This patient's radiograph shows bilateral bowing of the tibia and femur, suggesting inadequate bone mineralization due to metabolic disease. His lab values are consistent with Vitamin D-Resistant Rickets (aka Familial Hypophospatemic Rickets).
Familial Hypophosphatemic Rickets is the most common form of rickets. It is often caused by an x-linked dominant mutation in the PHEX gene, leading to an inability of the renal tubules to absorb phosphate (GFR remains normal). This leads to inadequate mineralization of bone and commonly presents as bilateral tibial bowing between the ages of 6 months and 2 years. Key lab values for the diagnosis are low serum phosphorous and elevated alkaline phosphatase. Serum calcium is usually normal or low normal. High dose vitamin D3 and corrective surgery is currently the standard of care for hypophosphatemic rickets. Although phosphate replacement is the intuitive solution, current literature regarding the benefit of phosphate replacement for these patients is controversial.
Nield et al. review the topic of rickets noting that, contrary to popular belief, it is not a disease of the past. The authors stress the importance of a thorough history, physical exam, and correct interpretation of lab values in order to achieve an early diagnosis and prevent severe deformity. Genetic counseling for those with inherited forms of rickets is also recommended.
Baroncelli et al. review the topic of hypophosphatemic rickets and note that an increasing number of cases are related to an autosomal dominant mutation causing activation and overproduction of fibroblast growth factor 23 (FGF23). This form of hypophosphatemic rickets also responds to therapy with vitamin D metabolites and inorganic phosphates, but there is hope that the effects of this mutation could be negated with FGF23 neutralizing antibodies.
Figure A is a photograph of bilateral tibial bowing caused by rickets. Illustration A is a table listing the metabolic derangements associated with a number of disorders affect bone mineralization. Illustration B is an anteroposterior radiograph of the lower extremities of a child with rickets, demonstrating bowing of the femur and tibia bilaterally.
Answer 2: Patients with vitamin D deficient rickets have a nutritional lack of vitamin D and will have decreased serum calcium, phosphorous, and vitamin D, with elevated alkaline phosphatase and PTH.
Answer 3: Patients with type II vitamin D dependent Rickets have an autosomal recessive mutation leading to a defect in the intracellular receptor for 1,25-(OH)2-vitamin D. They will present with decreased serum calcium and phosphorous and have elevated alkaline phosphatase and exceptionally high levels of vitamin D.
Answer 4: Pseudohypoparathryoidism is caused by a defect in the parathyroid receptor, making it unresponsive to PTH. These patients will have decreased serum calcium and vitamin D and elevated phosphorous and PTH.
Answer 5: Renal osteodystrophy is characterized by inability to excrete phosphorous as a result of renal failure. As a result of chronic hyperphosphatemia, patients develop hypocalcemia and have increased levels of alkaline phosphatase and PTH.
Nield LS, Mahajan P, Joshi A, Kamat D. Rickets: not a disease of the past. Am
PMID:16939184 (Link to Abstract)
Baroncelli GI, Toschi B, Bertelloni S. Hypophosphatemic rickets. Curr Opin
PMID:23108197 (Link to Abstract)