Abstract
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.
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Data collection and analysis were performed by SRN. The first draft of the manuscript was written by SRN and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Simone Rask Nielsen, Stinus Gadegaard Hansen, Claus Bistrup, Klaus Brusgaard and Anja Lisbeth Frederiksen have no relevant financial or non-financial interests to disclose.
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Nielsen, S.R., Hansen, S.G., Bistrup, C. et al. Bone Deformities and Kidney Failure: Coincidence of PHEX-Related Hypophosphatemic Rickets and m.3243A>G Mitochondrial Disease. Calcif Tissue Int 111, 641–645 (2022). https://doi.org/10.1007/s00223-022-01010-x
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DOI: https://doi.org/10.1007/s00223-022-01010-x