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

Calcif Tissue Int. 2022 Dec;111(6):641-645. doi: 10.1007/s00223-022-01010-x.

PMID: 35916905

Simone Rask Nielsen, Stinus Gadegaard Hansen, Claus Bistrup

Highlights: This article reports a rare case of coexistence of the two genetic conditions, X-linked hypophosphatemic rickets (XLH) and m.3243A>G mitochondrial disease.

Abstract

Background: The clinical characteristics of m.3243A>G mitochondrial disease and X-linked hypophosphatemic rickets (XLH) include low stature, hearing impairment (HI), nephropathy, and hypertension.

Results: Here, a case is described in which these two genetic disorders occurred in a rare coincidence. The patient had hypophosphatemia and bone abnormalities as a young child and was clinically determined to have XLH. With the discovery of a de novo pathogenic deletion in the phosphate-regulating endopeptidase homolog X-linked gene, this was genetically confirmed in adulthood (PHEX). In addition, the patient experienced HI and hypertension. Genetic testing later revealed that the patient carries the same mutation as his mother, who was found to have m.3243A>G. The patient gradually lost renal function over the course of the next 20 years, although there was no nephrocalcinosis, which is associated with XLH and may be a sign of kidney disease linked to m.3243A>G. The patient's development of secondary hyperparathyroidism and hyperphosphatemia coincided with the advancement of renal impairment.

Conclusion: The development of a m.3243A>G-associated nephropathy may have had a role in the reversal of hypo- to hyperphosphatemia in XLH in this case, which, in turn, represents a complex clinical presentation.

Keywords: Bone deformities, Hypophosphatemic rickets, Kidney disease, PHEX, m.3243A>G