Investigations
1st investigations to order
serum total bilirubin
Test
Normal total bilirubin measurements range from 5 to 21 micromol/L (0.3 to 1.2 mg/dL).
In RS, levels can range from 34 to 86 micromol/L (2 to 5 mg/dL), but occasionally may reach 340 micromol/L (20 mg/dL).
Result
elevated
serum conjugated bilirubin
Test
Normal serum conjugated bilirubin measurements range from 1.7 to 5.1 micromol/L (0.1 to 0.3 mg/dL).
In RS, >50% serum bilirubin will be conjugated.[4]
Result
elevated
urinary bilirubin
Test
Bilirubinuria is typically present.[4]
Result
elevated
serum aminotransferases, alkaline phosphatase, and gamma-GT
Test
Typically, LFT (serum aminotransferases, alkaline phosphatase, and gamma-GT) is normal, although occasional mild elevations may be seen.
Result
usually normal or mildly elevated
haemoglobin
Test
To differentiate from haemolytic anaemia, there will be no evidence of haemolysis.
Result
normal
absolute reticulocyte count
Test
To differentiate from haemolytic anaemia, there will be no evidence of haemolysis.
Result
normal
blood smear
Test
To differentiate from haemolytic anaemia, there will be no evidence of haemolysis.
Result
normal
plasma haptoglobin
Test
To differentiate from haemolytic anaemia, there will be no evidence of haemolysis.
Result
normal
Investigations to consider
serum bile acids (total)
Test
Serum fasting and postprandial bile acid concentrations will be normal.[4]
Normal values range from 0.73 to 5.63 micromol/L (0.3 to 2.3 micrograms/mL).
Result
normal
urinary coproporphyrins
Test
Total urinary coproporphyrin excretion is increased 2.5- to 5-fold in RS patients compared with healthy controls.
While coproporphyrin excretion is elevated in both RS and Dubin-Johnson syndrome (DJS), the proportion of coproporphyrin I to coproporphyrin III differs between the 2 conditions.
In RS, approximately 65% of the total coproporphyrin is excreted as coproporphyrin I, and in DJS, >80% is excreted as coproporphyrin I.[4]
Result
elevated
liver biopsy
Test
Because RS is mainly a diagnosis of exclusion, it is important to demonstrate a normal liver histology thereby excluding other more serious liver conditions.
Typically normal and parenchymal deposition of pigment is not seen.[4]
Result
normal
ultrasound of the liver and biliary tree
Test
Helps to exclude obstructive lesions in the visible bile ducts.
Result
normal
oral cholecystogram
Test
Used to differentiate from DJS.
In RS, the gall bladder is usually visualised on an oral cholecystogram.[4]
Result
gall bladder visualised
cholescintigraphy with 99mTc-HIDA
Test
Used when the diagnosis is equivocal.
Shows an absent or very faint uptake and prolonged visualisation of the cardiac pool.[20]
The pattern is not different from that seen in patients with hepatocellular disease and markedly elevated bilirubin levels. However, combined with clinical information and laboratory findings, it may be helpful in diagnosing RS.[20][21]
Result
absent or faint uptake of dye
molecular genetic testing
Test
May be considered when cholescintigraphy is not available or not recommended.[19]
Tests include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
Bi-allelic pathogenic variants in SLCO1B1 and SLCO1B3 confirm the diagnosis.[10][18][19]
Result
positive for deleterious gene mutations
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