Clinical case 44

/ 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 mmol/L
Conjugated bilirubin 206 mmol/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 mmol/L
Conjugated bilirubin 206 mmol/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.