A 23-year-old man has had episodes of mildly yellow eyes since childhood, without itching or abdominal pain. Results: total bilirubin 92 µmol/L (5.4 mg/dL) and direct bilirubin 60 µmol/L (3.5 mg/dL); ALT, AST, ALP, GGT, albumin and INR normal; hemoglobin and reticulocyte count normal; urine bilirubin positive. Urine coproporphyrin: total excretion 4 times the upper reference limit, with isomer I making up 62% of it (about 25% in healthy adults). Ultrasound of the liver and bile ducts is normal. His younger sister has the same findings. The most likely diagnosis is:

Benign recurrent intrahepatic cholestasis

In an Abu Dhabi hospital, a male term newborn becomes jaundiced at 30 hours. Total bilirubin is 245 µmol/L (14.3 mg/dL), almost all unconjugated. Mother and baby are both group O RhD positive, the DAT is negative, and the film shows a few bite cells and no spherocytes. Which test is most useful next?

Quantitative G6PD activity assay

Hemoglobin electrophoresis by HPLC

EMA binding test for spherocytosis

Repeat DAT with monospecific anti-IgG

In a newborn, jaundice is regarded as pathological rather than physiological when it first appears:

Within the first 24 hours of life

On the second or third day of life

Around day 5, when levels usually peak

Bilirubin metabolism and jaundice

19 DOH Abu Dhabi (HAAD) lab licensing practice questions on Bilirubin metabolism and jaundice, part of Clinical Chemistry. The first 19 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

