A case report of Gilbert Syndrome

Abstract

Gilbert syndrome is benign, often familial condition characterized by recurrent but asymptomatic mild unconjugated hyperbilirubinemia in the absence of haemolysis or underlying liver disease. If, it becomes apparent, it is not until adolescence and then usually in association with stress such as intercurrent illness, fasting or strenuous exercise. Virtually all patients have decreased level of UDP-Glucuronosyltransferase, but there also is evidence for a defect in hepatic uptake of bilirubin as well. This case is reported due to its rarity. The prevalence of Gilbert syndrome in U.S is 3-7% of the population.

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Case Note
A case report of Gilbert Syndrome
Manandhar SR¹, Gurubacharya RL², Baral MR³, Manandhar DS
4
1
Medical officer,
2
Lecturer,
3
Professor,
4
Professor and HOD, Department of Paediatrics Kathmandu Medical College
Teaching Hospital
Abstract
Gilbert syndrome is benign, often familial condition characterized by recurrent but asymptomatic mild unconjugated
hyperbilirubinemia in the absence of haemolysis or underlying liver disease. If, it becomes apparent, it is not until
adolescence and then usually in association with stress such as intercurrent illness, fasting or strenuous exercise.
Virtually all patients have decreased level of UDP- Glucuronosyltransferase, but there also is evidence for a defect
in hepatic uptake of bilirubin as well. This case is reported due to its rarity. The prevalence of Gilbert syndrome in
U.S is 3-7% of the population.
Keywords: Gilbert Syndrome, familial non-haemolytic jaundice, hereditary non-haemolytic bilirubinaemia, low-
grade chronic hyperbilirubinemia
ugustine Gilbert and Pierre Lereboullet first
described Gilbert syndrome, the most common
inherited cause of unconjugated hyperbilirubinemia,
in 1901. Both autosomal recessive and autosomal
dominant patterns have been described. The
syndrome is characterized by intermittent jaundice in
the absence of haemolysis or underlying liver
disease. The hyperbilirubinemia is mild and by
definition < 6 mg/dl. However, most patients exhibit
levels of 3 mg/dl. Considerable daily and seasonal
variations are observed and bilirubin level
occasionally may be normal in as many as one -third
of patients.
Gilbert syndrome may be precipitated by
dehydration, fasting menstrual periods or stress, such
as an intercurrent illness or vigorous exercise.
Patients may complain of vague abdominal
discomfort and general fatigue for which no cause is
found. These episodes resolve spontaneously and no
treatment is required except for supportive care.
Case report
A 14 year old boy hailing from Bishal Nagar,
Kathmandu admitted in Paediatric ward KMCTH
with history of yellowish discolouration of sclera for
10 days. There were no other complaints. Urine
colour was normal. Child had history of similar
illness one year back and also 3 months back, which
subsided on its own. For present complaint, child was
shown to Ayurvedic doctor who advised restriction of
diet including fatty meals. However, mother noticed
the deepening of jaundice in sclera without any
abnormality in urine colour. On physical
examination, mild jaundice present, but no other
abnormal physical findings were evident.
Investigations done revealed normal haemoglobin,
total and differential count ESR and adequate
platelets. Reticulocyte was within normal limit
(0.5%). Peripheral blood picture showed no
abnormality including any features of haemolysis.
Osmotic fragility done was within normal limit. Liver
function tests were all within normal limit including
HBsAg and AntiHCV with the exception of
unconjugated hyperbilirubinemia on several
occasions.
The maximum total and indirect serum bilirubin
reached were 5.3mg/dl and 4.9mg/dl respectively.
Thus, keeping possibility of Gilbert syndrome, child
was subjected to further test, that is, fasting or
provocation test (child kept on 400Kcal/day for 48
hours). Results found as follows;
Before fasting:
Serum bilirubin Total-1.5 mg/dl
Indirect-0.75 mg/dl
After 48 hours of fasting:
Serum bilirubin: Total-3.61mg/dl
Indirect-2.16 mg/dl
Urine, stool and chest radiograph examinations done
all were within normal limits.
Correspondence:
Dr. Rajesh Lal Gurubacharya, Lecturer, Dept of Paediatrics,
KMCTH, Sinamangal, KTM.
E-mail: rajesh_pul@rediff.com/hotmail.com
A
Kathmandu University Medical Journal (2003) Vol. 1, No. 3, 187-189

