Pediatr Gastroenterol Hepatol Nutr.  2019 Sep;22(5):479-486. 10.5223/pghn.2019.22.5.479.

Novel ATP8B1 Gene Mutations in a Child with Progressive Familial Intrahepatic Cholestasis Type 1

• Rhee ES
• Kim YB
• Lee S
• Oh SH
• Lee BH
• Kim KM
• Yoo HW

• KMID: 2457750
• DOI: http://doi.org/10.5223/pghn.2019.22.5.479

Abstract

Progressive familial intrahepatic cholestasis (PFIC) is a group of severe genetic disorders, inherited in an autosomal recessive manner, causing cholestasis of hepatocellular origin, later progressing to biliary cirrhosis and liver failure. This is the first report of PFIC type 1 with novel compound heterozygous mutations in Korea. The patient was presented with intrahepatic cholestasis, a normal level of serum γ-glutamyl transferase, steatorrhea, and growth failure. Genetic testing of this patient revealed novel compound heterozygous mutations (p.Glu585Ter and p.Leu749Pro) in the ATP8B1 gene. After a liver transplantation at age 19 months, the patient developed severe post-transplant steatohepatitis.

Keyword

Intrahepatic cholestasis; ATP8B1; Child

MeSH Terms

Child*
Cholestasis
Cholestasis, Intrahepatic*
Fatty Liver
Genetic Testing
Humans
Korea
Liver Cirrhosis, Biliary
Liver Failure
Liver Transplantation
Steatorrhea
Transferases
Transferases

Figure

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  Fig. 1 Rickets and osteoporosis of right knee in the patient.

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  Fig. 2 Variants of the ATP8B1 gene in the patient. The patient inherited a missense mutation from her mother (L749P) and a nonsense mutation from her father (E585X).

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  Fig. 3 Biopsy of the explanted liver. (A) Mild portal inflammation with focal bile duct absence, periportal and perisinusoidal fibrosis, and moderate cholestasis (H&E, ×400). (B) Bile salt export pump (BSEP) protein was normally distributed on immunohistochemistry (IHC) staining of the patient's liver (IHC with anti-BSEP) (H&E, ×400). (C) Decreased CD10 staining suggested fewer expressed canaliculi (IHC with CD10) (H&E, ×400). (D) Dilated canaliculus with coarse and granular bile and intraductal bile plugs (electron microscopy) (H&E, ×4,000).

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  Fig. 4 Liver biopsy of the patient 4 months after transplantation. The biopsy shows macrovesicular steatosis with focal minimal lobular activity (H&E, ×200).

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