How is Gilbert Syndrome Diagnosed?
Gilbert syndrome is a benign hereditary condition causing hyperbilirubinemia. It is also known as familial non-hemolytic jaundice and constitutional hepatic dysfunction. It is caused due to mutations in promoter gene for UGT (uridine diphosphate glucuronyl transferase) enzyme, which is responsible for metabolism of bilirubin. Generally, Gilbert syndrome does not present any symptoms, except for mild jaundice (yellowing of eyes and skin).
How is Gilbert Syndrome Diagnosed?
In general, this condition is diagnosed inadvertently on routine blood tests, detected around 20 to 30 years of age. The people suffering from this condition are unaware of it until they are diagnosed with it, although the condition does not hamper their lives. However, mild and prolonged jaundice is a subject of anxiety for some patients and they may seek diagnosis in fear of a severe liver disorder. A confirmed diagnosis of Gilbert syndrome includes:
Medical History: A complete medical history of the individual is taken along with past medical history of jaundice, family history of Gilbert syndrome along with medication history.
Physical Examination: The individual is examined thoroughly in the abdomen along with detection of jaundice in the eyes, skin and oral mucosa.
Complete Blood Count: The first step is ordering routine blood count, which is usually normal in cases of Gilbert syndrome. CBC is done to rule out any infections that may elevate white blood cell count. For Gilbert syndrome, reticulocyte count is examined, which on maturation become red blood cells. In jaundice, the reticulocyte count is elevated due to increased breakdown of red blood cells (hemolytic anemia) leading to increased production of bilirubin, whereas in Gilbert syndrome they are normal.
Liver Function Test: They are ordered to check for any liver enzyme abnormality. These include ALT (Alanine transaminase), AST (Aspartate transaminase) and lactate dehydrogenase enzymes. If they are all normal and there is an elevation in unconjugated bilirubin, then Gilbert syndrome is suspected. Generally, in Gilbert syndrome cases, the serum bilirubin is found to be less than 6 mg/dl. The mean values are higher in men than females. Bilirubin levels can fluctuate, they can be normal in some Gilbert syndrome cases, whereas they can be elevated if a person is fasting, ill, stressed whether physically or emotionally, menstruating (women), making definitive diagnosis difficult. Nicotinic acid test is suggested for the diagnosis of Gilbert syndrome in which there is a significant rise in unconjugated bilirubin; however, this test is non-specific as unconjugated bilirubin can also rise in chronic liver disease, thus not making a definitive diagnosis.
Urine Tests: Urinalysis will show the lower levels of urobilinogen.
Immunohistochemical Assay: This uses polyclonal antibodies against UDP-glucuronosyltransferase enzyme. Staining of normal liver with specific dyes shows presence of UGT in all parts of the liver, especially higher concentrations in zone 3 that is responsible for excretion of bile acids. In Gilbert syndrome, the staining is low for UGT all over the liver and a faint stain is detected in zone 3 that confirms low levels of UGT.
Liver Biopsy: This involves taking a sample of liver tissue and examining it under a microscope to look for pathological changes in the liver tissue. Although, liver biopsy is not required in cases of Gilbert syndrome, it can be undertaken in cases that are difficult to diagnose and that require exclusion of other liver conditions.
Genetic Testing: Although Gilbert syndrome is caused due to mutation of gene that is responsible for coding UGT enzyme, there are no specific genetic tests to confirm the diagnosis of the condition. Genetic tests looking at the UGT1A1 gene may be used in labs for confirming the condition; however, they are not recommended on routine basis.
Differential Diagnosis: Gilbert syndrome can be confused with Crigler-Najjar syndrome type I and type II along with Lucey-Driscoll syndrome, so they should be ruled out before making a definitive diagnosis.
Gilbert syndrome is a benign condition that does not require any treatment or long term medical attention. It has been noted that small doses of Phenobarbital reduces bilirubin levels to normal, until the drug effect lasts.