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USG Abdomen was also normal.
Discussion
Unconjugated hyperbilirubinemia in Gilbert
syndrome has long been recognized as due to under
activity of the conjugating enzyme system Uridine
diphosphate glucuronosyltransferase (UDPGT).
Bilirubin UDPGT is responsible for conjugating
bilirubin into bilirubin monoglucuronides and
diglucuronides and is located primarily in the
endoplasmic reticulum of hepatocytes. The UGT1
gene locus for Gilbert syndrome is located on
chromosome 2 and is responsible for virtually all
bilirubin conjugation and UGT2 playing little, if any
role.
Gilbert syndrome is a benign condition with no
associated morbidity or mortality affecting all races
occurring predominantly in men with a male to
female ratio ranging from 2:1-7:1. It usually is
diagnosed around puberty, possibly due to inhibition
of bilirubin glucuronidation by endogenous steroid
hormones. In older subjects, the diagnosis is usually
made when unconjugated hyperbilirubinemia is noted
on routine blood tests or unmasked by an intercurrent
illness or stress.
Diagnosis of Gilbert syndrome can be made in the
presence of (1) unconjugated hyperbilirubinemia
noted on several occasions;(2) normal results on
CBC, reticulocyte count, and blood smear;(3) normal
liver function test results; and absence of other
disease processes. Additional tests are rarely required
for a diagnosis as it is straightforward. However,
following investigations are performed occasionally
to confirm a diagnosis of Gilbert syndrome.
• Fasting: This usually results in a 2- to 3- fold
rise in plasma unconjugated bilirubin within
48 hours of a fast that returns to normal levels
within 24 hours of resuming a normal diet.
Although unconjugated bilirubin levels also
rise with fasting in patients with haemolysis or
liver disease, the magnitude of the rise is less
than that observed with Gilbert syndrome. A
similar rise in plasma bilirubin also is
observed with normocaloric diets deficient in
lipids and reverse promptly with lipid
replacement.
• Nicotinic acid: Intravenous administration of
50 mg of nicotinic acid results in a 2-to3- fold
rise in plasma unconjugated
hyperbilirubinemia within 3 hours.
• Phenobarbital: Phenobarbital and other
enzyme inducers of the bilirubin-UDPGT
system will normalize plasma bilirubin in
patients with Gilbert syndrome.
• Rifampicin test: This test is popular because
of non-invasive in nature. It is as reliable as
fasting test. Per oral administration of 600-900
mg of rifampicin results in rise in plasma
unconjugated hyperbilirubinemia within 2-4
hours.
• Thin-layer chromatography: This test is
diagnostic for Gilbert syndrome when it shows
a significantly higher proportion of
unconjugated bilirubin when compared to
individuals with chronic haemolysis, liver
disease or those who are healthy. If
confirmation of the diagnosis is truly essential,
chromatographic determination is of potential
use. This will show an increased ratio of
bilirubin monoglucuronide to diglucuronide,
reflecting reduced bilirubin-UDPGT activity.
• Polymerase chain reaction: The polymerase
chain reaction (PCR) is a novel and rapid
method of identifying genetic polymorphisms
in the TATA box of the UDPGT1 gene using
fluorescence resonance energy transfer.
• Liver biopsy: It is not performed routinely and
is rarely necessary for a diagnosis. Liver is
normal histologically.
Conclusion
In the light of above case, if a child comes with
isolated unconjugated hyperbilirubinemia (< 6 mg/dl)
on several occasions in the absence of haemolysis or
underlying liver disease; Gilbert syndrome should be
entertained in the differential diagnosis of
unconjugated hyperbilirubinemia, being the most
common inherited cause. It has no deleterious
associations and an excellent prognosis, and those
who have it can lead a normal lifestyle.
Acknowledgement
Sincere thanks to Dr. I.L. Shrestha for kindly
performing fasting test and also to Department of
pathology KMCTH.
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Correspondence
Dr. Rajesh Lal Gurubacharya,Lecturer,Dept of Pediatrics,KMCTH
5. Sinamangal,KTM,rajesh_pul@rediff.com/hotmail.com