A novel etiologic factor of highly elevated cholestanol levels: progressive familial intrahepatic cholestasis

Area of Science:

• Hepatology
• Genetics
• Biochemistry

Background:

• Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare cholestatic liver disease resulting from mutations in the ATP binding cassette subfamily B member 4 (ABCB4) gene.
• While often diagnosed in childhood, ABCB4 gene mutations are also implicated in various adult cholestatic conditions, including intrahepatic cholestasis of pregnancy and primary biliary cirrhosis.
• Cholestanol is a biomarker typically elevated in cerebrotendinous xanthomatosis and less commonly in primary biliary cirrhosis and Niemann-Pick type C.

Observation:

• This report details a Turkish patient with compound heterozygous ABCB4 mutations presenting with hepatosplenomegaly, low high-density lipoprotein, cholestasis, and notably, a high cholestanol level.
• This represents the first documented case of PFIC3 associated with elevated cholestanol.

Findings:

• The patient's presentation of PFIC3 with a high cholestanol level is a novel observation.
• The co-occurrence of PFIC3 and elevated cholestanol is significant given the limited number of conditions associated with high cholestanol.

Implications:

• A high cholestanol level may serve as an additional diagnostic indicator for PFIC type 3.
• This case broadens the understanding of cholestanol's role as a biomarker, suggesting its potential utility in diagnosing PFIC3 alongside other cholestatic liver diseases.