Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR): clinical heterogeneity and long-term efficacious management of eight patients from four unrelated Arab families with a loss of function VDR mutation

<h3>Background</h3><p dir="ltr">Vitamin D regulates the concentrations of calcium and phosphate in blood and promotes the growth and remodeling of bones. The circulating active form of vitamin D, 1,25-dihydroxyvitamin D, binds to the vitamin D receptor (VDR), which hetero...

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Main Author: Muhammad Faiyaz-Ul-Haque (14585556) (author)
Other Authors: Waheeb AlDhalaan (14585557) (author), Abdullah AlAshwal (14585558) (author), Bassam S. Bin-Abbas (14585560) (author), Afaf Alsagheir (8987390) (author), Maram AlOtaiby (564512) (author), Zulqurnain Rafiq (14585562) (author), Syed H.E. Zaidi (14585563) (author)
Published: 2018
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author Muhammad Faiyaz-Ul-Haque (14585556)
author2 Waheeb AlDhalaan (14585557)
Abdullah AlAshwal (14585558)
Bassam S. Bin-Abbas (14585560)
Afaf Alsagheir (8987390)
Maram AlOtaiby (564512)
Zulqurnain Rafiq (14585562)
Syed H.E. Zaidi (14585563)
author2_role author
author
author
author
author
author
author
author_facet Muhammad Faiyaz-Ul-Haque (14585556)
Waheeb AlDhalaan (14585557)
Abdullah AlAshwal (14585558)
Bassam S. Bin-Abbas (14585560)
Afaf Alsagheir (8987390)
Maram AlOtaiby (564512)
Zulqurnain Rafiq (14585562)
Syed H.E. Zaidi (14585563)
author_role author
dc.creator.none.fl_str_mv Muhammad Faiyaz-Ul-Haque (14585556)
Waheeb AlDhalaan (14585557)
Abdullah AlAshwal (14585558)
Bassam S. Bin-Abbas (14585560)
Afaf Alsagheir (8987390)
Maram AlOtaiby (564512)
Zulqurnain Rafiq (14585562)
Syed H.E. Zaidi (14585563)
dc.date.none.fl_str_mv 2018-06-27T00:00:00Z
dc.identifier.none.fl_str_mv 10.1515/jpem-2017-0312
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Hereditary_1_25-dihydroxyvitamin_D-resistant_rickets_HVDRR_clinical_heterogeneity_and_long-term_efficacious_management_of_eight_patients_from_four_unrelated_Arab_families_with_a_loss_of_function_VDR_mutation/22046924
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biomedical and clinical sciences
Clinical sciences
Paediatrics
alopecia
growth retardation
hereditary 1,25-dihydroxyvitamin D-resistant rickets
treatment
vitamin D receptor mutation
dc.title.none.fl_str_mv Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR): clinical heterogeneity and long-term efficacious management of eight patients from four unrelated Arab families with a loss of function VDR mutation
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <h3>Background</h3><p dir="ltr">Vitamin D regulates the concentrations of calcium and phosphate in blood and promotes the growth and remodeling of bones. The circulating active form of vitamin D, 1,25-dihydroxyvitamin D, binds to the vitamin D receptor (VDR), which heterodimerizes with the retinoid X receptor to regulate the expression of target genes. Inactivating mutations in the <i>VDR</i> gene cause hereditary vitamin D-resistant rickets (HVDRR), a rare disorder characterized by an early onset of rickets, growth retardation, skeletal deformities, hypocalcemia, hypophosphatemia and secondary hyperparathyroidism, and in some cases alopecia.</p><h3>Methods</h3><p dir="ltr">We describe eight new HVDRR patients from four unrelated consanguineous families. The <i>VDR</i> gene was sequenced to identify mutations. The management of patients over a period of up to 11 years following the initial diagnosis is assessed.</p><h3>Results</h3><p dir="ltr">Although all patients exhibit main features of HVDRR and carry the same c.885C>A (p.Y295*) loss of function mutation in the <i>VDR</i> gene, there was heterogeneity of the manifestations of HVDRR-associated phenotypes and developmental milestones. These eight patients were successfully treated over a period of 11 years. All clinical symptoms were improved except alopecia.</p><h3>Conclusions</h3><p dir="ltr">The study concludes that <i>VDR</i> sequencing and laboratory tests are essential to confirm HVDRR and to assess the effectiveness of the treatment.</p><h2>Other information</h2><p dir="ltr">Published in: Journal of Pediatric Endocrinology and Metabolism<br>License: <a href="http://creativecommons.org/licenses/by/4.0" target="_blank">http://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1515/jpem-2017-0312" target="_blank">http://dx.doi.org/10.1515/jpem-2017-0312</a></p>
eu_rights_str_mv openAccess
id Manara2_ed6c680c2c0b95281cf8fc7e454ca889
identifier_str_mv 10.1515/jpem-2017-0312
network_acronym_str Manara2
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oai_identifier_str oai:figshare.com:article/22046924
publishDate 2018
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rights_invalid_str_mv CC BY 4.0
