open access

Vol 72, No 2 (2021)
Original paper
Published online: 2020-12-09
Submitted: 2020-08-28
Accepted: 2020-10-31
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X-linked hypophosphataemic rickets in children: clinical phenotype, therapeutic strategies, and molecular background

Monika Obara-Moszynska, Aleksandra Rojek, Zofia Kolesinska, Dorota Jurkiewicz, Krystyna H. Chrzanowska, Marek Niedziela
DOI: 10.5603/EP.a2020.0087
·
Pubmed: 33295632
·
Endokrynologia Polska 2021;72(2):108-119.

open access

Vol 72, No 2 (2021)
Original Paper
Published online: 2020-12-09
Submitted: 2020-08-28
Accepted: 2020-10-31

Abstract

Introduction: X-linked hypophosphataemic rickets (XLHR) is the most common form of hypophosphataemic rickets (HR), which is caused by mutations in the PHEX gene. The aim of this work was to investigate the clinical phenotype, therapeutic strategies, and molecular background of HR in children hospitalised in our clinic.

Material and methods: Eleven patients aged 5.7–18.25 years were included in this study. Molecular analysis was performed using polymerase chain reaction (PCR) and direct sequencing. The PHEX gene was examined in all of the patients, whereas the FGF23 gene was analysed in 5 patients. All of them were treated with alphacalcidol and phosphorus, and 3 were additionally treated with recombinant human growth hormone (rhGH).

Results: The mean age at HR diagnosis was 4.05 ± 3.35 years. The mean htSDS was –2.99 ± 1.19. In 2 of the 3 patients treated with rhGH the height gain was +0.4SD and +0.3SD, respectively. In 10 of 11 patients, PHEX gene mutations were found. In 2 children, novel mutations in the PHEX gene were identified: c.325_326dupCA, N110Ifs*7 in one patient and c.899_900delTG, M300Kfs*4 in the remaining one, which coexisted with a known polymorphism c.1769-10C > T, rs3752433. In one patient, a novel deletion of exon 14 and 2 polymorphisms were detected: c.1646-46T > C, g.180417T > C, rs3213493 in intron 15 (known) and g.189156C > T in intron 17 (novel).

Conclusion: We report 3 novel mutations in the PHEX responsible for HR. Additionally, this study reports the effects of rhGH therapy for growth promotion in HR.

Abstract

Introduction: X-linked hypophosphataemic rickets (XLHR) is the most common form of hypophosphataemic rickets (HR), which is caused by mutations in the PHEX gene. The aim of this work was to investigate the clinical phenotype, therapeutic strategies, and molecular background of HR in children hospitalised in our clinic.

Material and methods: Eleven patients aged 5.7–18.25 years were included in this study. Molecular analysis was performed using polymerase chain reaction (PCR) and direct sequencing. The PHEX gene was examined in all of the patients, whereas the FGF23 gene was analysed in 5 patients. All of them were treated with alphacalcidol and phosphorus, and 3 were additionally treated with recombinant human growth hormone (rhGH).

Results: The mean age at HR diagnosis was 4.05 ± 3.35 years. The mean htSDS was –2.99 ± 1.19. In 2 of the 3 patients treated with rhGH the height gain was +0.4SD and +0.3SD, respectively. In 10 of 11 patients, PHEX gene mutations were found. In 2 children, novel mutations in the PHEX gene were identified: c.325_326dupCA, N110Ifs*7 in one patient and c.899_900delTG, M300Kfs*4 in the remaining one, which coexisted with a known polymorphism c.1769-10C > T, rs3752433. In one patient, a novel deletion of exon 14 and 2 polymorphisms were detected: c.1646-46T > C, g.180417T > C, rs3213493 in intron 15 (known) and g.189156C > T in intron 17 (novel).

Conclusion: We report 3 novel mutations in the PHEX responsible for HR. Additionally, this study reports the effects of rhGH therapy for growth promotion in HR.

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Keywords

hypophosphataemic rickets; hypophosphataemia; PHEX gene; recombinant human growth hormone therapy; rhGH

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Title

X-linked hypophosphataemic rickets in children: clinical phenotype, therapeutic strategies, and molecular background

Journal

Endokrynologia Polska

Issue

Vol 72, No 2 (2021)

Article type

Original paper

Pages

108-119

Published online

2020-12-09

DOI

10.5603/EP.a2020.0087

Pubmed

33295632

Bibliographic record

Endokrynologia Polska 2021;72(2):108-119.

Keywords

hypophosphataemic rickets
hypophosphataemia
PHEX gene
recombinant human growth hormone therapy
rhGH

Authors

Monika Obara-Moszynska
Aleksandra Rojek
Zofia Kolesinska
Dorota Jurkiewicz
Krystyna H. Chrzanowska
Marek Niedziela

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