X-Linked Hypophosphatemia Management in Children: An International Working Group Clinical Practice Guideline - Report - MDSpire

X-Linked Hypophosphatemia Management in Children: An International Working Group Clinical Practice Guideline

  • By

  • Dalal S Ali

  • Thomas O Carpenter

  • Erik A Imel

  • Leanne M Ward

  • Natasha M Appelman-Dijkstra

  • Catherine Chaussain

  • Suzanne M Jan de Beur

  • Pablo Florenzano

  • Hajar Abu Alrob

  • Rana Aldabagh

  • R Todd Alexander

  • Farah Alsarraf

  • Signe Sparre Beck-Nielsen

  • Martin Biosse-Duplan

  • Rachel K Crowley

  • Karel Dandurand

  • Guido Filler

  • Lisa Friedlander

  • Seiji Fukumoto

  • Claudia Gagnon

  • Paul Goodyer

  • Corinna Grasemann

  • Chelsey Grimbly

  • Salma Hussein

  • Muhammad K Javaid

  • Sarah Khan

  • Aneal Khan

  • Anna Lehman

  • Willem F Lems

  • E Michael Lewiecki

  • Ciara McDonnell

  • Reza D Mirza

  • Emmett Morgante

  • Archibald Morrison

  • Anthony A Portale

  • Christina Rao

  • Yumie Rhee

  • Eric T Rush

  • Heide Siggelkow

  • Sotirios Tetradis

  • Laura Tosi

  • Gordon Guyatt

  • Maria Luisa Brandi

  • Aliya A Khan

  • February 17, 2025

  • 0 min

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Clinical Practice Guidelines for Pediatric X-Linked Hypophosphatemia Management

Overview

An International Working Group developed updated clinical practice guidelines for diagnosing, evaluating, managing, and monitoring X-linked hypophosphatemia (XLH) in children. These guidelines incorporate systematic reviews, expert consensus, and GRADE methodology to provide evidence-based recommendations on treatment strategies, diagnosis, and monitoring.

Background

X-linked hypophosphatemia (XLH) is a rare inherited disorder caused by pathogenic variants in the PHEX gene, leading to increased FGF23 and chronic hypophosphatemia due to renal phosphate wasting. This results in impaired bone mineralization, skeletal deformities, and dental complications in children. While adults may develop enthesopathy and arthritis, pediatric manifestations primarily involve bone and dental abnormalities. Advances in understanding XLH over the past five years have informed these comprehensive guidelines.

Data Highlights

The guidelines are based on two systematic reviews comparing burosumab versus conventional therapy or no therapy, and conventional therapy versus no therapy, assessing patient-important outcomes. The quality of evidence was evaluated using GRADE methodology. Monitoring recommendations were derived from an expert clinical practice survey with at least 80% consensus among 50 international experts. Treatment recommendations were classified as strong or weak based on evidence certainty.

Key Findings

  • Diagnosis of XLH in children is based on chronic hypophosphatemia with exclusion of other causes of renal phosphate wasting and supported by an X-linked inheritance pattern.
  • Characteristic clinical features include lower limb deformities, craniosynostosis-related dolichocephaly, recurrent dental abscesses, growth delay, muscle weakness, delayed motor milestones, bone pain, and fractures.
  • Burosumab treatment shows benefits compared to conventional therapy or no therapy, with recommendations graded using GRADE methodology.
  • Monitoring recommendations are based on expert consensus with very low certainty of evidence, emphasizing the need for multidisciplinary follow-up.
  • Dental complications are common and specific strategies to mitigate these are proposed in the guidelines.
  • Expert consensus and patient values were incorporated into recommendations, with strong recommendations phrased as "we recommend" and weaker ones as "we suggest."

Clinical Implications

Clinicians should consider chronic hypophosphatemia and family history when diagnosing XLH in children and utilize a multidisciplinary approach for management. Burosumab is recommended as a treatment option based on current evidence, while monitoring should be individualized according to expert consensus. Attention to dental health and early intervention for skeletal deformities are important components of care.

Conclusion

These updated clinical practice guidelines provide comprehensive, evidence-based recommendations for the diagnosis, treatment, and monitoring of XLH in pediatric patients, supporting improved multidisciplinary care and patient outcomes.

References

  1. International Working Group on XLH, 2024 -- Clinical Practice Guidelines for the Management of X-Linked Hypophosphatemia in Pediatric Patients

Original Source(s)

X-Linked Hypophosphatemia Management in Children: An International Working Group Clinical Practice Guideline

  • by Dalal S Ali, Thomas O Carpenter, Erik A Imel, Leanne M Ward, Natasha M Appelman-Dijkstra, Catherine Chaussain, Suzanne M Jan de Beur, Pablo Florenzano, Hajar Abu Alrob, Rana Aldabagh, R Todd Alexander, Farah Alsarraf, Signe Sparre Beck-Nielsen, Martin Biosse-Duplan, Rachel K Crowley, Karel Dandurand, Guido Filler, Lisa Friedlander, Seiji Fukumoto, Claudia Gagnon, Paul Goodyer, Corinna Grasemann, Chelsey Grimbly, Salma Hussein, Muhammad K Javaid, Sarah Khan, Aneal Khan, Anna Lehman, Willem F Lems, E Michael Lewiecki, Ciara McDonnell, Reza D Mirza, Emmett Morgante, Archibald Morrison, Anthony A Portale, Christina Rao, Yumie Rhee, Eric T Rush, Heide Siggelkow, Sotirios Tetradis, Laura Tosi, Gordon Guyatt, Maria Luisa Brandi, Aliya A Khan

  • February 17, 2025

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