Gradual improvement of liver function after administration of ursodeoxycholic acid in an infant with a novel ABCB11 gene mutation with phenotypic continuum between BRIC2 and PFIC2.
OBJECTIVE
The authors report the case of a boy with PFIC type 2 or BRIC type 2 who suffered from liver dysfunction at 2 months after birth.


RESULTS
A liver biopsy specimen revealed mild liver cirrhosis, and the findings resembled those observed in Byler disease. Genetic examination revealed a normal familial intrahepatic cholestasis-1 gene, but a heterozygous mutation for the ABCB11, C1620A (F540L), was observed. Therefore, the patient was initially diagnosed with PFIC type 2. For 3 years after the diagnosis, he had severe pruritus, an increased serum bile acid, and normal serum values of gamma-glutamyl transaminase. At the age of 2, treatment with administration of ursodeoxycholic acid was started; subsequently, a gradual improvement in his liver function was observed. At the age of 3, he suffered from massive intestinal and pulmonary hemorrhage, which improved immediately after the administration of vitamin K. He was then admitted to our hospital for liver transplantation. At 1 month after the admission, his liver dysfunction showed further improvement, except for a mild increase in the serum bile acid level. This condition did not show any change during the 5-year follow-up period. In addition, the patient showed severe growth failure and was diagnosed with growth hormone deficiency. Hence, he receives growth hormone administration.


CONCLUSIONS
The patient could be genetically diagnosed with bile salt export pump disease of PFIC type 2 or BRIC type 2. Various clinical features are observed in PFIC or BRIC patients with ABCB11 mutation.
Takahashi
Atsushi
A
Department of General Surgical Science (Surgery I), Gunma University, Graduate School of Medicine, Gunma, Japan. takaatsu@med.gunma-u.ac.jp
Hasegawa
Makoto
M
Sumazaki
Ryo
R
Suzuki
Makoto
M
Toki
Fumiaki
F
Suehiro
Taketoshi
T
Onigata
Kazumichi
K
Tomomasa
Takeshi
T
Suzuki
Tomoko
T
Matsui
Akira
A
Morikawa
Akihiro
A
Kuwano
Hiroyuki
H
D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D001647:Bile Acids and Salts / Q000097:blood; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D002780:Cholestasis, Intrahepatic / Q000151:congenital / Q000235:genetics* / Q000378:metabolism; D005500:Follow-Up Studies; D006471:Gastrointestinal Hemorrhage / Q000188:drug therapy; D013006:Growth Hormone / Q000172:deficiency / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D008099:Liver / Q000378:metabolism*; D008297:Male; D020125:Mutation, Missense; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*; D014812:Vitamin K / Q000627:therapeutic use
C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D001647:Bile Acids and Salts; D002756:Cholagogues and Choleretics; D014812:Vitamin K; D014580:Ursodeoxycholic Acid; D013006:Growth Hormone