BACKGROUND Inborn error of bile acid synthesis type 4 is a peroxisomal disease with impaired bile acid synthesis caused by a-methylacyl-CoA racemase(AMACR)gene mutation.The disease is usually found in children with mi...BACKGROUND Inborn error of bile acid synthesis type 4 is a peroxisomal disease with impaired bile acid synthesis caused by a-methylacyl-CoA racemase(AMACR)gene mutation.The disease is usually found in children with mild to severe liver disease,cholestasis and poor fat-soluble vitamin absorption.At present,there is no report of inborn errors of bile acid synthesis type 4 in adults with liver disease and poor fat-soluble vitamin absorption.CASE SUMMARY A 71-year-old man was hospitalized in our department for recurrent liver dysfunction.The clinical manifestations were chronic liver disease and yellow skin and sclera.Serum transaminase,bilirubin and bile acid were abnormally increased;and fat-soluble vitamins decreased.Liver cirrhosis and ascites were diagnosed by computed tomography.The patient had poor coagulation function and ascites and did not undergo liver puncture.Genetic testing showed AMACR gene missense mutation.The patient was diagnosed with inborn error of bile acid synthesis type 4.He was treated with ursodeoxycholic acid,liver protection and vitamin supplementation,and jaundice of the skin and sclera was reduced.The indicators of liver function and the quality of life were significantly improved.CONCLUSION When adults have recurrent liver function abnormalities,physicians should be alert to genetic diseases and provide timely treatment.展开更多
Steroid 5β-reductase [aldo-keto reductase family 1 member D1(AKR1D1)] is essential for bile acid biosynthesis. Bile acid deficiency caused by genetic defects in AKR1D1 leads to life-threatening neonatal hepatitis and...Steroid 5β-reductase [aldo-keto reductase family 1 member D1(AKR1D1)] is essential for bile acid biosynthesis. Bile acid deficiency caused by genetic defects in AKR1D1 leads to life-threatening neonatal hepatitis and cholestasis. There is still limited experience regarding the treatment of this disease. We describe an infant who presented with hyperbilirubinemia and coagulopathy but normal bile acid and γ-glutamyltransferase. Gene analysis was performed using genomic DNA from peripheral lymphocytes from the patient, his parents, and his elder brother. The patient was compound heterozygous for c.919C>T in exon 8 and exhibited a loss of heterozygosity of the AKR1D1 gene, which led to an amino acid substitution of arginine by cysteine at amino acid position 307(p.R307C). Based on these mutations, the patient was confirmed to have primary 5β-reductase deficiency. Ursodeoxycholic acid(UDCA) treatment did not have any effect on the patient. However, when we changed to chenodeoxycholic acid(CDCA) treatment, his symptoms and laboratory tests gradually improved. It is therefore crucial to supplement with an adequate dose of CDCA early to improve clinical symptoms and to normalize laboratory tests.展开更多
文摘BACKGROUND Inborn error of bile acid synthesis type 4 is a peroxisomal disease with impaired bile acid synthesis caused by a-methylacyl-CoA racemase(AMACR)gene mutation.The disease is usually found in children with mild to severe liver disease,cholestasis and poor fat-soluble vitamin absorption.At present,there is no report of inborn errors of bile acid synthesis type 4 in adults with liver disease and poor fat-soluble vitamin absorption.CASE SUMMARY A 71-year-old man was hospitalized in our department for recurrent liver dysfunction.The clinical manifestations were chronic liver disease and yellow skin and sclera.Serum transaminase,bilirubin and bile acid were abnormally increased;and fat-soluble vitamins decreased.Liver cirrhosis and ascites were diagnosed by computed tomography.The patient had poor coagulation function and ascites and did not undergo liver puncture.Genetic testing showed AMACR gene missense mutation.The patient was diagnosed with inborn error of bile acid synthesis type 4.He was treated with ursodeoxycholic acid,liver protection and vitamin supplementation,and jaundice of the skin and sclera was reduced.The indicators of liver function and the quality of life were significantly improved.CONCLUSION When adults have recurrent liver function abnormalities,physicians should be alert to genetic diseases and provide timely treatment.
基金the Guangdong Medical Research Foundation,No.A2018550
文摘Steroid 5β-reductase [aldo-keto reductase family 1 member D1(AKR1D1)] is essential for bile acid biosynthesis. Bile acid deficiency caused by genetic defects in AKR1D1 leads to life-threatening neonatal hepatitis and cholestasis. There is still limited experience regarding the treatment of this disease. We describe an infant who presented with hyperbilirubinemia and coagulopathy but normal bile acid and γ-glutamyltransferase. Gene analysis was performed using genomic DNA from peripheral lymphocytes from the patient, his parents, and his elder brother. The patient was compound heterozygous for c.919C>T in exon 8 and exhibited a loss of heterozygosity of the AKR1D1 gene, which led to an amino acid substitution of arginine by cysteine at amino acid position 307(p.R307C). Based on these mutations, the patient was confirmed to have primary 5β-reductase deficiency. Ursodeoxycholic acid(UDCA) treatment did not have any effect on the patient. However, when we changed to chenodeoxycholic acid(CDCA) treatment, his symptoms and laboratory tests gradually improved. It is therefore crucial to supplement with an adequate dose of CDCA early to improve clinical symptoms and to normalize laboratory tests.
