Autosomal Dominant Hypophosphatemic Rickets
Autosomal dominant hypophosphatemic rickets (ADHR) displays incomplete penetrance and variable age of onset.
Based on the age of presentation, two subgroups of ADHR are described. One subgroup presents during childhood and mimics X-linked hypophosphatemic rickets.
The other subgroup presents during adolescence or adulthood with bone pain, weakness, and pseudofractures, but no deformity
The gene locus for autosomal dominant hypophosphatemic rickets has been located on chromosome 12p13.
FGF23 is mutated at the cleavage site, leading to impaired cleavage of the intact molecule, thereby prolonging its activity and phosphaturia.
Patients with the early-onset disease have phosphate wasting, rickets, and lower extremity deformities in childhood; but may lose the phosphate-wasting defect after puberty.
Those who present after growth; plate closure have bone pain and fractures, but no deformities. Many females present after pregnancy. Pseudofractures are common.
Serum calcium – Normal
Serum phosphate – Severely decreased
Serum alkaline phosphatase – Increased
Parathyroid hormone assay – Normal or slightly elevated PTH
25(OH) vitamin D – Normal
1,25(OH)2 vitamin D – Low or inappropriately normal
TMP/GFR – Decreased
FGF23 – Increased
Treatment is similar to that of X-linked hypophosphatemic rickets.