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GILBERT'S SYNDROME - a patient's guide
Dr Philip Wong - Gastroenterologist and Hepatologist
Gilbert's Syndrome
Gilbert's syndrome is a common inherited disorder that
affects the processing by the liver of the pigments in the
bile called bilirubin. This results in an increase in the
level of bilirubin levels in the bloodstream and can lead
to a yellowing of the skin and the eyes, that is jaundice.
The liver itself is otherwise normal and people with Gilbert's
syndrome have a normal life expectancy. It is common and
not a dangerous condition in any way.
Enzyme Defect
Gilbert's syndrome is arguably the most common medical
syndrome identified. In normal people bilirubin is bound
(conjugated) to specific protein(s) by a liver enzyme, called
bilirubin-uridine glucuronosyltransferase (bilirubin-UGT),
which allows it to be excreted in the bile. It has long
been recognised that bilirubin-UGT activity measured in
liver biopsies of individuals with Gilbert's syndrome is
almost invariably reduced, suggesting that reduced enzyme
activity is the source of the impairment in bilirubin metabolism.
Thus in Gilbert's syndrome bilirubin is less efficiently
excreted into the bile leading to elevated levels of unconjugated
bilirubin in the bloodstream.
Clinical and laboratory findings
Gilbert's syndrome is most often recognised in the second
or third decade of life and is rarely diagnosed before puberty.
The diagnosis is made most often following routine screening
blood tests or when fasting associated with surgery or intercurrent
illness unmasks the hyperbilirubinemia. Gilbert's syndrome
affects 3 to 7% of the population, with males predominating
over females by a ratio of 2-7:1.
The normal bilirubin level in the blood is less than 20
umol/L while in Gilbert's syndrome the bilirubin level is
usually mildly raised. In most cases is less than 50 umol/L
and is always less than 100 umol/L. There is considerable
daily and seasonal fluctuation. The bilirubin may be normal
on occasion in up to one-third of patients.
Because the liver is otherwise normal in individuals with
Gilbert's syndrome, physical examination is normal apart
from the occasional presence of jaundice. At least 30% of
patients with Gilbert's syndrome are asymptomatic, apart
from the presence of mild jaundice, and are unaware of the
abnormality until it is detected by incidental laboratory
examination or in the course of family studies. Some people
may experience a variety of nonspecific and varied symptoms,
including vague abdominal discomfort, fatigue, or malaise
In general, these symptoms do not correlate with the plasma
bilirubin level and are more likely related to anxiety rather
than to the underlying disorder in metabolism. In a third
group of patients, hyperbilirubinemia may be unmasked during
fasting, which usually produces an increase in the plasma
unconjugated bilirubin level. Thus, sub clinical individuals
may first be detected in association with caloric withdrawal
due to an intercurrent febrile illness, "morning sickness"
of pregnancy or postoperatively.
Diagnosis and Treatment
The diagnosis of Gilbert's syndrome is suggested by the
clinical finding of mild chronic unconjugated hyperbilirubinemia.
A family history should be sought and clinical evidence
of other liver or blood disorders, including haemolysis
(abnormal breakdown of red cells) excluded. Further confirmation
of the diagnosis may be achieved by determining the effect
of fasting or intravenous nicotinic acid administration
on the blood bilirubin concentration. Either manipulation
generally results in a two- to threefold rise in plasma
bilirubin level, even if the initial bilirubin concentrations
are normal. However, not all patients with Gilbert's syndrome
respond to these tests, which appear less sensitive and
specific for females than males. Other diagnostic manoeuvres
that have been advocated are measurement of the effect of
phenobarbital on plasma bilirubin concentration, and the
administration of a tracer dose of radiolabeled bilirubin
for estimation of the percentage of the dose remaining in
the plasma after 4 hours.
Given the above considerations, a presumptive diagnosis
of Gilbert's syndrome can be made in an essentially asymptomatic
individual if he /she has (1) unconjugated hyperbilirubinemia
on several occasions; (2) normal results of a complete blood
cell count, blood smear, and reticulocyte count; and (3)
normal liver enzyme tests (see article on liver function
tests) and (4) other disease processes have been excluded.
If no further laboratory abnormalities develop on two or
three follow-up tests during the next 12 to 18 months, then
the presumptive diagnosis becomes definitive. It is conceivable
that genetic testing may play a role in the diagnosis of
this condition in the future.
Once the diagnosis is established, the most important
aspect of management is to reassure the patient with regard
to the benign and inconsequential nature of the disorder
and the excellent prognosis and to prevent further unnecessary
investigations.
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