Autosomal dominant hypophosphatemic rickets (ADHR; MIM 193100) is a hereditary disorder characterized by isolated renal
phosphate wasting,
hypophosphatemia, and inappropriately normal
1,25-dihydroxyvitamin D(3) levels. Recent studies have shown that the
fibroblast growth factor 23 (FGF23) gene is responsible for this disease. FGF23
protein is a phosphaturic factor that is elevated in several diseases associated with
hypophosphatemia and
rickets but varies with disease status in ADHR. In the present study we observed a Chinese family of Han ethnic origin diagnosed with ADHR. The proband is a 30-year-old woman with no history of
rickets but with multiple tooth
abscesses as a young adult. She presented with progressive painful swelling of the left ankle after a blunt
trauma at 26 years of age. She developed
back pain, generalized weakness, and
fatigue, and she could barely walk at age 27. She was found to have severe
hypophosphatemia, low ratio of
phosphorus tubule maximum (
TmP) to glomerular filtration rate (GFR) (
TmP/GFR), and elevated
alkaline phosphatase at age 28. Her brother, 26 years old, presented with
fatigue at 24 years of age and is normophosphatemic. The parents of this family had no history of
rickets or
hypophosphatemia. Direct sequence analysis of genomic
DNA demonstrated a single heterozygous c.527G>A (p.R176Q) mutation in the FGF23 gene in three family members, including the proband, her brother, and their mother. Intact FGF23 assay of seven time points during the oral
phosphate loading test showed no significant relationship between intact FGF23 and serum
phosphorus levels of the subject with ADHR and a control. It is probably the first report of a Chinese family with ADHR.