{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T01:09:03Z","timestamp":1788916143601,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,3,22]],"date-time":"2014-03-22T00:00:00Z","timestamp":1395446400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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 \u03b3\u2010glutamyl\u2010transpeptidase. Analysis of urine by electrospray ionisation tandem mass spectrometry (ESI\u2010MS\/MS) showed that the major peaks were <jats:italic>m\/z<\/jats:italic> 480 (taurine\u2010conjugated 3\u03b2\u2010hydroxy\u20105\u2010cholenoic acid) and <jats:italic>m\/z<\/jats:italic> 453 (sulphated 3\u03b2\u2010hydroxy\u20105\u2010cholenoic acid). Analysis of plasma by gas chromatography\u2010mass spectrometry (GC\u2010MS) showed increased concentrations of 3\u03b2\u2010hydroxy\u20105\u2010cholenoic acid, 3\u03b2\u2010hydroxy\u20105\u2010cholestenoic acid and 27\u2010hydroxycholesterol, indicating oxysterol 7\u03b1\u2010hydroxylase deficiency. The patient was homozygous for a mutation (c.1249C&gt;T) in <jats:italic>CYP7B1<\/jats:italic> that alters a highly conserved residue in oxysterol 7\u03b1\u2010hydroxylase (p.R417C) \u2013 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\u03b2\u2010hydroxy\u2010\u0394<jats:sup>5<\/jats:sup> 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\u2010hydroxylase \u2013 the first step in the acidic pathway for bile acid synthesis.<\/jats:p>","DOI":"10.1007\/s10545-014-9695-6","type":"journal-article","created":{"date-parts":[[2014,3,21]],"date-time":"2014-03-21T15:01:47Z","timestamp":1395414107000},"page":"851-861","source":"Crossref","is-referenced-by-count":72,"title":["Liver disease in infancy caused by oxysterol 7\u03b1\u2010hydroxylase deficiency: successful treatment with chenodeoxycholic acid"],"prefix":"10.1002","volume":"37","author":[{"given":"Dongling","family":"Dai","sequence":"first","affiliation":[{"name":"Clinical and Molecular Genetics Unit UCL Institute of Child Health London WC1N 1EH UK"},{"name":"Department of Gastroenterology Shenzhen Children's Hospital 7019 YiTian Road, FuTian District Shenzhen 518026 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippa 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