/ 03
01
Two females - twins
Born after 38 weeks of gestation from
non-consanguineous parents
History of neonatal cholestasis of
unknown cause with:
At 8 months:
Laboratory investigations:
All classical causes of cholestasis
and liver failure were excluded.
Admitted to hospital
Normal serum GGT activity
Normal serum total bile acids concentration
Steatorrhoea
Low serum vitamin E concentration
Absence of pruritus
Next
These atypical bile acid metabolites were also
present in plasma.
In place of normal primary bile acids, the
profiles showed:
3-oxo-Δ4 precursors of
chenodeoxycholic and cholic acids
(90% of total urinary bile acids)
Associated with 5% of allo bile acids
And low or undetectable levels of
primary bile acids
Canalicular cholestasis
Giant hepatocytes
Portal inflammation
Septal fibrosis
In both cases, the laboratory
findings fulfilled these criteria:
Diagnosis: Δ4-3-oxoR deficiency
Previous
02
3-oxo-Δ4 bile acids represent more than 70%
of total urinary bile acids + allo bile acids
= genetic defect of Δ4-3-oxoR
Liver histology:
Analysis of urinary bile acids
in both girls by FAB-MS
According to previous
recommendations:
Next
Progressive cholestasis
Liver failure
Steatorrhoea
Absence of pruritus
No relevant family history
Low serum vitamin E concentration
Total bilirubin 304 μmol/L
Conjugated bilirubin 206 μmol/L
ATL 144 U/L
Prothrombin time of 35%
Clotting factor V of 39%
In these clinical cases, the initial clinical signs were highly suggestive of a primary bile acid synthesis disorder.
Canalicular cholestasis
Giant hepatocytes
Portal inflammation
Septal fibrosis
Normal serum GGT activity
Normal serum total bile acids
concentration
03
Previous
01 / 03
Two females - twins
Born after 38 weeks of gestation from
non-consanguineous parents
History of neonatal cholestasis of
unknown cause with:
At 8 months:
Laboratory investigations:
All classical causes of cholestasis
and liver failure were excluded.
Admitted to hospital
Normal serum GGT activity
Normal serum total bile acids concentration
Steatorrhoea
Low serum vitamin E concentration
Absence of pruritus
Next
These atypical bile acid metabolites were also
present in plasma.
In place of normal primary bile acids, the
profiles showed:
3-oxo-Δ4 precursors of
chenodeoxycholic and cholic acids
(90% of total urinary bile acids)
Associated with 5% of allo bile acids
And low or undetectable levels of
primary bile acids
Canalicular cholestasis
Giant hepatocytes
Portal inflammation
Septal fibrosis
In both cases, the laboratory
findings fulfilled these criteria:
Diagnosis: Δ4-3-oxoR deficiency
Previous
02 / 03
3-oxo-Δ4 bile acids represent more than 70%
of total urinary bile acids + allo bile acids
= genetic defect of Δ4-3-oxoR
Liver histology:
Analysis of urinary bile acids
in both girls by FAB-MS
According to previous
recommendations:
Next
Progressive cholestasis
Liver failure
Steatorrhoea
Absence of pruritus
No relevant family history
Low serum vitamin E concentration
Total bilirubin 304 μmol/L
Conjugated bilirubin 206 μmol/L
ATL 144 U/L
Prothrombin time of 35%
Clotting factor V of 39%
In these clinical cases, the initial clinical signs were highly
suggestive of a primary bile acid synthesis disorder.
Canalicular cholestasis
Giant hepatocytes
Portal inflammation
Septal fibrosis
Normal serum GGT activity
Normal serum total bile acids
concentration
03 /03
Previous
CLINICAL
SIGNS
LABORATORY
SIGNS
FAMILY
HISTORY
HISTOLOGICAL
SIGNS
4. Gonzales E, Cresteil D, Baussan C, et al. SRD5B1 (AKR1D1) gene analysis in delta(4)-3-oxosteroid 5beta-reductase deficiency: evidence for primary genetic defect. J Hepatol 2004;40(4):716-8.
TH-BAS15EN/01/02/2024
Those requiring urgent treatment:
Biliary atresia
