Review Question - QID 218540

This patient has a mutation in the PHEX gene, which is pathognomonic of X-linked hypophosphatemic rickets (XLH). Medical treatment must be initiated early in life to minimize the expected shortened stature, genu varum, and need for corrective osteotomies.

XLH is the most common form of heritable rickets. The PHEX mutation results in increased production of fibroblast growth factor 23 (FGFR 23) which, at the level of the kidneys, results in stunted phosphate reabsorption and impaired 1,25-OH Vitamin D production. This results in the characteristic low phosphate levels in patients with the disease. However, 1,25-OH Vitamin D levels remain inconspicuously normal or mildly low. Serum calcium remains normal with parathyroid hormone (PTH) reflectively normal as well. Medical management in these pediatric patients includes finding a balance of phosphate and Vitamin D supplementation.

Sharkey and colleagues comprehensively reviewed the medical and surgical treatment for X-linked hypophosphatemic rickets. They discuss early initiation of phosphate and Vitamin D supplements to prevent long-term complications of the disease. They conclude that despite appropriate treatment, some patients progress to requiring corrective osteotomy procedures.

Pettifor performed an exhaustive review of the different forms of rickets and the pathogenesis for each subtype. They stress that current medical management only partially treats each subtype of disease, which may explain why some patients have persistent symptoms despite appropriate management. They conclude that continued research and improvement in the understanding of rickets will open doors to new treatment options in the future.

Figure A shows bilateral knee AP radiographic images of a patient with XLH. The distal femur and proximal tibial physes are vertically widened, which is characteristic of rickets.

Incorrect Answers:
Answer 1: Calcium supplementation alone will not improve the child’s genu varum. XLH is a disease of phosphate wasting and the cornerstone of treatment includes additional phosphate supplementation. Phosphate is taken multiple times per day to maintain adequate levels for continued boney growth.
Answer 3: It is strongly recommended that medical treatment continues in adulthood to prevent bone pains, insufficiency fractures, and poor bone healing.
Answer 4: Appropriate medical management has been shown to improve or completely alleviate the tibial bowing in many patients.
Answer 5: The most common form of inherited rickets is X-linked dominant.