Delta 4-3-oxosteroid 5 beta-reductase deficiency: failure of ursodeoxycholic acid treatment and response to chenodeoxycholic acid plus cholic acid.
BACKGROUND
In some infants with liver disease, 3-oxo-delta 4 bile acids are the major bile acids in urine, a phenomenon attributed to reduced activity of the delta 4-3-oxosteroid 5 beta-reductase required for synthesis of chenodeoxycholic acid and cholic acid. These patients form a heterogeneous group. Many have a known cause of hepatic dysfunction and plasma concentrations of chenodeoxycholic acid and cholic acid that are actually greater than those of the 3-oxo-delta 4 bile acids. It is unlikely that these patients have a primary genetic deficiency of the 5 beta-reductase enzyme.


OBJECTIVE
To document the bile acid profile, clinical phenotype, and response to treatment of an infant with cholestasis, increased plasma concentrations of 3-oxo-delta 4 bile acids, low plasma concentrations of chenodeoxycholic acid and cholic acid, and no other identifiable cause of liver disease.


METHODS
This infant was compared with normal infants and infants with cholestasis of known cause.


METHODS
Analysis of bile acids by liquid secondary ionisation mass spectrometry and gas chromatography-mass spectrometry.


RESULTS
The plasma bile acid profile of the patient was unique. She had chronic cholestatic liver disease associated with malabsorption of vitamins D and E and a normal gamma-glutamyltranspeptidase when the transaminases were increased. The liver disease failed to improve with ursodeoxycholic acid but responded to a combination of chenodeoxycholic acid and cholic acid.


CONCLUSIONS
Treatment of primary 5 beta-reductase deficiency requires the use of bile acids that inhibit cholesterol 7 alpha-hydroxylase.
Clayton
P T
PT
Institute of Child Health, London.
Mills
K A
KA
Johnson
A W
AW
Barabino
A
A
Marazzi
M G
MG
D001647:Bile Acids and Salts / Q000097:blood / Q000627:therapeutic use*; D002635:Chenodeoxycholic Acid / Q000097:blood / Q000627:therapeutic use*; D002756:Cholagogues and Choleretics / Q000097:blood / Q000627:therapeutic use*; D002779:Cholestasis / Q000151:congenital* / Q000188:drug therapy / Q000378:metabolism; D019826:Cholic Acid; D002793:Cholic Acids / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D010088:Oxidoreductases / Q000172:deficiency*; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use
D001647:Bile Acids and Salts; D002756:Cholagogues and Choleretics; D002793:Cholic Acids; D002635:Chenodeoxycholic Acid; D014580:Ursodeoxycholic Acid; D010088:Oxidoreductases; C051860:cholestenone 5 beta-reductase; D019826:Cholic Acid