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Liver disease in infancy caused by oxysterol 7α-hydroxylase deficiency: successful treatment with chenodeoxycholic acid

, William Griffiths Orcid Logo, Yuqin Wang Orcid Logo

Journal of Inherited Metabolic Disease

Swansea University Authors: William Griffiths Orcid Logo, Yuqin Wang Orcid Logo

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DOI (Published version): 10.1007/s10545-014-9695-6

Abstract

A child of consanguineous parents of Pakistani origin developed jaundice at 5 weeks and then, at 3 months, irritability, a prolonged prothrombin time, a low albumin, and episodes of hypoglycaemia. Investigation showed an elevated alanine aminotransferase with a normal γ-glutamyl-transpeptidase. Anal...

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Published in: Journal of Inherited Metabolic Disease
Published: 2014
URI: https://cronfa.swan.ac.uk/Record/cronfa17814
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first_indexed 2014-04-15T01:30:03Z
last_indexed 2019-09-24T19:18:07Z
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fullrecord <?xml version="1.0"?><rfc1807><datestamp>2019-09-24T16:07:15.8414274</datestamp><bib-version>v2</bib-version><id>17814</id><entry>2014-04-14</entry><title>Liver disease in infancy caused by oxysterol 7&#x3B1;-hydroxylase deficiency: successful treatment with chenodeoxycholic acid</title><swanseaauthors><author><sid>3316b1d1b524be1831790933eed1c26e</sid><ORCID>0000-0002-4129-6616</ORCID><firstname>William</firstname><surname>Griffiths</surname><name>William Griffiths</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>c92729b58622f9fdf6a0e7d8f4ce5081</sid><ORCID>0000-0002-3063-3066</ORCID><firstname>Yuqin</firstname><surname>Wang</surname><name>Yuqin Wang</name><active>true</active><ethesisStudent>false</ethesisStudent></author></swanseaauthors><date>2014-04-14</date><deptcode>BMS</deptcode><abstract>A child of consanguineous parents of Pakistani origin developed jaundice at 5 weeks and then, at 3 months, irritability, a prolonged prothrombin time, a low albumin, and episodes of hypoglycaemia. Investigation showed an elevated alanine aminotransferase with a normal &#x3B3;-glutamyl-transpeptidase. Analysis of urine by electrospray ionisation tandem mass spectrometry (ESI-MS/MS) showed that the major peaks were m/z 480 (taurine-conjugated 3&#x3B2;-hydroxy-5-cholenoic acid) and m/z 453 (sulphated 3&#x3B2;-hydroxy-5-cholenoic acid). Analysis of plasma by gas chromatography-mass spectrometry (GC-MS) showed increased concentrations of 3&#x3B2;-hydroxy-5-cholenoic acid, 3&#x3B2;-hydroxy-5-cholestenoic acid and 27-hydroxycholesterol, indicating oxysterol 7&#x3B1;-hydroxylase deficiency. The patient was homozygous for a mutation (c.1249C&amp;#62;T) in CYP7B1 that alters a highly conserved residue in oxysterol 7&#x3B1;-hydroxylase (p.R417C) - previously reported in a family with hereditary spastic paraplegia type 5. On treatment with ursodeoxycholic acid (UDCA), his condition was worsening, but on chenodeoxycholic acid (CDCA), 15 mg/kg/d, he improved rapidly. A biopsy (after 2 weeks on CDCA), showed a giant cell hepatitis, an evolving micronodular cirrhosis, and steatosis. The improvement in liver function on CDCA was associated with a drop in the plasma concentrations and urinary excretions of the 3&#x3B2;-hydroxy-&#x394;5 bile acids which are considered hepatotoxic. At age 5 years (on CDCA, 6 mg/kg/d), he was thriving with normal liver function. Neurological development was normal apart from a tendency to trip. Examination revealed pes cavus but no upper motor neuron signs. The findings in this case suggest that CDCA can reduce the activity of cholesterol 27-hydroxylase - the first step in the acidic pathway for bile acid synthesis.</abstract><type>Journal Article</type><journal>Journal of Inherited Metabolic Disease</journal><publisher/><keywords/><publishedDay>31</publishedDay><publishedMonth>12</publishedMonth><publishedYear>2014</publishedYear><publishedDate>2014-12-31</publishedDate><doi>10.1007/s10545-014-9695-6</doi><url/><notes/><college>COLLEGE NANME</college><department>Biomedical Sciences</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>BMS</DepartmentCode><institution>Swansea University</institution><apcterm/><lastEdited>2019-09-24T16:07:15.8414274</lastEdited><Created>2014-04-14T16:38:19.8281803</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Medicine</level></path><authors><author><order>1</order></author><author><firstname>William</firstname><surname>Griffiths</surname><orcid>0000-0002-4129-6616</orcid><order>2</order></author><author><firstname>Yuqin</firstname><surname>Wang</surname><orcid>0000-0002-3063-3066</orcid><order>3</order></author></authors><documents/><OutputDurs/></rfc1807>
