Resolution of liver biopsy alterations in three siblings with bile acid treatment of an inborn error of bile acid metabolism (Δ4-3-oxosteroid 5β-reductase deficiency)
✍ Scribed by Ynthia C. Daugherty; Kenneth D. R. Setchell; James E. Heubi; William F. Ballstreri
- Publisher
- John Wiley and Sons
- Year
- 1993
- Tongue
- English
- Weight
- 990 KB
- Volume
- 18
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
Identical male twins and their brother, cholestatic from birth, with A4-3-oxosteroid 5p-reductase deficiency, were studied by serial liver biopsy. Spectrometry documented defective primary bile acid syn- thesis and markedly increased levels of atypical 0x0 and all0 bile acids in urine and serum. Hepatocellular cholestasis and giant-cell transformation resolved in parallel with clinical and biochemical recovery during oral bile acid administration. In the twins, portal fibrosis stabilized at a mild level; they are well as 5-yr-olds at this writing. Follow-up biopsy in their brother at 8 mo was normal, and he is doing well at 3 yr of age. Hepatic ultrastructural alterations in all three were characterized by abnormalities of bile canaliculi including small bile plugs, diverticulae and latticelike elaborations of hepatocellular membranes adjacent to bile canaliculi that were shown to have resolved completely on subsequent biopsies. Eight additional cases have been detected on urine screening; only two of these patients have survived, on bile acid therapy. Early diagnosis and treatment improves the prognosis of this otherwise lethal inborn error of bile acid synthesis. (HEPATOLOGY 1993;18:1096-1101.) Inborn errors of bile acid synthesis, long postulated to be pathogenic in some cases of neonatal cholestasis, can now be biochemically documented (1). The best known of the previously defined defects include those associated with impaired peroxisomal oxidation of the cholesterol side chain in diseases such as Zellweger and pseudo-Zellweger syndromes, infantile Refsum's disease, neonatal adrenoleukodystrophy and cerebrotendinous xanthomatosis (2). Patients with these disorders are cholestatic but do not have histological giant-cell hepatitis.
A defect involving the 3P-hydroxysteroid dehydrogenaselisomerase-catalyzed metabolism of 7a-hydroxycholesterol has been described in children with familial