TY - JOUR
T1 - Bone Deformities and Kidney Failure
T2 - Coincidence of PHEX-Related Hypophosphatemic Rickets and m.3243A>G Mitochondrial Disease
AU - Nielsen, Simone Rask
AU - Hansen, Stinus Gadegaard
AU - Bistrup, Claus
AU - Brusgaard, Klaus
AU - Frederiksen, Anja Lisbeth
N1 - © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
KW - Bone deformities
KW - Hypophosphatemic rickets
KW - Kidney disease
KW - PHEX
KW - m.3243A>G
UR - http://www.scopus.com/inward/record.url?scp=85135223120&partnerID=8YFLogxK
U2 - 10.1007/s00223-022-01010-x
DO - 10.1007/s00223-022-01010-x
M3 - Journal article
C2 - 35916905
SN - 0171-967X
VL - 111
SP - 641
EP - 645
JO - Calcified Tissue International
JF - Calcified Tissue International
IS - 6
ER -