Hypophosphatemic rickets (previously called vitamin D–resistant rickets) is a disorder in which the bones become painfully soft and bend easily because the blood contains low levels of phosphate.
This very rare disorder is nearly always hereditary, passed as a dominant gene that is carried on the X chromosome, one of the two sex chromosomes. The genetic defect causes a kidney abnormality that allows an inappropriately high amount of phosphate to be excreted into the urine, resulting in low levels of phosphate in the blood. Because bones need phosphate for growth and strength, this deficiency causes defective bones. Females with hypophosphatemic rickets have less severe bone disease than do males. In rare cases, the disorder develops as a result of certain cancers, such as giant cell tumors of bone, sarcomas, prostate cancer, and breast cancer. Hypophosphatemic rickets is not the same as rickets caused by vitamin D deficiency (see see Vitamin D Deficiency).
Symptoms and Diagnosis
Hypophosphatemic rickets usually begins to cause abnormalities in the first year of life. Abnormalities may be so mild that they cause no noticeable symptoms or so severe that they cause bowing of the legs and other bone deformities, bone pain, and a short stature. Bony outgrowth where muscles attach to bones may limit movement at those joints. The space between a baby's skull bones may close too soon, leading to seizures. Laboratory tests show that calcium levels in the blood are normal but phosphate levels are low.
The aim of treatment is to raise phosphate levels in the blood, which promotes normal bone formation. Phosphate can be taken by mouth and should be combined with calcitriol, the activated form of vitamin D. Taking vitamin D alone is not sufficient. The amounts of phosphate and calcitriol must be adjusted carefully because this treatment often leads to high levels of calcium in the blood, the accumulation of calcium in kidney tissue, or kidney stones. These effects can harm the kidneys and other tissues. In some adults, hypophosphatemic rickets resulting from cancer improves dramatically after the cancer is removed.
Last full review/revision December 2006 by Peter C. Brazy, MD