An inborn error of bile acid synthesis (3 -hydroxy- 5-C27-steroid dehydrogenase deficiency) presenting as malabsorption leading to rickets

Akobeng, Anthony K; Clayton, Peter T.; Miller, Vivien; Super, Maurice; Thomas, Adrian G

doi:10.1136/adc.80.5.463

Cited by 29 publications

(19 citation statements)

References 11 publications

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“…Although the period of conjugated hyperbilirubinaemia was transient in our patient, the finding of rickets at the age of 1 year strongly suggests fat malabsorption, resulting in low levels of vitamin D [12]. The repeatedly elevated levels of ALP were, at the time, interpreted as a sign of rickets.…”

Section: Discussionmentioning

confidence: 69%

Cholestatic liver disease in adults may be due to an inherited defect in bile acid biosynthesis

Fischler

Bodin

Stjernman

et al. 2007

Journal of Internal Medicine

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Section: Discussionmentioning

confidence: 69%

Cholestatic liver disease in adults may be due to an inherited defect in bile acid biosynthesis

Fischler

Bodin

Stjernman

et al. 2007

Journal of Internal Medicine

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“…Interestingly, it may be feasible to increase UDCA intestinal exposure by the use of a specific type of probiotic (living bacteria) that epimerizes CDCA to UDCA within the intestinal lumen [134] . BAs have been used in some cases as a replacement to reduce steatorrhea due to short bowel syndrome or secondary to metabolic genetic diseases, frequently at the price of enhanced diarrhea [135,136] . Conversely, diarrhea without steatorrhea benefits from treatment with ion exchange www.wjgnet.com resins such as cholestiramine that bind and act as sequestrant of BAs during their intestinal transit [137] .…”

Section: Intestinal Applications Of Bamentioning

confidence: 99%

Intestinal bile acid physiology and pathophysiology

Martínez‐Augustin¹,

Medina²

2008

WJG

136

114

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Bile acids (BAs) have a long established role in fat digestion in the intestine by acting as tensioactives, due to their amphipathic characteristics. BAs are reabsorbed very efficiently by the intestinal epithelium and recycled back to the liver via transport mechanisms that have been largely elucidated. The transport and synthesis of BAs are tightly regulated in part by specific plasma membrane receptors and nuclear receptors. In addition to their primary effect, BAs have been claimed to play a role in gastrointestinal cancer, intestinal inflammation and intestinal ionic transport. BAs are not equivalent in any of these biological activities, and structural requirements have been generally identified. In particular, some BAs may be useful for cancer chemoprevention and perhaps in inflammatory bowel disease, although further research is necessary in this field. This review covers the most recent developments in these aspects of BA intestinal biology.

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“…The C 27 3β-HSD enzyme activity is expressed in normal fibroblasts and is absent from these cells in affected individuals (8). Occasional individuals do not develop clinical liver disease as neonates but do present with rickets and failure to thrive in childhood (31). The disease is extremely rare, and only a few patients (approximately six) have been reported in the clinical literature.…”

Section: Figurementioning

confidence: 99%

The bile acid synthetic gene 3β-hydroxy-Δ5-C27-steroid oxidoreductase is mutated in progressive intrahepatic cholestasis

Schwarz¹,

Wright²,

Davis³

et al. 2000

J. Clin. Invest.

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We used expression cloning to isolate cDNAs encoding a microsomal 3β-hydroxy-∆ 5 -C 27 -steroid oxidoreductase (C 27 3β-HSD) that is expressed predominantly in the liver. The predicted product shares 34% sequence identity with the C 19 and C 21 3β-HSD enzymes, which participate in steroid hormone metabolism. When transfected into cultured cells, the cloned C 27 3β-HSD cDNA encodes an enzyme that is active against four 7α-hydroxylated sterols, indicating that a single C 27 3β-HSD enzyme can participate in all known pathways of bile acid synthesis. The expressed enzyme did not metabolize several different C 19/21 steroids as substrates. The levels of hepatic C 27 3β-HSD mRNA in the mouse are not sexually dimorphic and do not change in response to dietary cholesterol or to changes in bile acid pool size. The corresponding human gene on chromosome 16p11.2-12 contains six exons and spans 3 kb of DNA, and we identified a 2-bp deletion in the C27 3β-HSD gene of a patient with neonatal progressive intrahepatic cholestasis. This mutation eliminates the activity of the enzyme in transfected cells. These findings establish the central role of C 27 3β-HSD in the biosynthesis of bile acids and provide molecular tools for the diagnosis of a third type of neonatal progressive intrahepatic cholestasis associated with impaired bile acid synthesis.

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An inborn error of bile acid synthesis (3 -hydroxy- 5-C27-steroid dehydrogenase deficiency) presenting as malabsorption leading to rickets

Abstract: Deficiency of 3 -hydroxy-5

Cited by 29 publications

References 11 publications

Cholestatic liver disease in adults may be due to an inherited defect in bile acid biosynthesis

Cholestatic liver disease in adults may be due to an inherited defect in bile acid biosynthesis

Intestinal bile acid physiology and pathophysiology

The bile acid synthetic gene 3β-hydroxy-Δ5-C27-steroid oxidoreductase is mutated in progressive intrahepatic cholestasis

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