Profile of Urinary Bile Acids in Infants and Children: Developmental Pattern of Excretion of Unsaturated Ketonic Bile Acids and 7 β-Hydroxylated Bile Acids

Kimura, Akihiko; Mahara, Reijiro; Inoue, Toshiro; Nomura, Yukihiro; Murai, Tsuyoshi; Kurosawa, Takao; Tohma, Masahiko; Noguchi, Kei; Hoshiyama, Atsuo; Fujisawa, Tomotsumi; Kato, Hirohisa

doi:10.1203/00006450-199904010-00022

Cited by 46 publications

(52 citation statements)

References 35 publications

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“…To investigate whether the BA profile can be used as a marker for predicting patient outcome, we analyzed urine samples collected from 40 patients before 1 year of age because BA composition has been shown to differ among patients of different ages (18). The good prognosis group included 21 patients and the poor prognosis group contained 19 patients.…”

Section: Relationship Of Urinary Ba Profile With Patient Outcomementioning

confidence: 99%

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Prognostic roles of tetrahydroxy bile acids in infantile intrahepatic cholestasis

Lee

Kimura

et al. 2017

Journal of Lipid Research

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Section: Relationship Of Urinary Ba Profile With Patient Outcomementioning

confidence: 99%

“…The urine samples were analyzed by GC-MS as previously described (8,18,19). Urine BA concentrations were corrected for the creatinine (Cre) concentration and expressed as micromoles per millimole of Cre.…”

Section: Urine Sample Collection and Analysis Of Urine Basmentioning

confidence: 99%

Prognostic roles of tetrahydroxy bile acids in infantile intrahepatic cholestasis

Lee

Kimura

et al. 2017

Journal of Lipid Research

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“…After synthesizing relevant unusual bile acids such as 3␤-hydroxy-⌬ 5 (10), 3-oxo-⌬ 4 (11), and allo-bile acids (11), which occur in inborn errors of bile acid synthesis, analysis of the bile acids in urine and serum was undertaken by GC-MS using selected ion monitoring of characteristic fragments of methylester-dimethylethylsilyl ether-methoxime derivatives of bile acids as described previously (11). Before GC-MS analysis, the samples were prepared by enzymatic hydrolysis (cholylglycine hydrolase, 30 U) and solvolysis (sulfatase, 150 U; Sigma Chemical Co. Chemical, St. Louis, MO).…”

Section: Patientmentioning

confidence: 99%

Molecular Genetic and Bile Acid Profiles in Two Japanese Patients With 3β-Hydroxy-Δ5-C27-Steroid Dehydrogenase/Isomerase Deficiency

et al. 2010

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ABSTRACT:We report definitive diagnosis and effective chenodeoxycholic acid (CDCA) treatment of two Japanese children with 3␤-hydroxy-⌬ 5 -C 27 -steroid dehydrogenase/isomerase deficiency. Findings of cholestasis with normal serum ␥-glutamyltransferase activity and total bile acid concentration indicated the need for definitive bile acid analysis. Large amounts of 3␤-hydroxy-⌬ 5 bile acids were detected by gas chromatography-mass spectrometry. HSD3B7 gene analysis using peripheral lymphocyte genomic DNA from the patients and their parents identified four novel mutations of the HSD3B7 gene in the patients. One had a homozygous mutation, 314delA; the other had compound heterozygous mutations: V132F, T149I, and 973_974insCCTGC. Interestingly, the second patient's mother had V132F and T149I mutations in one allele. Excessive 3␤-hydroxy-⌬ 5 -bile acids such as 3␤,7␣-dihydroxy-and 3␤,7␣,12␣-trihydroxy-5-cholenoic acids were detected in the first patient's urine; the second patient's urine contained large amounts of 3␤-hydroxy-5-cholenoic acid. Liver dysfunction in both patients decreased with ursodeoxycholic acid treatment, but unusual bile acids were still detected. Normalization of the patients' liver function and improvement of bile acid profiles occurred with CDCA treatment. Thus, we found mutations in the HSD3B7 gene accounting for autosomal recessive neonatal cholestasis caused by 3␤-hydroxy-⌬ 5 -C 27 -steroid dehydrogenase/isomerase deficiency. Early neonatal diagnosis permits initiation of CDCA treatment at this critical time, before the late cholestatic stage. (Pediatr Res 68: 258-263, 2010) D eficiency of 3␤-hydroxy-⌬ 5 -C 27 -steroid dehydrogenase/ isomerase (3␤-HSD) was first described by Clayton et al. in 1987 (1). This inborn error of bile acid synthesis is very rare and shows autosomal recessive inheritance. The main findings in 3␤-HSD deficiency are low or normal concentrations of total bile acid and normal activity of ␥-glutamyltransferase (GGT) in serum, as well as absence of pruritus despite conjugated hyperbilirubinemia, elevated alanine aminotransferase (ALT), and fatty stools. In the synthesis of bile acids from cholesterol, 3␤-HSD catalyzes the second of a series of reactions leading to excretion of 3␤,7␣-dihydroxy-5-cholenoic acid (⌬ 5 -3␤,7␣-diol) and 3␤,7␣,12␣-trihydroxy-5-cholenoic acid (⌬ 5 -3␤,7␣,12␣-triol) in the urine. In the first reported patient, complete absence of 3␤-HSD activity was found by Buchmann et al. in 1990 (2) based on the study of cultured fibroblasts. In 2000, Schwarz et al. (3) reported that the same patient had a homozygous mutation representing a 2-bp deletion in exon 6 of the 3␤-HSD gene (HSD3B7) on chromosome 16p11.2-12. The human HSD3B7 gene contains six coding exons and encodes 369 amino acids; so far, 13 distinct mutations causing 3␤-HSD deficiency have been reported (4,5).Here, we report genetic analyses of two Japanese patients with 3␤-HSD deficiency: one previously reported patient (6,7) was diagnosed with 3␤-HSD deficiency by bile acid analysis and the ot...

