Hypoalbuminemia in early-onset dentatorubralpallidoluysian atrophy due to leakage of albumin in multiple organs
Hypoalbuminemia in early-onset dentatorubralpallidoluysian atrophy due to leakage of albumin in multiple organs
复制标题
由于多器官白蛋白渗漏导致早发性齿状核红斑苍白球路易体萎缩的低白蛋白血症
DOI：
10.1007/s00415-012-6787-9
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发表时间：
2013
期刊：
影响因子：
6
通讯作者：
Matsuoka K
中科院分区：
文献类型：
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作者：
Nagai S;Saito Y;Endo Y;Saito T;Kenji Sugai K;Ishiyama A;Komaki H;Nakagawa E;Sasaki M;Ito K;Saito Y;Sukigara S;Ito M;Goto Y;Ito S;Matsuoka K
我们描述了齿状红核-苍白球路易体萎缩症（DRPLA）中低白蛋白血症的并发症，我们发现这种并发症在这种疾病中很常见。此外，我们还通过临床和组织学检查探讨了这种现象的发病机制。对 9 名儿童期发病的 DRPLA 患者（年龄 6-49 岁；CAG 重复长度 62-93）的临床病程和实验室检查结果进行了回顾性审查。通过组织病理学和免疫组织化学分析对三名患者的尸检标本进行了检查。 8 名 DRPLA 患者在疾病初始阶段（年龄，2-32 岁）表现出低蛋白血症 <3.5 g/dl，这与每位患者的 CAG 重复长度相关。六名患者的病情恶化，通常由发热感染引发，并伴有尿蛋白排泄增加。一名患者表现出粪便 α1-抗胰蛋白酶增加，而另一名患者则表现出静脉输注后放射性白蛋白在泌尿道和胃肠道中积聚。免疫组织化学显示大脑白质血管周围区域含有白蛋白单核细胞和星形胶质细胞。注意到肾小球毛细血管中的液体聚集。使用针对扩展的聚谷氨酰胺（polyQ）多肽的抗体进行的免疫标记在大脑皮层神经元、肝细胞、肾集合管和肾小球足细胞中呈阳性，这些细胞充当血清蛋白的过滤屏障。在疾病后期，血清白蛋白似乎很容易从 DRPLA 某些内脏器官的血管中渗漏，特别是在 CAG 重复大幅扩大的患者的肾脏中。我们假设足细胞中具有扩展的polyQ序列的DRPLA基因产物的积累导致肾小球滤过屏障功能障碍。
We delineate a complication of hypoalbuminemia in dentatorubral−pallidoluysian atrophy (DRPLA), which we have found to be common in this disorder. In addition, we explored the pathogenesis of this phenomenon through clinical and histological examinations. Clinical course and laboratory findings of nine patients with childhood-onset DRPLA (aged 6–49 years; CAG repeat length 62–93) were retrospectively reviewed. Autopsied specimens from three patients were examined by histopathological and immunohistochemical analyses. Eight DRPLA patients showed hypoalbuminemia <3.5 g/dl in the initial stages of the disease (age, 2–32 years), which correlated with the CAG repeat length in each patient. Disease worsened in six patients, often triggered by febrile infections and accompanied by increased urinary protein excretion. One patient showed increased fecal α1-antitripsin while another showed accumulation of radioactive albumin in the urinary and gastrointestinal tracts after intravenous infusion. Immunohistochemistry revealed albumin-containing monocytes and astrocytes in the perivascular areas of the cerebral white matter. Fluid collection in the glomerular capillaries was noted. Immunolabeling using antibodies against the expanded polyglutamine (polyQ) polypeptide was positive in cerebral cortical neurons, hepatocytes, renal collecting ducts, and glomerular podocytes, which act as filtration barrier against serum proteins. Serum albumin appears to easily leak from blood vessels in certain visceral organs in DRPLA during later stages of the illness, particularly in the kidneys of patients with largely expanded CAG repeats. We hypothesize that the accumulation of the DRPLA gene product with expanded polyQ sequences in the podocytes results in the dysfunction of the glomerular filtration barrier.