凝溶胶蛋白型淀粉样变性

Hereditary systemic amyloidosis caused by a heterozygous c.640G>A gelsolin mutation

中年女性,病程7个月,临床表现为中等量蛋白尿和高血压,无低蛋白血症和肾功能损害,外院肾活检提示淀粉样变性,为确定类型转至东部战区总医院国家肾脏疾病临床医学研究中心。入院后行腹壁皮肤脂肪活检及直肠黏膜活检均提示淀粉样变性,直肠黏膜组织行免疫球蛋白轻链、A蛋白、白细胞趋化因子2、溶菌酶、淀粉样前体蛋白、甲状腺素转运蛋白、β2微球蛋白染色均阴性。后采集患者及父母外周血行全外显子基因测序,结果显示患者及其父亲凝溶胶蛋白编码基因c.640G>A杂合突变,进一步完善其他家系成员基因检测提示常染色体显性遗传。患者直肠黏膜组织凝溶胶蛋白染色阳性,最终诊断为凝溶胶蛋白型淀粉样变性。

A 48-year-old woman presented with moderate proteinuria and hypertension.A renal biopsy at local hospital indicated amyloidosis.The subcutaneous fat aspirate and rectum mucosa biopsy in our hospital also showed amyloid deposits.However,the immunoglobulin light chains,amyloid A,leukocyte cell-derived chemotaxin 2、lysozyme、amyloid precursor protein、transthyretin andβ2-microglobulin staining were all negative in the rectum mucosa.Furthermore,genetic sequencing reveled the gelsolin mutation(c.640 G>A)in the patient and her father,and futher sequencing of other family members showed autosomal dominant inheritance.Anti-gelsolin staining was positive in rectum mucosa,and the final diagnosed was gelsolin amyloidosis(AGel amyloidosis).