Background: Neurofibromatosis type 1 is characterized by multiple café au lait spots and cutaneous and plexiform neurofibromas, and is one of the most common autosomal dominant hereditary disorders caused by mutations of the neurofibromatosis type 1 tumor suppressor gene. Osteomalacia in neurofibromatosis type 1 is very rare and is characterized by later onset in adulthood. In humans, fibroblast growth factor 23, which is a causative factor of tumor-induced osteomalacia, is not only a paracrine and autocrine factor, but is also a physiological regulator of phosphate balance in normal serum.
Case presentation: Our patient was a 65-year-old Japanese woman whose neurofibromas began to appear when she was in elementary school. At age 28, she was diagnosed as having neurofibromatosis type 1. A spinal compression fracture and multiple rib fractures were identified in 2012 and 2017, respectively. Her laboratory findings revealed hypophosphatemia due to renal phosphate wasting and a high serum level of fibroblast growth factor 23. Neurofibromas located on the surface of her right forearm and left upper arm, in which a slight abnormal accumulation of tracers was observed on 111indium-pentetreotide scintigraphy, were surgically removed, but there was no improvement in hypophosphatemia or serum fibroblast growth factor 23 after surgery. Therefore, we administered eldecalcitol, which also failed to produce improvement in abnormal data. Subsequent combination with dibasic calcium phosphate hydrate led to improvement in some of the abnormalities, including hypophosphatemia. Immunohistochemical staining using anti-human fibroblast growth factor 23 antibody revealed slightly positive results, however, only one out of three amplifications of the fibroblast growth factor 23 gene was observed by real-time polymerase chain reaction, and no clear fibroblast growth factor 23 gene expression in the resected neurofibromas could be confirmed.
Conclusions: We here describe a first rare case of a 65-year-old woman with neurofibromatosis type 1 associated with hypophosphatemic osteomalacia in which a high serum fibroblast growth factor 23 level was confirmed.
Keywords: 25-hydroxyvitamin D3; Fibroblast growth factor 23; Hypophosphatemia; Neurofibromatosis type 1; Tumor-induced osteomalacia.