Bone Deformities and Kidney Failure: Coincidence of PHEX-Related Hypophosphatemic Rickets and m.3243A>G Mitochondrial Disease

Simone Rask Nielsen*, Stinus Gadegaard Hansen, Claus Bistrup, Klaus Brusgaard, Anja Lisbeth Frederiksen

*Corresponding author for this work

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X-linked hypophosphatemic rickets (XLH) and m.3243A>G mitochondrial disease share several clinical findings, including short stature, hearing impairment (HI), nephropathy, and hypertension. Here, we report on a case with the rare coincidence of these two genetic conditions. In early childhood, the patient presented with hypophosphatemia and bone deformities and was clinically diagnosed with XLH. This was genetically verified in adulthood with the identification of a de novo pathogenic deletion in phosphate-regulating endopeptidase homolog X-linked (PHEX). In addition, the patient developed HI and hypertension and when his mother was diagnosed with m.3243A>G, subsequent genetic testing confirmed the patient to carry the same variant. Over the next two decades, the patient developed progressive renal impairment however without nephrocalcinosis known to associate with XLH which could indicate an m.3243A>G-related kidney disease. Parallel with the progression of renal impairment, the patient developed hyperphosphatemia and secondary hyperparathyroidism. In conclusion, this case represents a complex clinical phenotype with the reversal of hypo- to hyperphosphatemia in XLH potentially mediated by the development of an m.3243A>G-associated nephropathy.

Original languageEnglish
JournalCalcified Tissue International
Issue number6
Pages (from-to)641-645
Publication statusPublished - Dec 2022

Bibliographical note

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.


  • Bone deformities
  • Hypophosphatemic rickets
  • Kidney disease
  • m.3243A>G
  • PHEX
  • Familial Hypophosphatemic Rickets/complications
  • Humans
  • Child, Preschool
  • Hyperphosphatemia/complications
  • Hypertension/complications
  • PHEX Phosphate Regulating Neutral Endopeptidase/genetics
  • Mitochondrial Diseases/complications
  • Renal Insufficiency/complications
  • Rickets, Hypophosphatemic
  • Genetic Diseases, X-Linked/complications
  • Mutation


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