of skull development, manifesting during fetal and early infant development, and is usually congenital. Craniosynostosis secondary to metabolic disorders, such as X-linked hypophosphatemia (XLH), is less common and is typically diagnosed later than congenital craniosynostosis. XLH is a rare, progressive, and lifelong hereditary phosphate-wasting disorder characterized by loss of function of the phosphate-regulating endopeptidase homologue, X-linked gene, which is associated with premature fusion of cranial sutures due to abnormal phosphate metabolism (hypophosphatemia) and altered bone mineralization or elevated levels of fibroblast growth factor 23. This targeted literature review of 38 articles seeks to provide an overview of craniosynostosis in individuals with XLH. The objectives of this review are to increase awareness of the prevalence, presentation, and diagnosis of craniosynostosis in XLH; examine the spectrum of craniosynostosis severity in XLH; discuss the management of craniosynostosis in those with XLH; recognize the complications for patients with XLH; and identify what is known about the burden of craniosynostosis for individuals with XLH. The presentation of craniosynostosis in individuals with XLH tends to manifest slightly later than congenital craniosynostosis and can vary in severity and appearance, making diagnosis difficult and resulting in inconsistent clinical outcomes. Consequently, craniosynostosis in patients with XLH is an underreported and potentially underrecognized condition. There have been no studies investigating the effects of craniosynostosis on the quality of life of people with XLH. Despite a growing awareness among researchers and experienced clinicians, there are still improvements to be made in general awareness and timely diagnosis of craniosynostosis in XLH. The XLH community would benefit from further study into the prevalence of craniosynostosis, the effect of XLH medical therapy on the development of craniosynostosis, and the effects of craniosynostosis on quality of life.

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“…The exact mechanism of development is still unclear; it is assumed that the mutated gene contains the building instructions for a membrane protein that regulates the recovery of phosphate in the kidney via fibroblast growth factor (FGF)23 [ 9 ]. The mutation is based on the PHEX gene, where disturbed PHEX protein will be expressed [ 7 ].…”

Section: To the Editormentioning

confidence: 99%

“…As a result of the mutation on the PHEX gene, FGF23 overactivity impairs this recovery [ 1 , 4 , 8 , 9 , 21 ]. FGF23 derives from the FGF19 subfamily [ 4 , 7 ]. In the kidney, a klotho-FGFR1-FGF23 trimeric complex will be built with activation of the mitogen-activated protein kinase (MAPK) pathways [ 9 ].…”

Section: To the Editormentioning

confidence: 99%

“…In the kidney, a klotho-FGFR1-FGF23 trimeric complex will be built with activation of the mitogen-activated protein kinase (MAPK) pathways [9]. Moreover, a downregulation of type IIa and c sodium transporters in the proximal tubulus of the kidney is present [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. As a result, phosphate excretion in the kidney is elevated .…”

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