Kembara Xtra - Medicine - Gilbert Syndrome

Kembara Xtra - Medicine - Gilbert Syndrome 
A benign hereditary disorder where there is no liver disease or hemolysis but there is mild, intermittent unconjugated hyperbilirubinemia
Child Safety Considerations
It is uncommon for the condition to be identified before puberty
pregnant women's issues
Morning sickness may cause some relative fasting, which might cause bilirubin levels to rise.

Epidemiology Predominant sex: male > female (2 to 7:1) Predominant age: present from birth but most frequently manifests in the second or third decade of life
Prevalence
8% of the population in the United States has the disease, yet only one in three people with it are aware of it.


Pathophysiology and Etiology 

Gilbert syndrome (GS) causes indirect hyperbilirubinemia because of poor hepatic bilirubin clearance (30% of normal), which is brought on by low levels of the enzyme uridine diphosphoglucuronate-glucuronosyltransferase (UDPGT).
Thus, there is a reduction in hepatic bilirubin conjugation (glucuronidation), albeit this may not be the only issue.

Genetics – Reduced conjugation of bilirubin with glucuronic acid results from hereditary abnormalities in the promoter region of the gene encoding the enzyme UDPGT. – Previously assumed to be an autosomal dominant disorder, GS is now believed to be inherited in an autosomal recessive manner.

Male gender, family history, and first-degree relatives are risk factors.


Accompanying Conditions 
S
GS is a hereditary condition that falls under the same spectrum as types I and II of Crigler-Najjar syndrome. But in these situations, bilirubin levels will be greater than 6 mg/dL.

The presence of stresses such fasting, dehydration, infection, lack of sleep, physical exercise, or surgery might result in a nonpruritic jaundice in GS patients. Some drugs may also provoke episodes of jaundice in people with GS due to aberrant metabolism. Other symptoms that may appear during an episode of jaundice, like exhaustion, are caused by the triggering factor and are not directly a result of GS. These include glucuronyl transferase inhibitors (such as gemfibrozil) and selective protease inhibitors (such as atazanavir and indinavir). There is some proof that the medications ribavirin, an antiviral used to treat hepatitis C, and tocilizumab, a monoclonal antibody used to treat rheumatoid arthritis, may also cause jaundice (4). Notably, there is no evidence linking the aforementioned medications to liver toxicity in GS patients.

clinical assessment 

the aforementioned factors (fasting, dehydration, infection, lack of sleep, physical exercise, surgery, and some drugs) may occasionally cause moderate jaundice. Exam should be free of signs of chronic liver disease stigma.

Hemolysis, ineffective erythropoiesis (megaloblastic anemias, some porphyrias, thalassemia major, sideroblastic anemia, severe lead poisoning, congenital dyserythropoietic anemias), cirrhosis, chronic persistent hepatitis, pancreatitis, biliary tract illness, and other conditions are among the differential diagnoses.

Initial test results from the laboratory and imaging
Bilirubin: high but less than 6 mg/dL (103 mol/L) and typically less than 3 mg/dL (51 mol/L), almost entirely indirect, with conjugated bilirubin within the normal range or less than 20% of the total bilirubin.

A normal CBC includes a peripheral smear.
The haptoglobin, lactate dehydrogenase, and reticulocyte count are all within normal limits.
Aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase, and -glutamyl transpeptidase (GGT) liver function tests are normal.
Direct Coombs testing is appropriate.
Up to 60% of GS patients have a minor hemolysis that is clinically inconsequential and frequently cannot be identified without complex red cell survival investigations.

Drugs that could affect lab findings include phenobarbital and nicotinic acid, which can both boost and lower bilirubin levels.

Disorders that could affect test findings include: Bilirubin levels rise when fasting and may rise when suffering from a feverish illness.


Tests in the Future & Special Considerations
If unconjugated hyperbilirubinemia persists in the absence of hemolysis or other liver disease, GS should be considered. If the exam and diagnostic workup are otherwise normal, a conclusive diagnosis may be recorded three to twelve months following the first diagnosis.
Diagnostic procedures and other testing are frequently not required.
A 48-hour fast is unworkable and irrelevant for GS.

If there is severe diagnostic uncertainty, provocation testing with rifampin may be used: - After 12 hours of fasting, an increase in total bilirubin to >1.9 mg/dL 2 hours after an oral dosage of rifampin 900 mg separates patients with GS with 100% sensitivity and 100% specificity.

For DNA mutations in the UGT1A1 gene, genetic testing is available as DNA-fragment sequencing or polymerase chain reaction (PCR).

Caution 
In most cases, excluding other diseases does not require a liver biopsy, barring the presence of concurrent liver illness.

Outpatient management is recommended; avoid pointless tests and procedures; and no specific treatment is required.

Patient Follow-Up Monitoring
There is no need for additional monitoring once GS has been positively identified.

Reassure them that GS is benign, and inform them of typical causes of jaundice.
Encourage them to share their diagnoses with their doctors.
 Inform patients to seek medical attention if they have severe or protracted jaundice as these could be symptoms of a different disease process.
GS is a benign condition with a great prognosis, and patients with it are eligible to donate their right liver lobes for transplantation.
According to preliminary research, people with GS may be more resistant to cardiovascular disease, type 2 diabetes, some malignancies such Hodgkin lymphoma, and overall mortality.

Complication
The GS has no reported complication

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