Very rare. Autosomal recessive transmission.

Different types have been identified:

-        Type 1 [MIM 607 765]: mutation of the HSD3B7 gene (16p12-p11.2), coding for 3-beta-hydroxy-delta-5-C27-steroid oxidoreductase.

-        Type 2 [MIM 235 555]: mutation of the AKR1D1 gene (7q33), coding for delta(4)-3-oxosteroid 5-beta-reductase.

-        Type 3 [MIM 613812]: mutation of the CYP7B1 gene (8q12), coding for 7-alpha hydroxylase

-        Type 4 [MIM 214950]: mutation of the AMACR gene (5p13)

-        Type 5 [MIM 616278 ]: mutation of the ABCD3 gene (1p21)

-        Type 6 [MIM 617308]: mutation of the ACOX2 (3p14)

Clinical presentation is heterogeneous:

-        in general, signs of neonatal cholestasis

-        hepatomegaly, with or without splenomegaly

-        jaundice with moderate steatorrhea and malabsorption of lipids and fat-soluble vitamins.

-        pruritus is usually absent.

Liver check-up reveals elevated serum transaminases levels (ASAT, ALAT) with conjugated hyperbilirubinemia and normal gamma-GT. Liver histology shows inflammation, giant cells, signs of cholestasis and hepatic fibrosis of varying degrees. The course of early-onset forms is variable, ranging from spontaneous resolution of jaundice to fulminant disease that can be fatal or require liver transplantation at an early age.

Other presentations: late-onset chronic cholestasis with fat-soluble vitamin malabsorption leading to rickets and/or other complications such as hemorrhagic syndrome (rectorrhagia or intracranial haemorrhage), neuro-axonal dystrophy and night blindness. Extensive fibrosis and/or cirrhosis may also reveal the disease in children and adolescents.

Familial intrahepatic cholestasis type 1 (PFIC1) (see this term) presents a similar phenotype.

Treatment: ADEK vitamins, ursodeoxycholic acid

Anesthetic implications:

check liver function and coagulation

References :

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Updated: June 2025