Transcript Gilbert syndrom

Research Center for Genetic Engineering and Biotechnology “Georgi D. Efremov”, MASA
Gilbert’s syndrome
What is Gilbert’s syndrome?
Gilbert’s Syndrome is an inherited form of unconjugated
hyperbilirubinaemia resulting in mild jaundice occurring in
the absence of haemolysis or other underlying liver disease.
Typically, total serum bilirubin concentration is between 20
and 50 μmol/L and may be noticeable within the sclera, skin
and mucous membranes.
The hyperbilirubinaemia is caused by reduced activity of the
hepatic 1A1 isoform of the uridine diphosphoglucose
glucuronosyltransferase enzyme (UGT1A1), which is
responsible for conjugating water insoluble unconjugated
bilirubin to glucuronic acid2.
It is most often detected during routine blood tests taken
during periods of fasting, infection, intense exercise and
after surgery.
Epidemiology
Gilbert's syndrome is a very common hereditary condition.
About 1 in 20 people has this syndrome - but 1 in 3 people
who have it will not be aware of it. It is more common in
men than in women. It is often first diagnosed in the late
teens or early twenties.
Genetics
The majority of cases of Gilbert’s Syndrome are caused by a
polymorphism in the promoter region of the UGT1A1 gene,
the A(TA)6TAA element2. The insertion of two extra
nucleotides (TA) within this TATA box results in a
A(TA)7TAA mutant allele, designated UGT1A1*28.
The UGT1A1*28 homozygous genotype is expressed as 7/7
(positive–Gilberts Syndrome)
A UGT1A1*28 heterozygous genotype is expressed as 6/7
(carrier)
A UGT1A1*28 wildtype is expressed as 6/6 (normal)
Since Gilberts Syndrome is autosomal recessive, carriers
(6/7 genotype) are not affected.
What are the symptoms of Gilbert's
syndrome?
Usually none. The level of bilirubin in the blood goes up and
down. However, this does not usually cause any problems
as the level does not go very high.
Jaundice. If the level of bilirubin goes above a certain level
you become jaundiced (yellowing of the skin and whites of
the eyes). This is because bilirubin is an orangy-yellow
colour. Some people with Gilbert's syndrome become mildly
jaundiced from time to time. This may seem alarming, but is
of little concern if the cause is Gilbert's syndrome. The
jaundice tends to occur most commonly if you are ill with
another problem such as an infection, starvation, repeated
vomiting, following surgery or during times of exertion or
stress.
What is the treatment for Gilbert's
syndrome?
No treatment is needed. People with Gilbert's syndrome
normally lead healthy lives. Life expectancy is not affected
and life insurance is not affected. Mild jaundice may recur
from time to time for short periods, but usually causes no
health problems.
Diagnosis
RCGEB
of
Gilbert's
syndrome
at
Diagnosis of Gilbert’s syndrome at RCGEB is based on
analysis of UGT1A1*28 mutation.
Material for testing
Full blood samples into sterile tubes with anticoagulant
EDTA
Genetics testing for Gilbert's syndrome
Price (МКД)
Detection of UGT1A1*28
7500
References
Bosma PJ, Chowdhury JR, Bakker C et al. The genetic basis of the reduced expression of bilirubin UDP- glucuronosyltransferase 1 in Gilberts
Syndrome. N Eng J Med. 1995. 338; 1171-1175.
RCGEB, 2013