Tests
1st tests to order
unconjugated bilirubin
Test
Repeated measurements to document elevated levels 6 to 18 months after initial elevated level.
Result
elevated; usually <4 mg/dL and invariably <6 mg/dL
liver aminotransferases
Test
Repeated measurements after 6-18 months to ensure that levels remain normal. If repeat levels are elevated, workup for alternative causes is required.
Result
normal
gamma-glutamyl transpeptidase
Test
Repeated measurements after 6-18 months to ensure that levels remain normal. If repeat levels are elevated, workup for alternative causes is required.
Result
normal
lactate dehydrogenase
Test
Repeated measurements after 6-18 months to ensure that levels remain normal. If repeat levels are elevated, workup for alternative causes is required.
Result
normal
CBC
Test
Repeated measurements after 6-18 months to ensure that levels remain normal. If repeat levels are elevated, workup for alternative causes is required.
Result
normal
peripheral blood smear
Test
Repeated measurements after 6-18 months to ensure that results remain normal. If repeat results are abnormal, workup for alternative causes is required.
Result
normal
direct Coombs' test
Test
To exclude ABO or Rh isoimmunization as a cause of hemolytic anemia.
Result
negative
Tests to consider
liver biopsy
Test
Liver biopsy is not usually necessary. Performance of a liver biopsy is recommended only if persistent elevation of unconjugated bilirubin is otherwise unexplained, is symptomatic, is worsening over time, and/or associated with abnormal transaminases.[19]
Result
usually normal; may have an accumulation of a lipofuscin-like pigment around the terminal hepatic venules; may demonstrate features of coexisting liver disease if present
plasma unconjugated bilirubin response to fasting
Test
GS patients who consume a diet of ≤400 kcal/day will have a 2- to 3-fold rise in the plasma unconjugated bilirubin level within 48 hours of initiating the fast. The level should return to normal with the resumption of a normal diet. The same effect may be seen with a normal diet that is devoid of lipids. The bilirubin level again should normalize when lipids are restored in the diet. The mechanism of these processes is not entirely understood.[23]
Result
2- to 3-fold rise in plasma unconjugated bilirubin level on fasting if patient consumes a diet of ≤400 kcal/day, or a diet devoid of lipids, observed within 48 hours of initiating the fast; level should return to normal within 2 to 3 days upon resumption of a normal diet
plasma unconjugated bilirubin response to nicotinic acid
Test
Normal subjects, or those with hemolysis, have more modest or no increase in bilirubin level.[8] This test is rarely needed but may be of value in cases of diagnostic uncertainty, and in the further characterization of confirmed cases.
Result
2- to 3-fold rise in the plasma unconjugated bilirubin level within 3 hours after intravenous administration of nicotinic acid 50 mg
UGT1A1 genotyping
Test
Polymerase chain reaction can be used to identify mutations and genetic polymorphisms (e.g., UGT1A1*28) found in the TATA promoter region of the UGT1A1 gene.[20][21]
While not routinely used in the diagnostic workup of GS, this may be of value in cases of diagnostic uncertainty, and in the further characterization of confirmed cases. If there are existing genetic test results, do not perform repeat testing unless there is uncertainty about the existing result, e.g., the result is inconsistent with the patient’s clinical presentation or the test methodology has changed.[22]
Result
presence of mutation ± prognostic polymorphisms (e.g., UGT1A1*28)
UDPGT enzyme activity
Test
Although serum bilirubin concentrations act as an indirect measure of uridine-diphosphoglucuronate glucuronosyltransferase (UDPGT) activity, direct assays of UDPGT enzymatic activity can be performed.[21]
While not routinely used in the diagnostic workup of GS, this may be of value in cases of diagnostic uncertainty, and in the further characterization of confirmed cases.
Result
reduced activity
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