兒童之肝內膽汁滯留及BSEP基因分析
Date Issued
2000
Date
2000
Author(s)
陳慧玲
DOI
892314B002040
Abstract
Background/Aim: Genetic defects of FIC1
and BSEP have recently been found to cause
progressive familial intrahepatic cholestasis
(PFIC). Mutations in both genes have not
been reported in Asian children, and the roles
of these genetic disorders in non-familial
infantile cholestasis are unclear. This study is
to elucidate the role of FIC1 and BSEP
mutations in children with infantile onset
chronic cholestasis in Taiwan.
Methods and Results: We examed 301
children admitted for intrahepatic cholestasis
during 1980 to 1999 in Taiwan. Fifty-two
had chronic intrahepatic cholestasis,
including 18 with Alagille syndrome, 2 with
neonatal Dubin-Johnson syndrome, 1 with
tyrosinemia, and 31 of unknown etiology.
These 31 patients were sub-grouped
according to g-glutamyltranspeptidase (GGT)
levels: low GGT (18 cases), high GGT (8
cases), and unknown GGT levels (5 cases).
Inborn errors of bile acid synthesis were
identified in four patients by serum bile acid
analysis. In the low GGT patients, two
distinct phenotypes could be defined: group 1
(5 patients) was characterized by bland
cholestasis and group 2 (8 patients) by giant
cell transformations. Group 2 patients were
associated with higher transaminase levels,
α -fetoprotein levels, and early mortality
(p=0.02). Reverse transcription-polymerase
chain reaction and cDNA sequencing were
performed in 7 infants with low GGT levels
for mutation analyses of FIC1 and BSEP
genes. FIC1 mutations were found in all 4
patients in group 1 but none in the 3 patients
in group 2. Whereas BSEP mutations were
found in 2 of the 3 patients in group 2. The
FIC1 mutations comprised of two deletions
and three missense mutations. The BSEP
mutations included two missense mutations
and 1 deletion. All the mutations were novel.
Conclusion: FIC1, BSEP mutations and
inborn errors of bile acid synthesis are
important etiologies in infants with nonfamilial
chronic intrahepatic cholestasis in
Taiwan. Combination of serum GGT, AFP
levels and histology is useful in
differentiating patients of FIC1 from BSEP
2
mutation, and the phenotype strongly
correlated with genetic diagnosis and
prognosis.
Subjects
cholestasis
gene mutation
childhood liver disease
Publisher
臺北市：國立臺灣大學醫學院小兒科
Type
report
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