While PHEX gene mutation is the most common form of inherited rickets, limited data exist regarding genetic etiology of hypophosphatemic rickets in Turkey. The aim of this study was to investigate the type of genetic defect in 16 index children and their families (12 unrelated, 1 related).
Following clinical and laboratory assessment, PHEX analysis was made initially unless a mutation in another gene was suspected. If negative, FGF23, SLC34A3, SLC34A1, CYP27B1, VDR, DMP1, and ENPP1 genes were analyzed sequentially.
Following the investigation of index cases and their families, we identified 21 patients (16 children, 5 adults) diagnosed with hypophosphatemic rickets from 13 families. Nineteen of them (91%) had findings related with rickets and 12 (56%) had short stature. Calcium levels were normal, phosphorus low, ALP markedly elevated, and parathormone normal (n=8, 38.1%) or mildly elevated (n=13, 61.9%) in all patients. We found 10 different PHEX mutations in 17 (80.9%) patients, one novel SLC34A3 mutation in two siblings (9.5%), and no mutation in 2 patients (9.5%). Five PHEX mutations were de novo. Four novel PHEX mutations were: c.978_982dupCTACC (frameshift), c.1586+2T>G (splice site), c.436+1G>T (splice site), and c.1217G>T (p.C406F). Affected parents were all symptomatic but none were diagnosed previously.
The present study revealed that PHEX mutation seems to be the most prevalent mutation in Turkey as well. More attention should be paid to hypophosphatemia by the clinicians since some cases remain undiagnosed both during childhood and adulthood.