Setchell K D, Bragetti P, Zimmer-Nechemias L, Daugherty C, Pelli M A, Vaccaro R, Gentili G, Distrutti E, Dozzini G, Morelli A
Division of Clinical Mass Spectrometry, Children's Hospital Medical Center, Cincinnati, Ohio 45229-2899.
Hepatology. 1992 Feb;15(2):198-207. doi: 10.1002/hep.1840150206.
The cerebrohepatorenal syndrome of Zellweger is a congenital syndrome of multiple manifestations, including hepatomegaly and liver dysfunction. Treatment is generally of a supportive nature, aimed at improving nutrition and growth, controlling the central nervous system symptoms and limiting progression of liver disease. Because the liver disease in Zellweger syndrome may be attributed to an overproduction and accumulation of cholestanoic acids, exacerbated by diminished primary bile acid synthesis, we hypothesized that primary bile acid administration would be beneficial in improving liver function by a mechanism involving down-regulation in the synthesis of these atypical bile acids. We report here the clinical and biochemical responses to primary bile acid administration in a 2-mo-old boy who was seen with the typical signs of Zellweger syndrome. Liver disease was evident from hepatomegaly and elevated serum liver enzymes and bilirubin. The diagnosis was supported by markedly elevated serum very long chain fatty acids and the bile acids dihydroxycholestanoic acid and trihydroxycholestanoic acid. Confirmation of the lack of peroxisomes was established by electron microscopy. When the patient was 6 mo old, the primary bile acids cholic acid and chenodeoxycholic acid, (100 mg each/day) were administered orally. A significant improvement in biochemical indices of liver function occurred with a normalization of the serum bilirubin and liver enzymes and a histological improvement in the extent of inflammation and bile duct proliferation and disappearance of cannalicular plugs. Serum and urinary cholestanoic acids showed a significant decrease within a few days. A striking and sustained increase in growth was observed after therapy, and an improvement in neurological symptoms was noted. In conclusion, this study indicates that primary bile acid therapy improves liver function and growth in the patient with peroxisomal dysfunction and should be considered in the supportive therapies for this condition.
泽韦格脑肝肾综合征是一种具有多种表现的先天性综合征，包括肝肿大和肝功能障碍。治疗通常是支持性的，旨在改善营养和生长、控制中枢神经系统症状并限制肝脏疾病的进展。由于泽韦格综合征中的肝脏疾病可能归因于胆甾烷酸的过度产生和积累，而初级胆汁酸合成减少会加剧这种情况，我们推测给予初级胆汁酸可能通过一种涉及下调这些非典型胆汁酸合成的机制来改善肝功能。我们在此报告一名2个月大患有典型泽韦格综合征体征男孩接受初级胆汁酸治疗后的临床和生化反应。从肝肿大以及血清肝酶和胆红素升高可明显看出存在肝脏疾病。血清中极长链脂肪酸以及胆汁酸二羟基胆甾烷酸和三羟基胆甾烷酸显著升高支持了该诊断。通过电子显微镜证实了过氧化物酶体缺乏。当患者6个月大时，口服给予初级胆汁酸胆酸和鹅去氧胆酸（各100毫克/天）。肝功能的生化指标有显著改善，血清胆红素和肝酶恢复正常，炎症程度、胆管增生以及胆小管堵塞消失方面有组织学改善。血清和尿胆甾烷酸在数天内显著下降。治疗后观察到生长显著且持续增加，并且注意到神经症状有所改善。总之，本研究表明初级胆汁酸疗法可改善过氧化物酶体功能障碍患者的肝功能和生长，在这种疾病的支持性治疗中应予以考虑。
