Pediatr Gastroenterol Hepatol Nutr.  2019 Mar;22(2):201-206. 10.5223/pghn.2019.22.2.201.

Benign Recurrent Intrahepatic Cholestasis Type 2 in Siblings with Novel ABCB11 Mutations

• Sohn MJ
• Woo MH
• Seong MW
• Park SS
• Kang GH
• Moon JS
• Ko JS

• KMID: 2440595
• DOI: http://doi.org/10.5223/pghn.2019.22.2.201

Abstract

Benign recurrent intrahepatic cholestasis (BRIC), a rare cause of cholestasis, is characterized by recurrent episodes of cholestasis without permanent liver damage. BRIC type 2 (BRIC2) is an autosomal recessive disorder caused by ABCB11 mutations. A 6-year-old girl had recurrent episodes of jaundice. At two months of age, jaundice and hepatosplenomegaly developed. Liver function tests showed cholestatic hepatitis. A liver biopsy revealed diffuse giant cell transformation, bile duct paucity, intracytoplasmic cholestasis, and periportal fibrosis. An ABCB11 gene study revealed novel compound heterozygous mutations, including c.2075+3A>G in IVS17 and p.R1221K. Liver function test results were normal at 12 months of age. At six years of age, steatorrhea, jaundice, and pruritus developed. Liver function tests improved following administration of phenylbutyrate and rifampicin. Her younger brother developed jaundice at two months of age and his genetic tests revealed the same mutations as his sister. This is the first report of BRIC2 confirmed by ABCB11 mutations in Korean siblings.

Keyword

Cholestasis, intrahepatic; ABCB11; Mutation; Bile salt export pump

MeSH Terms

Bile Ducts
Biopsy
Child
Cholestasis
Cholestasis, Intrahepatic*
Female
Fibrosis
Giant Cells
Hepatitis
Humans
Jaundice
Liver
Liver Function Tests
Pruritus
Rifampin
Siblings*
Steatorrhea
Rifampin

Figure

• 

  Fig. 1 (A) Photomicrograph of the liver biopsy shows diffuse giant cell transformation of hepatocyte, ballooning degeneration, bile duct paucity, moderate portal inflammation and intracytoplasmic cholestasis (initial liver biopsy, H&E stained, ×400), and (B) intracanalicular cholestasis, bile duct paucity, and minimal to mild focal pericellular fibrosis (recurrent state follow up liver biopsy, H&E stained, ×400). H&E: hematoxylin and eosin.

• 

  Fig. 2 (A) Pedigrees of family who were subjected to familial genetic analysis and (B) reverse transcription polymerase chain reactions of ABCB11 gene in both patients showed exon 17 heterozygous deletion.

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