Treatment of bile acid amidation defects with glycocholic acid.
Treatment of bile acid amidation defects with glycocholic acid.
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DOI：
10.1002/hep.27401
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发表时间：
2015-01
期刊：
影响因子：
13.5
通讯作者：
Suskind, David
中科院分区：
文献类型：
--
作者：
Heubi, James E.;Setchell, Kenneth D. R.;Jha, Pinky;Buckley, Donna;Zhang, Wujuan;Rosenthal, Philip;Potter, Carol;Horslen, Simon;Suskind, David
预计胆汁酸酰胺化缺陷表现为脂肪/脂溶性维生素吸收不良伴轻微胆汁淤积。我们确定并治疗了来自4个家族的5名患者（1名男性/4名女性），这些患者由于经遗传学证实的胆汁酸CoA：氨基酸N-酰基转移酶（BAAT）与结合胆汁酸甘氨胆酸（GCA）缺乏而患有胆汁酸酰胺化缺陷。基线时尿液和胆汁的快速原子轰击-质谱分析显示主要为非结合胆酸，不存在通常的甘氨酸和牛磺酸结合初级胆汁酸。15 mg/kg GCA给药导致总十二指肠胆汁酸浓度为23.3 ± 19.1 mmol/L（平均值± SD），63.5 ± 4.0%的胆汁酸以结合形式分泌到胆汁中，其中GCA占总胆汁胆汁酸的59.6 ± 9.3%。由于口服GCA的部分肠道去结合，胆汁中的未结合胆酸继续以高浓度存在。治疗前和治疗后样本之间的血清总胆汁酸浓度无显著差异，血清主要含有非结合胆酸。这些结果证实了给予的GCA的有效肠吸收、肝提取和胆汁分泌。维生素D2（1000 IU维生素D2/kg）和生育酚（100 IU/kg生育酚醋酸酯）的口服耐受性试验表明，GCA治疗后脂溶性维生素吸收改善。3/3生长延迟的青春期前患者的生长得到改善。结论：口服甘氨胆酸治疗可安全有效地改善因酰胺化缺陷导致先天性胆汁酸代谢缺陷的儿童和青少年的生长和脂溶性维生素吸收。
Bile acid amidation defects were predicted to present with fat/fat soluble vitamin malabsorption with minimal cholestasis. We identified and treated 5 patients (1 male/4 females) from 4 families with defective bile acid amidation due to a genetically confirmed deficiency in bile acid CoA:amino acid N-acyl transferase (BAAT) with the conjugated bile acid, glycocholic acid (GCA). Fast atom bombardment-mass spectrometry analysis of urine and bile at baseline revealed predominantly unconjugated cholic acid and absence of the usual glycine and taurine conjugated primary bile acids. Treatment with 15 mg/kg GCA resulted in total duodenal bile acid concentrations of 23.3 ± 19.1 mmol/L (mean ± SD) and 63.5 ± 4.0% of the bile acids were secreted in bile in the conjugated form of which GCA represented 59.6 ± 9.3% of the total biliary bile acids. Unconjugated cholic acid continued to be present in high concentrations in bile because of partial intestinal deconjugation of orally administered GCA. Serum total bile acid concentrations did not significantly differ between pretreatment and post-treatment samples and serum contained predominantly unconjugated cholic acid. These findings confirmed efficient intestinal absorption, hepatic extraction and biliary secretion of the administered GCA. Oral tolerance tests for vitamin D2 (1000 IU vitamin D2/kg) and tocopherol (100 IU/kg tocopherol acetate) demonstrated improvement in fat-soluble vitamin absorption after GCA treatment. Growth improved in 3/3 growth-delayed prepubertal patients. Conclusions: Oral glycocholic acid therapy is safe and effective in improving growth and fat-soluble vitamin absorption in children and adolescents with inborn errors of bile acid metabolism due to amidation defects.
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影响因子：
7.1
作者：
BIERI, JG;TOLLIVER, TJ;CATIGNANI, GL
通讯作者：
CATIGNANI, GL
DOI：
10.1016/0378-4347(92)80445-v
发表时间：
1992-10-02
期刊：
JOURNAL OF CHROMATOGRAPHY-BIOMEDICAL APPLICATIONS
影响因子：
--
作者：
LEE, BL;CHUA, SC;ONG, CN
通讯作者：
ONG, CN
胆汁酸偶联的遗传缺陷会导致脂溶性维生素缺乏症。
影响因子：
29.4
作者：
Setchell KD;Heubi JE;Shah S;Lavine JE;Suskind D;Al-Edreesi M;Potter C;Russell DW;O'Connell NC;Wolfe B;Jha P;Zhang W;Bove KE;Knisely AS;Hofmann AF;Rosenthal P;Bull LN
通讯作者：
Bull LN
影响因子：
15.9
作者：
HEPNER, GW;HOFMANN, AF;THOMAS, PJ
通讯作者：
THOMAS, PJ
影响因子：
30.8
作者：
Carlton, VEH;Harris, BZ;Bull, LN
通讯作者：
Bull, LN