Clayton P T, Mills K A, Johnson A W, Barabino A, Marazzi M G
Institute of Child Health, London.
Gut. 1996 Apr;38(4):623-8. doi: 10.1136/gut.38.4.623.
In some infants with liver disease, 3-oxo-delta 4 bile acids are the major bile acids in urine, a phenomenon attributed to reduced activity of the delta 4-3-oxosteroid 5 beta-reductase required for synthesis of chenodeoxycholic acid and cholic acid. These patients form a heterogeneous group. Many have a known cause of hepatic dysfunction and plasma concentrations of chenodeoxycholic acid and cholic acid that are actually greater than those of the 3-oxo-delta 4 bile acids. It is unlikely that these patients have a primary genetic deficiency of the 5 beta-reductase enzyme.
To document the bile acid profile, clinical phenotype, and response to treatment of an infant with cholestasis, increased plasma concentrations of 3-oxo-delta 4 bile acids, low plasma concentrations of chenodeoxycholic acid and cholic acid, and no other identifiable cause of liver disease.
This infant was compared with normal infants and infants with cholestasis of known cause.
Analysis of bile acids by liquid secondary ionisation mass spectrometry and gas chromatography-mass spectrometry.
The plasma bile acid profile of the patient was unique. She had chronic cholestatic liver disease associated with malabsorption of vitamins D and E and a normal gamma-glutamyltranspeptidase when the transaminases were increased. The liver disease failed to improve with ursodeoxycholic acid but responded to a combination of chenodeoxycholic acid and cholic acid.
Treatment of primary 5 beta-reductase deficiency requires the use of bile acids that inhibit cholesterol 7 alpha-hydroxylase.
在一些患有肝病的婴儿中，3-氧代-δ4胆汁酸是尿液中的主要胆汁酸，这种现象归因于鹅去氧胆酸和胆酸合成所需的δ4-3-氧代类固醇5β-还原酶活性降低。这些患者构成了一个异质性群体。许多患者有已知的肝功能障碍病因，其鹅去氧胆酸和胆酸的血浆浓度实际上高于3-氧代-δ4胆汁酸。这些患者不太可能存在5β-还原酶的原发性基因缺陷。
记录一名患有胆汁淤积、3-氧代-δ4胆汁酸血浆浓度升高、鹅去氧胆酸和胆酸血浆浓度低且无其他可识别的肝病病因的婴儿的胆汁酸谱、临床表型及对治疗的反应。
将该婴儿与正常婴儿及已知病因的胆汁淤积婴儿进行比较。
通过液相二次离子质谱和气相色谱-质谱分析胆汁酸。
该患者的血浆胆汁酸谱独特。她患有慢性胆汁淤积性肝病，伴有维生素D和E吸收不良，转氨酶升高时γ-谷氨酰转肽酶正常。熊去氧胆酸治疗未能改善肝病，但鹅去氧胆酸和胆酸联合治疗有效。
原发性5β-还原酶缺乏症的治疗需要使用抑制胆固醇7α-羟化酶的胆汁酸。
