Disturbances of mineral metabolism and severe skeletal involvement in a patient with neurofibromatosis type 1

Neurofibromatosis type 1 (NF-1) is an autosomal dominant disorder caused by mutations in NF1 gene encoding neurofibromin protein. Mutations in this gene result in the absence of suppression of the Ras-MAPK pathway, which leads to increased cell proliferation and tumor development. In addition to the classic manifestations of neurofibromatosis (skin manifestations, tumors of the peripheral and cranial nerves, and scoliosis), patients may develop tumors of the endocrine glands: pheochromocytomas/paragangliomas and neuroendocrine tumors. Cases of NF-1 combined with acromegaly, adrenal tumors (including adrenocortical cancer), and primary hyperparathyroidism (PHPT) have been described. In addition, NF-1 is notable for the development of hypophosphatemic osteomalacia in rare cases.

The article presents a description of a clinical case of a combination of PHPT in a patient with NF-1, hypophosphatemia that persisted after successful surgical treatment of PHPT, and severe skeletal involvement with multiple vertebral and non-vertebral fractures, which was assessed as a combination of severe osteoporosis and hypophosphatemic osteomalacia. During treatment with denosumab, teriparatide and alfacalcidol, increase of bone mineral density and normalization of phosphate levels were achieved. Nevertheless, the absence of consolidation of the femoral shaft fracture persists. Few cases of a combination of NF-1 simultaneously with PHPT and hypophosphatemic osteomalacia are described in the literature.

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