Novel GALNT3 mutations causing hyperostosis-hyperphosphatemia syndrome result in low intact fibroblast growth factor 23 concentrations
Novel GALNT3 mutations causing hyperostosis-hyperphosphatemia syndrome result in low intact fibroblast growth factor 23 concentrations
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DOI：
10.1210/jc.2006-1825
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发表时间：
2007-05-01
影响因子：
5.8
通讯作者：
Econs, Michael J.
中科院分区：
文献类型：
--
作者：
Ichikawa, Shoji;Guigonis, Vincent;Econs, Michael J.
背景：骨质疏松症-高磷血症综合征(HHS)是一种罕见的以高磷血症和局限性骨质增生症为特征的代谢紊乱。HHS是由编码UDP-N-乙酰-α-D-半乳糖胺：多肽N-乙酰氨基半乳糖转移酶3的GALNT3突变引起的。家族性肿瘤钙质沉着症(TC)以异位钙化和高磷血症为特征，由GALNT3或成纤维细胞生长因子23(FGF23)基因突变引起。目的：我们的目的是鉴定HHS患者FGF23或GALNT3的突变并测定血清FGF23水平。设计：通过DNA测序检测FGF23和GALNT3的突变，患者或其他参与者：一名患有HHS的5岁法国男孩及其家人参与其中。结果：患者出现腿部疼痛的皮质损害。受累骨骼的X线片显示骨干骨质增生。皮损组织由未成熟的编织骨小梁组成，周围环绕纤维组织。生化检查显示磷酸盐升高，肾小球滤液每分升肾小管最大磷酸盐重吸收速率和1，25-二羟基维生素D水平升高。患者是两个新的GALNT3突变的复合杂合子。他的父母和兄弟都是其中一个突变的杂合子，没有生化异常。结论：HHS患者存在GALNT3基因突变，C端水平升高，但血清FGF23水平低，与TC相似，提示HHS与TC是同一疾病的不同表现。杂合子个体中没有生化异常，表明一个正常等位基因足以分泌完整的FGF23。
Context: Hyperostosis-hyperphosphatemia syndrome (HHS) is a rare metabolic disorder characterized by hyperphosphatemia and localized hyperostosis. HHS is caused by mutations in GALNT3, which encodes UDP-N-acetyl-alpha-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase 3. Familial tumoral calcinosis (TC), characterized by ectopic calcifications and hyperphosphatemia, is caused by mutations in the GALNT3 or fibroblast growth factor 23 (FGF23) genes.Objective: Our objective was to identify mutations in FGF23 or GALNT3 and determine serum FGF23 levels in an HHS patient.Design: Mutation detection in FGF23 and GALNT3 was performed by DNA sequencing, and serum FGF23 concentrations were measured by ELISA.Patients or Other Participants: A5-year-old French boy with HHS and his family members participated.Results: The patient presented with painful cortical lesions in his leg. Radiographs of the affected bone showed diaphyseal hyperostosis. The lesional tissue comprised trabeculae of immature, woven bone surrounded by fibrous tissue. Biochemistry revealed elevated phosphate, tubular maximum rate for phosphate reabsorption per deciliter of glomerular filtrate, and 1,25-dihydroxyvitamin D levels. The patient was a compound heterozygote for two novel GALNT3 mutations. His parents and brother were heterozygous for one of the mutations and had no biochemical abnormalities. Intact FGF23 level in the patient was low normal, whereas C-terminal FGF23 was elevated, a pattern similar to TC.Conclusion: The presence of GALNT3 mutations and elevated C-terminal, but low intact serum FGF23, levels in HHS resemble those seen in TC, suggesting that HHS and TC are different manifestations of the same disorder. The absence of biochemical abnormalities in the heterozygous individuals suggests that one normal allele is sufficient for secretion of intact FGF23.