Hypophosphatemic Rickets in Opsismodysplasia

BACKGROUND: Opsismodysplasia is a rare spondylo(epi)chondrodysplasia characteristized by delayed skeletal maturation and a constellation of dysplastic features. Although metaphyseal irregularities/cupping have been noted, neither renal phosphate wasting nor rickets have previously been reported. OBJECTIVE: To evaluate hypophosphatemia and rickets in opsismodysplasia. PATIENTS: Two girls with opsismodysplasia presenting with hypophoshpatemia by 3 years of age. METHODS: Routine biochemistries to assess hypophosphatemia and renal phosphate wasting; radiographs (rachitic changes) and DEXA scan (BMD); FGF23 levels, PHEX and FGF23 gene analyses performed (Patient 1). RESULTS: Both children had hypophosphatemia, decreased TRP, and rickets. Oral phosphorus and calcitriol improved metaphyseal mineralization, yet serum phosphate levels remained relatively low and renal phosphate wasting persisted. PHEX and FGF23 gene analyses were negative, whereas serum FGF23 levels were markedly elevated in Patient 1. CONCLUSION: We now demonstrate an association between opsismodysplasia, hypophosphatemic rickets, and FGF23 elevation. Screening phosphorus levels may thus uncover a potentially treatable component of this disease.