Autosomal dominant hypophosphatemic rickets (ADHR) is a rare disorder with isolated renal phosphate wasting, hypophosphatemia [below 2.5 mg/dL (0.8 mmol/L)], and improperly normal 1, 25-dihydroxyvitamin D3 (calcitriol) levels. Phosphate is vital for a wide array of cellular functions, e.g., it serves as a buffer serum and urine, stores energy in the phosphate bonds of ATP, and is required for building nucleic acids (DNA and RNA). Around 300 mg of phosphate per day penetrates and departs bone tissue. The clinical features of this condition vary widely and they include bone pain, enthesopathy, osteomalacia, rickets, craniosynostosis, and tooth abscesses. The symptoms commence during early childhood with mild cases comprising only hypophosphatemia, while severe cases manifest in slow growth and smaller height. Children with hypophosphatemic rickets develop bone anomalies that obstruct movement and lead to bone pain. The most visible abnormalities include bowed legs or knock knees which worsen if not treated. ADHR can be cured through increasing phosphate intake and high doses of vitamin D. With treatment, hypophosphatemia can improve with time by partly offsetting urine losses of phosphate. There are different types of hereditary hypophosphatemic rickets other than autosomal dominant including autosomal recessive and X-linked recessive, the most common being X-linked hypophosphatemic rickets (XLH).
Autosomal dominant hypophosphatemic rickets originates due to mutations in the fibroblast growth factor 23 (FGF23) gene.
Throughout the period of 1982 and 1988, Lubani et al. (1990) reported 24 children diagnosed with familial hypophosphatemic rickets (FHR), nine of those were diagnosed during family screening of index patients. The average annual incidence of FHR was calculated at 0.2/1000 live births. The cohort comprised of 16 boys and eight girls in 10 families and of those, nine had more than one affected child, meanwhile the mean age of onset was 6.9 years. The most common features presented in all index and screening patients were growth retardation and bowing of the legs. Treatment with 1-alpha-hydroxyvitamin D3 and phosphates was employed and was found to correlate in all patients with acceleration of growth. Moreover, 21 subjects experienced healing of rickets and 22 children had normalization of the serum phosphate. Lubani et al. (1990) presented that up till publication time, two children with late diagnosis were older than 16 years together with a final height beneath the 3rd centile. Furthermore, three pubertal children experienced a height of less than 3rd centile.
Gibraa et al. (2010) reported the case of a Tunisian family in which one parent and three children showed clinical and biological features of ADHR. Mutation analysis of the FGF23 gene revealed a heterozygous substitution of the C at position 526 by a T (c.526C>T), leading to an amino acid replacement of the FGF23 protein (p.R176W) at position 176, which is located in the consensus sequence for the proteolytic cleavage domain.