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Rare PHEX variant with insidious presentation leads to a delayed diagnosis of X-linked hypophosphatemia
  1. Cathrine Constantacos1,
  2. Janel Darcy Hunter1,
  3. Elizabeth Tharpe Walsh1 and
  4. Andrew Michael South2,3
  1. 1Pediatrics, Section of Endocrinology, Wake Forest University School of Medicine, Winston Salem, North Carolina, USA
  2. 2Pediatrics, Section of Nephrology, Wake Forest University School of Medicine, Winston Salem, North Carolina, USA
  3. 3Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston Salem, North Carolina, USA
  1. Correspondence to Dr Cathrine Constantacos; caconsta{at}


A 7-year-old girl without a significant previous medical history was diagnosed with X-linked hypophosphatemic rickets (XLHR) due to a rare, most likely pathogenic, PHEX gene variant after a 4-year delayed diagnosis due to mild clinical presentation. At 2 years of age, her intoeing and femoral bowing were attributed to physiologic bowing and borderline vitamin D sufficiency, despite phosphorus not being measured. Hypophosphatemia was eventually detected after incomplete improvement of bowing and leg length discrepancy with suboptimal linear growth. This rare PHEX variant (c.1949T>C, p.Leu650Pro) further supported the clinical diagnosis of XLHR. Treatment with burosumab (an anti-FGF23 monoclonal antibody) normalised phosphorus and alkaline phosphatase levels and improved her bowing. The diverse phenotypic presentation of this variant can result in delayed diagnosis and highlights the importance of prompt assessment of phosphorus levels in patients with skeletal deformities to ensure timely recognition and treatment.

  • paediatrics
  • congenital disorders
  • genetics
  • calcium and bone

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  • Contributors All authors are equally responsible for the authorship of the submitted case and drafted and critically revised the manuscript and approved the submitted version. Each author’s contribution was invaluable to the final version. CC was involved directly in the patient’s case, conceived and researched the case and wrote the paper. JDH significantly contributed to the collection of data and editing of the write-up of the paper. ETW significantly contributed to the data collection and editing of the write up of the paper. AMS was involved directly in the patient’s case and contributed significantly to the write-up of the case as it pertains to the renal system as well as to the editing of the write-up.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests AMS reports three grants from NIH NHLBI for XLH research. CC has nothing to disclose. JDH has nothing to disclose. ETW has nothing to disclose.

  • Provenance and peer review Not commissioned; externally peer reviewed.