期刊
BONE
卷 67, 期 -, 页码 56-62出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bone.2014.06.026
关键词
FAM20C; Hypophosphatemic rickets; FGF23; Loss of teeth; OPLL; Cortical hyperostosis
资金
- Ministry of :Health, Labour, and Welfare of Japan [H23-Nanti-007, 11KJB530007: H24-Nanti-040]
- Grants-in-Aid for Scientific Research [24591353, 25860858] Funding Source: KAKEN
Background: Hypophosphatemia and increased serum fibroblast growth factor 23 (FGF23) levels have been reported in young brothers with compound heterozygous mutations for the FAM20C gene; however, rickets was not observed in these cases. We report an adult case of Raine syndrome accompanying hypophosphatemic osteomalacia with a homozygous FAM20C mutation (R408W) associated with increased periosteal bone formation in the long bones and an increase in bone mineral density in the femoral necic. Case: The patient, a 61-year-old man, was born from a cousin-to-cousin marriage. A short stature and severe dental demineralization were reported at an elementary school age. Hypophosphatemia was noted inadvertently at 27 years old, at which time he started to take an active vitamin D metabolite (alphacalcidol) and phosphate. He also manifested ossification of the posterior longitudinal ligament. On bone biopsy performed at the age of 41 years, we found severe osteomalacia surrounding osteocytes, which appeared to be an advanced form of periosteocytic hypomineralized lesions compared to those reported inpatients with X-linked hypophosphatemic rickets. Laboratory data at 61 years of age revealed markedly increased serum intact-FGF23 levels, which were likely to be the cause of hypophosphatemia and the decreased level of 1,25(OH)(2)D. We recently identified a homozygous FAM20C mutation, which was R408W in this patient. When expressed in HEK293 cells, the R408W mutant protein exhibited impaired kinase activity and secretion. Discussion: Our findings suggest that certain homozygous FAM20C mutations can cause FGF23-related hypophosphatemic osteomalacia and indicate the multiple roles of FAM20C in bone. (C) 2014 Elsevier Inc. All rights reserved.
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