spelling 2019-09-24T16:07:15.8414274 v2 17814 2014-04-14 Liver disease in infancy caused by oxysterol 7α-hydroxylase deficiency: successful treatment with chenodeoxycholic acid 3316b1d1b524be1831790933eed1c26e 0000-0002-4129-6616 William Griffiths William Griffiths true false c92729b58622f9fdf6a0e7d8f4ce5081 0000-0002-3063-3066 Yuqin Wang Yuqin Wang true false 2014-04-14 BMS A child of consanguineous parents of Pakistani origin developed jaundice at 5 weeks and then, at 3 months, irritability, a prolonged prothrombin time, a low albumin, and episodes of hypoglycaemia. Investigation showed an elevated alanine aminotransferase with a normal γ-glutamyl-transpeptidase. Analysis of urine by electrospray ionisation tandem mass spectrometry (ESI-MS/MS) showed that the major peaks were m/z 480 (taurine-conjugated 3β-hydroxy-5-cholenoic acid) and m/z 453 (sulphated 3β-hydroxy-5-cholenoic acid). Analysis of plasma by gas chromatography-mass spectrometry (GC-MS) showed increased concentrations of 3β-hydroxy-5-cholenoic acid, 3β-hydroxy-5-cholestenoic acid and 27-hydroxycholesterol, indicating oxysterol 7α-hydroxylase deficiency. The patient was homozygous for a mutation (c.1249C&#62;T) in CYP7B1 that alters a highly conserved residue in oxysterol 7α-hydroxylase (p.R417C) - previously reported in a family with hereditary spastic paraplegia type 5. On treatment with ursodeoxycholic acid (UDCA), his condition was worsening, but on chenodeoxycholic acid (CDCA), 15 mg/kg/d, he improved rapidly. A biopsy (after 2 weeks on CDCA), showed a giant cell hepatitis, an evolving micronodular cirrhosis, and steatosis. The improvement in liver function on CDCA was associated with a drop in the plasma concentrations and urinary excretions of the 3β-hydroxy-Δ5 bile acids which are considered hepatotoxic. At age 5 years (on CDCA, 6 mg/kg/d), he was thriving with normal liver function. Neurological development was normal apart from a tendency to trip. Examination revealed pes cavus but no upper motor neuron signs. The findings in this case suggest that CDCA can reduce the activity of cholesterol 27-hydroxylase - the first step in the acidic pathway for bile acid synthesis. Journal Article Journal of Inherited Metabolic Disease 31 12 2014 2014-12-31 10.1007/s10545-014-9695-6 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University 2019-09-24T16:07:15.8414274 2014-04-14T16:38:19.8281803 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine 1 William Griffiths 0000-0002-4129-6616 2 Yuqin Wang 0000-0002-3063-3066 3
title Liver disease in infancy caused by oxysterol 7α-hydroxylase deficiency: successful treatment with chenodeoxycholic acid
spellingShingle Liver disease in infancy caused by oxysterol 7α-hydroxylase deficiency: successful treatment with chenodeoxycholic acid
William Griffiths
Yuqin Wang
title_short Liver disease in infancy caused by oxysterol 7α-hydroxylase deficiency: successful treatment with chenodeoxycholic acid
title_full Liver disease in infancy caused by oxysterol 7α-hydroxylase deficiency: successful treatment with chenodeoxycholic acid
title_fullStr Liver disease in infancy caused by oxysterol 7α-hydroxylase deficiency: successful treatment with chenodeoxycholic acid
title_full_unstemmed Liver disease in infancy caused by oxysterol 7α-hydroxylase deficiency: successful treatment with chenodeoxycholic acid
title_sort Liver disease in infancy caused by oxysterol 7α-hydroxylase deficiency: successful treatment with chenodeoxycholic acid
author_id_str_mv 3316b1d1b524be1831790933eed1c26e
c92729b58622f9fdf6a0e7d8f4ce5081
author_id_fullname_str_mv 3316b1d1b524be1831790933eed1c26e_***_William Griffiths
c92729b58622f9fdf6a0e7d8f4ce5081_***_Yuqin Wang
author William Griffiths
Yuqin Wang
author2
William Griffiths
Yuqin Wang
format Journal article
container_title Journal of Inherited Metabolic Disease
publishDate 2014
institution Swansea University
doi_str_mv 10.1007/s10545-014-9695-6
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 0
active_str 0
description A child of consanguineous parents of Pakistani origin developed jaundice at 5 weeks and then, at 3 months, irritability, a prolonged prothrombin time, a low albumin, and episodes of hypoglycaemia. Investigation showed an elevated alanine aminotransferase with a normal γ-glutamyl-transpeptidase. Analysis of urine by electrospray ionisation tandem mass spectrometry (ESI-MS/MS) showed that the major peaks were m/z 480 (taurine-conjugated 3β-hydroxy-5-cholenoic acid) and m/z 453 (sulphated 3β-hydroxy-5-cholenoic acid). Analysis of plasma by gas chromatography-mass spectrometry (GC-MS) showed increased concentrations of 3β-hydroxy-5-cholenoic acid, 3β-hydroxy-5-cholestenoic acid and 27-hydroxycholesterol, indicating oxysterol 7α-hydroxylase deficiency. The patient was homozygous for a mutation (c.1249C&#62;T) in CYP7B1 that alters a highly conserved residue in oxysterol 7α-hydroxylase (p.R417C) - previously reported in a family with hereditary spastic paraplegia type 5. On treatment with ursodeoxycholic acid (UDCA), his condition was worsening, but on chenodeoxycholic acid (CDCA), 15 mg/kg/d, he improved rapidly. A biopsy (after 2 weeks on CDCA), showed a giant cell hepatitis, an evolving micronodular cirrhosis, and steatosis. The improvement in liver function on CDCA was associated with a drop in the plasma concentrations and urinary excretions of the 3β-hydroxy-Δ5 bile acids which are considered hepatotoxic. At age 5 years (on CDCA, 6 mg/kg/d), he was thriving with normal liver function. Neurological development was normal apart from a tendency to trip. Examination revealed pes cavus but no upper motor neuron signs. The findings in this case suggest that CDCA can reduce the activity of cholesterol 27-hydroxylase - the first step in the acidic pathway for bile acid synthesis.
published_date 2014-12-31T03:20:43Z
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score 11.013148

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