Question 1 · Hard
A 23-year-old man has had episodes of mildly yellow eyes since childhood, without itching or abdominal pain. Results: total bilirubin 92 µmol/L (5.4 mg/dL) and direct bilirubin 60 µmol/L (3.5 mg/dL); ALT, AST, ALP, GGT, albumin and INR normal; hemoglobin and reticulocyte count normal; urine bilirubin positive. Urine coproporphyrin: total excretion 4 times the upper reference limit, with isomer I making up 62% of it (about 25% in healthy adults). Ultrasound of the liver and bile ducts is normal. His younger sister has the same findings. The most likely diagnosis is:
1. ADubin-Johnson syndrome
2. BBenign recurrent intrahepatic cholestasis
3. CGilbert syndrome
4. DRotor syndrome
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Answer: D · Rotor syndrome
Indirect bilirubin is 92 − 60 = 32 µmol/L, so about two thirds of the bilirubin is conjugated, and bilirubin in the urine confirms a conjugated hyperbilirubinemia. Normal enzymes, bile ducts and synthetic function, with no hemolysis, point to an inherited defect in bilirubin handling rather than liver disease. Of the two conjugated forms, Rotor syndrome raises total urine coproporphyrin several-fold with isomer I below 80%, as here; Dubin-Johnson syndrome has a normal total with more than 80% isomer I and a darkly pigmented liver. Gilbert syndrome raises only unconjugated bilirubin, and benign recurrent intrahepatic cholestasis causes itchy attacks with a raised ALP. Both Rotor and Dubin-Johnson syndromes are benign and need no treatment.
- A: Dubin-Johnson gives a normal total coproporphyrin with more than 80% isomer I.
- B: This causes itchy attacks with a raised ALP, which are absent here.
- C: Gilbert syndrome raises unconjugated bilirubin; here most of it is conjugated.
Question 2 · Hard
A 9-day-old term boy, fed a standard milk formula since birth, is admitted with poor feeding, vomiting, lethargy and jaundice. His liver is enlarged and his blood culture grows Escherichia coli. Results: total bilirubin 285 µmol/L (16.7 mg/dL), direct bilirubin 92 µmol/L (5.4 mg/dL), ALT 140 U/L, INR 2.0 and glucose 2.6 mmol/L (47 mg/dL). His urine is positive for reducing substances by copper reduction but negative on the glucose oxidase strip. The DAT is negative, the blood film shows no bite cells or spherocytes, and he has never been transfused. Which test should be done next?
1. ARed cell G6PD activity
2. BRed cell GALT enzyme activity
3. CSerum TSH and free T4
4. DAlpha-1 antitrypsin phenotype
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Answer: B · Red cell GALT enzyme activity
Indirect bilirubin is 285 − 92 = 193 µmol/L, and the direct fraction is about a third of the total, so this is not physiological jaundice but liver dysfunction with a conjugated component. Liver injury, coagulopathy and E. coli sepsis in a milk-fed newborn, with a non-glucose reducing sugar in the urine, is the classic picture of galactosemia. Red cell galactose-1-phosphate uridyltransferase (GALT) activity confirms classic galactosemia, and lactose should be stopped at once while the result is awaited. The test needs a sample taken before any transfusion, because donor red cells give a falsely normal result. G6PD deficiency and hypothyroidism cause mainly unconjugated jaundice without a urinary reducing sugar, and alpha-1 antitrypsin deficiency causes cholestasis without galactosuria.
- A: G6PD deficiency gives unconjugated jaundice from hemolysis, with no urinary reducing sugar.
- C: Hypothyroidism prolongs unconjugated jaundice and does not cause galactosuria or sepsis.
- D: Alpha-1 antitrypsin deficiency causes cholestasis but not a urinary reducing sugar.
Question 3 · Hard
In an Abu Dhabi hospital, a male term newborn becomes jaundiced at 30 hours. Total bilirubin is 245 µmol/L (14.3 mg/dL), almost all unconjugated. Mother and baby are both group O RhD positive, the DAT is negative, and the film shows a few bite cells and no spherocytes. Which test is most useful next?
1. AHemoglobin electrophoresis by HPLC
2. BEMA binding test for spherocytosis
3. CRepeat DAT with monospecific anti-IgG
4. DQuantitative G6PD activity assay
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Answer: D · Quantitative G6PD activity assay
Early jaundice in a DAT-negative boy with bite cells suggests oxidant hemolysis from G6PD deficiency, an X-linked disorder common in the UAE and the Gulf. A quantitative G6PD assay confirms it. Results can be falsely normal soon after hemolysis, when young red cells with more enzyme dominate, so a borderline result is repeated later. The family is advised to avoid fava beans and oxidant drugs.
- A: Beta-chain hemoglobin disorders rarely cause hemolysis at birth, when HbF predominates.
- B: There are no spherocytes, and bite cells point to oxidant damage, not a membrane defect.
- C: With no ABO or D incompatibility and a negative DAT, antibody hemolysis is unlikely.
Question 4 · Easy
In Crigler-Najjar syndrome type 1, hepatic bilirubin UDP-glucuronosyltransferase (UGT1A1) activity is:
1. AAbout 30% of normal
2. BAbout 10% of normal
3. CAbsent or almost absent
4. DNormal, with an export defect
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Answer: C · Absent or almost absent
Type 1 has no functional UGT1A1, so bilirubin cannot be conjugated. Unconjugated bilirubin is usually above 340 µmol/L (20 mg/dL) from the first days of life, with a high risk of kernicterus. Phenobarbital has no effect because there is no enzyme to induce. Treatment is long daily phototherapy and, finally, liver transplantation.
- A: About 30% of normal activity is typical of Gilbert syndrome.
- B: Residual activity below about 10% is type 2 (Arias syndrome).
- D: Normal conjugation with an export defect describes Dubin-Johnson syndrome.
Question 5 · Easy
In a newborn, jaundice is regarded as pathological rather than physiological when it first appears:
1. ADuring the fourth day of life
2. BWithin the first 24 hours of life
3. COn the second or third day of life
4. DAround day 5, when levels usually peak
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Answer: B · Within the first 24 hours of life
