Cobalamin malabsorption in three siblings due to an abnormal intrinsic factor that is markedly susceptible to acid and proteolysis.
Cobalamin malabsorption in three siblings due to an abnormal intrinsic factor that is markedly susceptible to acid and proteolysis.
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三个兄弟姐妹由于异常的内因子而导致钴胺素吸收不良，该内因子明显易受酸和蛋白水解的影响。
DOI：
10.1172/jci112208
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Allen,RH
中科院分区：
文献类型：
--
作者：
Yang,YM;Ducos,R;Rosenberg,AJ;Catrou,PG;Levine,JS;Podell,ER;Allen,RH
三个兄弟姐妹在他们的第二年的生活与巨幼细胞性贫血，响应肠外钴胺素（Cbl）。Schilling试验小于1%，在添加猪内在因子（IF）后校正为5 - 15%。胃酸分析和胃活检通过光学和电子显微镜检查是正常的。当使用正常人IF-[57 Co]Cbl和兔抗人IF血清（正常，17-66 pmol/ml）进行放射免疫测定（RIA）时，胃液中IF（正常，10-34 pmol/ml）的Cbl结合能力低于3 pmol/ml，IF低于2 pmol/ml。然而，使用兔抗猪IF血清的RIA给出的IF值为4-13 pmol/ml（正常，11-33 pmol/ml）。该物质的表观分子量为40，000（正常IF = 70，000）。胃活检的IF在Cbl结合能力、回肠结合、分子量和两种RIA方面均正常。该IF不同于正常粘膜IF，因为当在37 ° C在酸性pH下或在胃蛋白酶或胰蛋白酶存在下孵育时，它失去了其Cbl结合能力。当[57 Co]Cbl在这些孵育之前与IF结合时，这种损失被延迟。中和和Cbl的稳定作用也在体内得到证实。当加入NaHCO 3和cobinamide（可使Cbl立即与IF结合）重复Schilling试验时，0.4%、0.5%和1.0%同胞的Schilling试验分别增加至2.7%、5.7%和4.3%（P <0.05）。我们得出结论，这些儿童的Cbl吸收不良是由于异常的IF对酸和蛋白水解酶明显敏感，导致其分子量和Cbl结合能力下降，以及抗人IF血清识别的抗原决定簇丢失。图片
Three siblings presented in their second year of life with megaloblastic anemia that responded to parenteral cobalamin (Cbl). Schilling tests were less than 1%, correcting to 5 to 15% after addition of hog intrinsic factor (IF). Gastric acid analysis and gastric biopsies were normal by light and electron microscopy. Gastric juice contained less than 3 pmol/ml of Cbl-binding ability due to IF (normal, 10-34 pmol/ml) and less than 2 pmol/ml of IF when measured with a radioimmunoassay (RIA) using normal human IF-[57Co]Cbl and rabbit anti-human IF serum (normal, 17-66 pmol/ml). However, RIA employing rabbit anti-hog IF serum gave values of 4-13 pmol/ml of IF (normal, 11-33 pmol/ml). This material had an apparent molecular weight of 40,000 (normal IF = 70,000). The IF from gastric biopsies appeared normal in terms of Cbl-binding ability, ileal binding, molecular weight, and both RIAs. This IF differed from normal mucosal IF, in that it lost its Cbl-binding ability when incubated at 37 degrees C at acid pH or in the presence of pepsin or trypsin. This loss was retarded when [57Co]Cbl was bound to the IF before these incubations. The stabilizing effects of neutralization and Cbl were also demonstrated in vivo. Schilling tests for the siblings of 0.4, 0.5, and 1.0% increased to 2.7, 5.7, and 4.3% (P less than 0.05), respectively, when the Schilling tests were repeated with the addition of NaHCO3 and cobinamide (which allows Cbl to bind immediately to IF). We conclude that Cbl malabsorption in these children is due to an abnormal IF that is markedly susceptible to acid and proteolytic enzymes which cause a decrease in its molecular weight and Cbl-binding ability and a loss of antigenic determinants that are recognized by the anti-human IF serum.Images