遗传性纤维蛋白原A-α链淀粉样变性

Hereditary fibrinogen A alpha chain amyloidosis

目的:系统性淀粉样变性以AL型和AA型常见,近年国外报道遗传性淀粉样变性发生率并不低,常被误诊为AL型。本文通过报道国内首例遗传性纤维蛋白原A-α链淀粉样变性的临床病理特点,加深对遗传性淀粉样变性的认识,提高其诊断率。方法:观察患者的临床病理特点,肾组织进行A蛋白、κ、λ轻链、纤维蛋白原、甲状腺激素结合蛋白、载脂蛋白AI染色,并进行纤维蛋白原A-α链DNA序列分析。结果:本例患者系青年女性,以蛋白尿和高血压起病,肾功能正常,伴肾脏病家族史。组织学改变显示淀粉样物质只沉积于肾小球,而小管间质及血管不受累。肾小球纤维蛋白原A-α链染色阳性,A蛋白、κ、λ轻链、甲状腺激素结合蛋白和载脂蛋白AI染色阴性。基因测序提示存在纤维蛋白原A-α链的基因突变。结论:遗传性纤维蛋白原A-α链淀粉样变性以蛋白尿和高血压起病,淀粉样变性只累及肾小球,小管间质及血管一般很少受累,纤维蛋白原染色是诊断该病的关键,而纤维蛋白原A-α链基因测序则有助于进一步明确诊断。

Objective：Light-chain （AL） amyloidosis and reactive AA amyloidosis are the two most common forms of systemic amyloidosis. However, hereditary systemic amyloidosis has been more and more reported recently which caused by deposition of genetically variant proteins as amyloid fibrils. We first reported the clinical and histologic characters of hereditary fibrinogen A alpha chain amyloidosis in a Chinese woman. Methodology：The clinical data and histologic appearance were analyzed. Immunohistochemical staining of serum A protein, κ and λ chains, transthyretin, apolipoprotein AI and fibrinogen A alpha chain fibril proteins were performed. Fibrinogen A alpha chain DNA analysis was studied. Results ：The young woman patient was clinically characterized by proteinuria and hypertension with normal renal function and familial renal disease history. Renal biopsy showed the amyloid fibrils selectively deposited in enlarged glomeruli without tubular-interstitial and vascular involvement. The amyloid deposits only stained with antibodies to fibrinogen, but not with amyloid A protein or to κ and λ chains, transthyretin, apolipoprotein AI. The mutation of fibrinogen A alpha chain gene was identified. Conclusion：Hereditary fibrinogen A alpha chain frequent present with proteinuria or hypertension. Amyloid deposition occurs predominantly in the glomeruli, rarely in tubular-interstitial and vascular areas. Immunohistochemical staining of fibrinogen and fibrinogen A alpha chain DNA analysis play a very important role in the diagnosis.