Startseite Rare PHEX intron variant causes complete and severe phenotype in a family with hypophosphatemic rickets: a case report
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Rare PHEX intron variant causes complete and severe phenotype in a family with hypophosphatemic rickets: a case report

  • Francesca Aiello ORCID logo EMAIL logo , Daniela Pasquali , Federico Baronio , Alessandra Cassio , Cesare Rossi , Rosa Di Fraia , Raffaela Carotenuto , Lucia Digitale , Adalgisa Festa , Caterina Luongo , Giulio Maltoni , Roberta Schiano di Cola , Emanuele Miraglia Del Giudice und Anna Grandone
Veröffentlicht/Copyright: 10. November 2022
Journal of Pediatric Endocrinology and Metabolism
Aus der Zeitschrift Journal of Pediatric Endocrinology and Metabolism Band 36 Heft 1

Abstract

Objectives

Lower limb deformities in children need careful orthopedic evaluation to distinguish physiological forms from pathological ones. X-linked hypophosphatemia (XLH) is a rare hereditary condition caused by PHEX gene mutations where tibial varum can be the first sign.

Case presentation

We report a family presenting with severe tibial varum, harbouring a rare PHEX intron mutation, c.1586+6T>C. This is the first clinical description available in literature for this variant. Despite the previous prediction of a mild phenotype in functional study, our patients showed important bone deformities, rickets and impaired growth since infancy followed by severe bone pain, hearing loss and reduced life quality in adulthood. Burosumab therapy improved biochemical and radiological findings in children and ameliorated quality of life in adults.

Conclusions

This case demonstrated c.1586+6T>C causes a severe XLH phenotype, responsive to Burosumab. Familial genetic screening, enlarged to intronic region analysis, when XLH is suspected, allows precocious diagnosis to start timely the appropriate treatment.

Keywords: hereditary hypophosphatemic rickets; PHEX intron variants; XLH mutational analysis
Corresponding author: Francesca Aiello, Department of Child, Woman, General and Specialized Surgery, Università degli Studi della Campania “L. Vanvitelli”, Vico Luigi De Crecchio, 2 Naples, IT-80138, Italy, Phone: +39-0815665461, E-mail:

Acknowledgments

We thank our patients for their will to contribute to the medical and scientific progress by sharing their story.

  1. Research funding: None declared.

  2. Author contributions: AF wrote the main draft and performs literature review. RSDC described pediatric patient case and retrieved clinical data. FB, GM, CL and AF clinically managed hypophosphatemic rickets in pediatric patients. CR performed genetic analysis. RDF, RC, LD managed adult patient and described the adult phenothype in the original draft. DP, AC and AG conceptualized the idea of the manuscript and supervised the work. EMG revised the draft manuscript. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: Not applicable.

References

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Received: 2022-07-30
Accepted: 2022-10-17
Published Online: 2022-11-10
Published in Print: 2023-01-27

© 2022 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Disorders of sex development – biologic, genetic, cultural, societal, and psychologic diversity of the human nature
  4. Review
  5. Diagnostic approach in 46, XY DSD: an endocrine society of bengal (ESB) consensus statement
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  8. Evaluation of bladder dysfunction in children and adolescents with type 1 diabetes mellitus by uroflowmetry
  9. All aspects of galactosemia: a single center experience
  10. The evolution of pituitary cysts in growth hormone-treated children
  11. Phototherapy-induced hypocalcemia and hypoparathyroidism in icteric term newborns
  12. Clinical and laboratory evaluation of children with congenital hyperinsulinism: a single center experience
  13. Does cystatin C have an immunomodulatory role in Hashimoto’s thyroiditis?
  14. Molecular genetic etiology by whole exome sequence analysis in cases with familial type 1 diabetes mellitus without HLA haplotype predisposition or incomplete predisposition
  15. Features of BSCL2 related congenital generalized lipodystrophy in China: long-term follow-up of three patients and literature review
  16. Case Reports
  17. Congenital adrenal hyperplasia with a CYP21A2 deletion overlapping the tenascin-X gene: an atypical presentation
  18. The smallest dislocated microduplication of Xq27.1 harboring SOX3 gene associated with XX male phenotype
  19. Rare PHEX intron variant causes complete and severe phenotype in a family with hypophosphatemic rickets: a case report
  20. Human chorionic gonadotrophin secreting adrenocortical neoplasm presenting with peripheral precocious puberty in an infant
  21. Atypical familial diabetes associated with a novel NEUROD1 nonsense variant
https://doi.org/10.1515/jpem-2022-0365
Schlagwörter für diesen Artikel
hereditary hypophosphatemic rickets; PHEX intron variants; XLH mutational analysis

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Disorders of sex development – biologic, genetic, cultural, societal, and psychologic diversity of the human nature
  4. Review
  5. Diagnostic approach in 46, XY DSD: an endocrine society of bengal (ESB) consensus statement
  6. Original Articles
  7. Penile diameter during puberty in boys: a retrospective analysis of longitudinally obtained data
  8. Evaluation of bladder dysfunction in children and adolescents with type 1 diabetes mellitus by uroflowmetry
  9. All aspects of galactosemia: a single center experience
  10. The evolution of pituitary cysts in growth hormone-treated children
  11. Phototherapy-induced hypocalcemia and hypoparathyroidism in icteric term newborns
  12. Clinical and laboratory evaluation of children with congenital hyperinsulinism: a single center experience
  13. Does cystatin C have an immunomodulatory role in Hashimoto’s thyroiditis?
  14. Molecular genetic etiology by whole exome sequence analysis in cases with familial type 1 diabetes mellitus without HLA haplotype predisposition or incomplete predisposition
  15. Features of BSCL2 related congenital generalized lipodystrophy in China: long-term follow-up of three patients and literature review
  16. Case Reports
  17. Congenital adrenal hyperplasia with a CYP21A2 deletion overlapping the tenascin-X gene: an atypical presentation
  18. The smallest dislocated microduplication of Xq27.1 harboring SOX3 gene associated with XX male phenotype
  19. Rare PHEX intron variant causes complete and severe phenotype in a family with hypophosphatemic rickets: a case report
  20. Human chorionic gonadotrophin secreting adrenocortical neoplasm presenting with peripheral precocious puberty in an infant
  21. Atypical familial diabetes associated with a novel NEUROD1 nonsense variant
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