Physiological jaundice appears after the first 24 hours, peaks around days 3 to 5 in term babies and fades within about 2 weeks. Jaundice in the first day suggests hemolysis (Rh or ABO disease, G6PD deficiency, spherocytosis) or infection. These babies need a serum bilirubin at once, with blood group, DAT and a conjugated fraction. Early onset is one of the strongest risk factors for severe hyperbilirubinemia.
- A: Jaundice on day 4 falls within the physiological pattern.
- C: Days 2 to 3 are the usual onset of physiological jaundice.
- D: Day 3 to 5 is when physiological jaundice normally peaks.
Question 6 · Medium
One reason healthy term newborns develop transient unconjugated hyperbilirubinemia is:
1. ALittle beta-glucuronidase in the newborn gut
2. BRed cell survival longer than in adults
3. CLow hepatic UGT1A1 activity in the first days
4. DFast conversion of bilirubin to urobilinogen
Answer and explanation in LearnFree account
Question 7 · Hard
A dry-slide analyzer reports these bilirubin fractions for an adult recovering from biliary obstruction: total 150 µmol/L, unconjugated (Bu) 30 µmol/L and conjugated (Bc) 70 µmol/L. What is the delta (albumin-bound) bilirubin?
1. A80 µmol/L
2. B120 µmol/L
3. C50 µmol/L
4. D40 µmol/L
Answer and explanation in LearnFree account
Question 8 · Medium
In Dubin-Johnson syndrome, the urinary coproporphyrin pattern is typically:
1. AMarkedly raised total, mostly isomer III
2. BNormal total, with over 80% as isomer I
3. CNormal total, with about 75% as isomer III
4. DRaised total, with about 65% as isomer I
Answer and explanation in LearnFree account
Question 9 · Medium
A 4-day-old exclusively breastfed term baby has lost 11% of birth weight and has few wet nappies. Total bilirubin is 290 µmol/L (17.0 mg/dL) and direct bilirubin 10 µmol/L (0.6 mg/dL); the DAT is negative and the hemoglobin and blood film are normal. What is the most likely cause?
1. AExtrahepatic biliary atresia
2. BCrigler-Najjar syndrome type 1
3. CSuboptimal milk intake (breastfeeding jaundice)
4. DBreast milk jaundice from a factor in the milk
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Question 10 · Medium
An adult has total bilirubin 52 µmol/L (3.0 mg/dL) and direct bilirubin 44 µmol/L (2.6 mg/dL). What is the indirect bilirubin, and what type of hyperbilirubinemia is this?
1. A96 µmol/L; mainly conjugated
2. B44 µmol/L; mainly conjugated
3. C8 µmol/L; mainly conjugated
4. D8 µmol/L; mainly unconjugated
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Question 11 · Medium
Rotor syndrome causes conjugated hyperbilirubinemia because of a defect in:
1. ABilirubin conjugation by the enzyme UGT1A1
2. BCanalicular export by the MRP2 transporter
3. CHepatic reuptake by OATP1B1 and OATP1B3
4. DBile flow through the intrahepatic ducts
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Question 12 · Hard
A 3-week-old has persistent jaundice, constipation, poor feeding, a large tongue and an umbilical hernia. Total bilirubin is 230 µmol/L (13.5 mg/dL), direct 9 µmol/L (0.5 mg/dL); the DAT is negative and hemoglobin is normal. The newborn screening result has not been received. Which test should be done next?
1. AUrine reducing substances
2. BG6PD activity
3. CHemoglobin electrophoresis
4. DTSH and free T4
Answer and explanation in LearnFree account
Question 13 · Hard
A 2-week-old breastfed baby is still jaundiced. Total bilirubin is 150 µmol/L (8.8 mg/dL) and direct bilirubin 45 µmol/L (2.6 mg/dL). The laboratory flags a direct bilirubin above 17 µmol/L (1.0 mg/dL) as abnormal in infants. The correct interpretation is:
1. AConjugated hyperbilirubinemia needing urgent evaluation
2. BPhysiological jaundice that needs no further tests
3. CBreast milk jaundice; continue feeding unchanged
4. DUnconjugated jaundice needing phototherapy alone
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Question 14 · Hard
A 45-year-old man starts irinotecan for colon cancer and develops severe neutropenia and diarrhea after the first dose. Past results show total bilirubin 30-45 µmol/L (1.8-2.6 mg/dL), almost all unconjugated, with normal liver enzymes and no hemolysis. The inherited condition that best explains his toxicity is:
1. ACrigler-Najjar syndrome type 1
2. BRotor syndrome (SLCO1B1/1B3 loss)
3. CDubin-Johnson syndrome (ABCC2 variants)
4. DGilbert syndrome (UGT1A1*28 homozygosity)
Answer and explanation in LearnFree account
Question 15 · Medium
A newborn has been under phototherapy for 12 hours. Transcutaneous bilirubin reads 150 µmol/L, while serum bilirubin drawn at the same moment is 260 µmol/L. What best explains the gap?
1. APhototherapy has bleached the bilirubin in the skin
2. BThe serum result includes delta bilirubin
3. CThe serum sample was exposed to light before testing
4. DThe infant's dark skin made the meter read low
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Question 16 · Medium
A term baby born by vacuum delivery has a large cephalhematoma. On day 3 unconjugated bilirubin is rising; the DAT is negative and hemoglobin is normal. The extra bilirubin comes mainly from:
1. AReduced albumin binding of bilirubin
2. BBreakdown of red cells in the hematoma
3. CImpaired canalicular excretion
4. DMaternal antibody coating the red cells
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Question 17 · Easy
Which two inherited disorders cause a mainly conjugated (direct) hyperbilirubinemia?
1. ADubin-Johnson and Rotor syndromes
2. BGilbert and Crigler-Najjar syndromes
3. CGilbert and Rotor syndromes
4. DCrigler-Najjar types 1 and 2
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Question 18 · Hard
A 5-day-old has total bilirubin 248 µmol/L and direct bilirubin 14 µmol/L. The doctor asks for the indirect bilirubin in mg/dL (1 mg/dL = 17.1 µmol/L). What should be reported?
1. A13.7 mg/dL
2. B14.5 mg/dL
3. C15.3 mg/dL
4. D0.8 mg/dL
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Question 19 · Hard
A 7-year-old has had unconjugated hyperbilirubinemia since birth. Total bilirubin is 160 µmol/L (9.4 mg/dL), direct 7 µmol/L; liver enzymes, hemoglobin and reticulocytes are normal. After two weeks of phenobarbital, total bilirubin falls to 70 µmol/L (4.1 mg/dL). The most likely diagnosis is:
1. ACrigler-Najjar syndrome type 1
2. BCrigler-Najjar syndrome type 2
3. CGilbert syndrome
4. DDubin-Johnson syndrome
Answer and explanation in LearnFree account