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“…This increase also occurs during cholestasis resulting from biliary atresia. In the urine of infants with biliary atresia, the proportion of 1β-hydroxylated bile acids among TBA increases as cholestasis persists [8,16] . However, as liver function deteriorates, the proportion of 1β-hydroxylated bile acids is reduced while the proportion of ketonic bile acids increases [17] .…”

Section: Discussionmentioning

confidence: 99%

“…Concentrations of individual bile acids in urine were corrected for creatinine concentration (Cr) in each subject, and are expressed as micromoles per millimole of Cr. The samples of human biologic fluids were prepared routinely for GC-MS analysis as described previously [8] . 2 †, at admission; T Bil, total bilirubin; ALT, alanine aminotransferase; GGT, γ-glutamyltransferase; TBA, total bile acids; PEBD, partial external biliary diversion; fs, frameshift.…”

Section: Bile Acid Analysismentioning

confidence: 99%

Clinical Course Following Partial External Biliary Diversion for Progressive Familial Intrahepatic Cholestasis 1: A Report of Two Patients

Kimura

Abukawa²,

Takei³

et al. 2016

Journal of Gastroenterology and Hepatology Research

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AIM:To better understand the effect of partial external biliary diversion (PEBD) in patients with progressive familial intrahepatic cholestasis 1 (PFIC1). MATERIALS AND METHODS:We analyzed quantitative changes in the concentrations of individual bile acids in serum, urine, and biliary bile, and concomitant changes in symptoms such as pruritus, in 2 patients whose PFIC1 clinically evolved to resemble the course of benign recurrent intrahepatic cholestasis (BRIC) upon treatment with PEBD. RESULTS: Patient 1 showed good therapeutic effect after PEBD including improved liver function test results and decreased total bile acids in serum, as well as decreased pruritus. The cholic acid (CA)/chenodeoxycholic acid (CDCA) ratio in biliary bile also decreased. Patient 2, however, experienced little decrease in pruritus after PEBD, and showed no clear change in the CA/CDCA ratio. Nonetheless, this patient's course did not rapidly worsen. CONCLUSION: In PFIC1, increased bile secretion and a decreased CA/CDCA ratio in biliary bile may be the most important responses after PEBD. Relief of pruritus is also an important sign of therapeutic effect. Moreover, progression of symptoms in PFIC1 sometimes can be delayed by PEBD, resulting in a relatively mild BRIC-like course, even when the CA/CDCA ratio and pruritus show little change. However, mechanisms underlying clinical benefits remain obscure. Abbreviations PFIC1: progressive familial intrahepatic cholestasis 1; GGT: γ-glutamyltransferase;

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Profile of Urinary Bile Acids in Infants and Children: Developmental Pattern of Excretion of Unsaturated Ketonic Bile Acids and 7 β-Hydroxylated Bile Acids

Cited by 46 publications

References 35 publications

Prognostic roles of tetrahydroxy bile acids in infantile intrahepatic cholestasis

Prognostic roles of tetrahydroxy bile acids in infantile intrahepatic cholestasis

Molecular Genetic and Bile Acid Profiles in Two Japanese Patients With 3β-Hydroxy-Δ5-C27-Steroid Dehydrogenase/Isomerase Deficiency

Clinical Course Following Partial External Biliary Diversion for Progressive Familial Intrahepatic Cholestasis 1: A Report of Two Patients

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