spelling Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR): clinical heterogeneity and long-term efficacious management of eight patients from four unrelated Arab families with a loss of function VDR mutationMuhammad Faiyaz-Ul-Haque (14585556)Waheeb AlDhalaan (14585557)Abdullah AlAshwal (14585558)Bassam S. Bin-Abbas (14585560)Afaf Alsagheir (8987390)Maram AlOtaiby (564512)Zulqurnain Rafiq (14585562)Syed H.E. Zaidi (14585563)Biomedical and clinical sciencesClinical sciencesPaediatricsalopeciagrowth retardationhereditary 1,25-dihydroxyvitamin D-resistant ricketstreatmentvitamin D receptor mutation<h3>Background</h3><p dir="ltr">Vitamin D regulates the concentrations of calcium and phosphate in blood and promotes the growth and remodeling of bones. The circulating active form of vitamin D, 1,25-dihydroxyvitamin D, binds to the vitamin D receptor (VDR), which heterodimerizes with the retinoid X receptor to regulate the expression of target genes. Inactivating mutations in the <i>VDR</i> gene cause hereditary vitamin D-resistant rickets (HVDRR), a rare disorder characterized by an early onset of rickets, growth retardation, skeletal deformities, hypocalcemia, hypophosphatemia and secondary hyperparathyroidism, and in some cases alopecia.</p><h3>Methods</h3><p dir="ltr">We describe eight new HVDRR patients from four unrelated consanguineous families. The <i>VDR</i> gene was sequenced to identify mutations. The management of patients over a period of up to 11 years following the initial diagnosis is assessed.</p><h3>Results</h3><p dir="ltr">Although all patients exhibit main features of HVDRR and carry the same c.885C>A (p.Y295*) loss of function mutation in the <i>VDR</i> gene, there was heterogeneity of the manifestations of HVDRR-associated phenotypes and developmental milestones. These eight patients were successfully treated over a period of 11 years. All clinical symptoms were improved except alopecia.</p><h3>Conclusions</h3><p dir="ltr">The study concludes that <i>VDR</i> sequencing and laboratory tests are essential to confirm HVDRR and to assess the effectiveness of the treatment.</p><h2>Other information</h2><p dir="ltr">Published in: Journal of Pediatric Endocrinology and Metabolism<br>License: <a href="http://creativecommons.org/licenses/by/4.0" target="_blank">http://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1515/jpem-2017-0312" target="_blank">http://dx.doi.org/10.1515/jpem-2017-0312</a></p>2018-06-27T00:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1515/jpem-2017-0312https://figshare.com/articles/journal_contribution/Hereditary_1_25-dihydroxyvitamin_D-resistant_rickets_HVDRR_clinical_heterogeneity_and_long-term_efficacious_management_of_eight_patients_from_four_unrelated_Arab_families_with_a_loss_of_function_VDR_mutation/22046924CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/220469242018-06-27T00:00:00Z
spellingShingle Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR): clinical heterogeneity and long-term efficacious management of eight patients from four unrelated Arab families with a loss of function VDR mutation
Muhammad Faiyaz-Ul-Haque (14585556)
Biomedical and clinical sciences
Clinical sciences
Paediatrics
alopecia
growth retardation
hereditary 1,25-dihydroxyvitamin D-resistant rickets
treatment
vitamin D receptor mutation
status_str publishedVersion
title Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR): clinical heterogeneity and long-term efficacious management of eight patients from four unrelated Arab families with a loss of function VDR mutation
title_full Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR): clinical heterogeneity and long-term efficacious management of eight patients from four unrelated Arab families with a loss of function VDR mutation
title_fullStr Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR): clinical heterogeneity and long-term efficacious management of eight patients from four unrelated Arab families with a loss of function VDR mutation
title_full_unstemmed Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR): clinical heterogeneity and long-term efficacious management of eight patients from four unrelated Arab families with a loss of function VDR mutation
title_short Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR): clinical heterogeneity and long-term efficacious management of eight patients from four unrelated Arab families with a loss of function VDR mutation
title_sort Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR): clinical heterogeneity and long-term efficacious management of eight patients from four unrelated Arab families with a loss of function VDR mutation
topic Biomedical and clinical sciences
Clinical sciences
Paediatrics
alopecia
growth retardation
hereditary 1,25-dihydroxyvitamin D-resistant rickets
treatment
vitamin D receptor mutation