Bilirubin metabolism and jaundice

In Crigler-Najjar syndrome type 1, hepatic bilirubin UDP-glucuronosyltransferase (UGT1A1) activity is:

In a newborn, jaundice is regarded as pathological rather than physiological when it first appears:

One reason healthy term newborns develop transient unconjugated hyperbilirubinemia is:

A dry-slide analyzer reports these bilirubin fractions for an adult recovering from biliary obstruction: total 150 µmol/L, unconjugated (Bu) 30 µmol/L and conjugated (Bc) 70 µmol/L. What is the delta (albumin-bound) bilirubin?

In Dubin-Johnson syndrome, the urinary coproporphyrin pattern is typically:

A 4-day-old exclusively breastfed term baby has lost 11% of birth weight and has few wet nappies. Total bilirubin is 290 µmol/L (17.0 mg/dL) and direct bilirubin 10 µmol/L (0.6 mg/dL); the DAT is negative and the hemoglobin and blood film are normal. What is the most likely cause?

An adult has total bilirubin 52 µmol/L (3.0 mg/dL) and direct bilirubin 44 µmol/L (2.6 mg/dL). What is the indirect bilirubin, and what type of hyperbilirubinemia is this?

Rotor syndrome causes conjugated hyperbilirubinemia because of a defect in:

A 2-week-old breastfed baby is still jaundiced. Total bilirubin is 150 µmol/L (8.8 mg/dL) and direct bilirubin 45 µmol/L (2.6 mg/dL). The laboratory flags a direct bilirubin above 17 µmol/L (1.0 mg/dL) as abnormal in infants. The correct interpretation is:

A newborn has been under phototherapy for 12 hours. Transcutaneous bilirubin reads 150 µmol/L, while serum bilirubin drawn at the same moment is 260 µmol/L. What best explains the gap?

A term baby born by vacuum delivery has a large cephalhematoma. On day 3 unconjugated bilirubin is rising; the DAT is negative and hemoglobin is normal. The extra bilirubin comes mainly from:

Which two inherited disorders cause a mainly conjugated (direct) hyperbilirubinemia?

A 5-day-old has total bilirubin 248 µmol/L and direct bilirubin 14 µmol/L. The doctor asks for the indirect bilirubin in mg/dL (1 mg/dL = 17.1 µmol/L). What should be reported?

A 7-year-old has had unconjugated hyperbilirubinemia since birth. Total bilirubin is 160 µmol/L (9.4 mg/dL), direct 7 µmol/L; liver enzymes, hemoglobin and reticulocytes are normal. After two weeks of phenobarbital, total bilirubin falls to 70 µmol/L (4.1 mg/dL). The most likely diagnosis is: