| Title |
Liver disease in infancy caused by oxysterol 7α‐hydroxylase deficiency: successful treatment with chenodeoxycholic acid
|
|---|---|
| Published in |
Journal of Inherited Metabolic Disease, March 2014
|
| DOI | 10.1007/s10545-014-9695-6 |
| Pubmed ID | |
| Authors |
Dongling Dai, Philippa B. Mills, Emma Footitt, Paul Gissen, Patricia McClean, Jens Stahlschmidt, Isabelle Coupry, Julie Lavie, Fanny Mochel, Cyril Goizet, Tatsuki Mizuochi, Akihiko Kimura, Hiroshi Nittono, Karin Schwarz, Peter J. Crick, Yuqin Wang, William J. Griffiths, Peter T. Clayton |
| 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. 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>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-Δ(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. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 47 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 47 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 8 | 17% |
| Researcher | 6 | 13% |
| Student > Bachelor | 5 | 11% |
| Other | 4 | 9% |
| Student > Doctoral Student | 3 | 6% |
| Other | 9 | 19% |
| Unknown | 12 | 26% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 9 | 19% |
| Agricultural and Biological Sciences | 9 | 19% |
| Biochemistry, Genetics and Molecular Biology | 8 | 17% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 4% |
| Chemistry | 2 | 4% |
| Other | 5 | 11% |
| Unknown | 12 | 26% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 March 2014.
All research outputs
#16,753,682
of 25,621,213 outputs
Outputs from Journal of Inherited Metabolic Disease
#1,561
of 2,012 outputs
Outputs of similar age
#135,666
of 237,934 outputs
Outputs of similar age from Journal of Inherited Metabolic Disease
#15
of 23 outputs
Altmetric has tracked 25,621,213 research outputs across all sources so far. This one is in the 34th percentile – i.e., 34% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,012 research outputs from this source. They receive a mean Attention Score of 4.9. This one is in the 22nd percentile – i.e., 22% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 237,934 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 42nd percentile – i.e., 42% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 23 others from the same source and published within six weeks on either side of this one. This one is in the 39th percentile – i.e., 39% of its contemporaries scored the same or lower than it.