DELTA-4-3-OXOSTEROID 5-BETA-REDUCTASE DEFICIENCY DESCRIBED IN IDENTICAL-TWINS WITH NEONATAL HEPATITIS - A NEW INBORN ERROR IN BILE-ACID SYNTHESIS
DELTA-4-3-OXOSTEROID 5-BETA-REDUCTASE DEFICIENCY DESCRIBED IN IDENTICAL-TWINS WITH NEONATAL HEPATITIS - A NEW INBORN ERROR IN BILE-ACID SYNTHESIS
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DOI：
10.1172/jci113837
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发表时间：
1988-12-01
影响因子：
15.9
通讯作者：
BALISTRERI, WF
中科院分区：
文献类型：
--
作者：
SETCHELL, KDR;SUCHY, FJ;BALISTRERI, WF
描述了一种新的胆汁酸合成先天性缺陷，在同卵双胞胎中表现为严重肝内胆汁淤积，涉及Δ 4 - 3-氧代类固醇5 β-还原酶催化的关键中间体7 α-羟基-4-异戊烯-3-酮和7 α，用于鹅去氧胆酸和胆酸合成的127 α-二羟基-4-异戊烯-3-酮，分别转化为3 α-羟基-57b（H）产物。通过快速原子轰击电离-质谱法从牛磺酸结合的不饱和羟基-氧代-胆汁酸的升高的排泄和优势中检测到这种缺陷。气相色谱-质谱法证实这些是7 α-羟基-3-氧代-4-胆烯酸和7 α，12. alpha. -二羟基-3-氧代-4-胆烯酸（占总量的72 - 92%）。空腹血清胆汁酸浓度> 37 μ mol/升;鹅去氧胆酸是主要的胆汁酸，但显著量的allo（5 α- H）-胆汁酸（约30%）出席。胆汁酸浓度为
A new inborn error in bile acie synthesis, manifest in identical infant twins as severe intrahepatic cholestasis, is described involving the .DELTA.4-3-oxosteroid 5.beta.-reductase catalyzed conversion of the key intermediates, 7.alpha.-hydroxy-4-cholesten-3-one and 7.alpha.,127a-dithydroxy-4-cholesten-3-one for chenodeoxycholic and cholic acid synthesis, to the respective 3.alpha.-hydroxy-57b(H) products. This defect was detected by fast atom bombarment ionization-mass spectrometry from an elevated excretion and predominance of taurine conjugated unsaturated hydroxy-oxo-bile acids. Gas chromatography-mass spectrometry confirmed these to be 7.alpha.-hydroxy-3-oxo-4-cholenoic and 7.alpha.,12.alpha.-dihydroxy-3-oxo-4-cholenoic acids (72-92% of total). Fasting serum bile acid concentrations were > 37 .mu.mol/liter; chenodeoxycholic acid was the major bile acid, but significant amounts of allo (5.alpha.-H)-bile acids (.apprx. 30%) were present. Billiary bile acid concentrations was