Gilbert-Lereboullet Syndrome

Gilbert-Lereboullet Syndrome: An Overview

Gilbert-Lereboullet syndrome (GLS), also known as Gilbert’s syndrome or familial non-hemolytic hyperbilirubinemia, is a common inherited condition that affects the liver. It is characterized by elevated levels of bilirubin in the blood, but without any signs of liver damage or dysfunction.

Epidemiology

GLS is the most common inherited liver disorder, affecting approximately 5-10% of the population worldwide. It is more prevalent in people of European descent and least common in people of African descent. Men and women are equally affected.

Etiology

GLS is caused by a mutation in the UGT1A1 gene, which encodes the enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1). This enzyme is responsible for adding glucuronic acid to bilirubin, which makes it more water-soluble and easier to excrete in bile.

In individuals with GLS, the UGT1A1 enzyme is partially deficient, leading to decreased glucuronidation of bilirubin. As a result, bilirubin accumulates in the blood, causing hyperbilirubinemia.

Clinical Features

The most common symptom of GLS is intermittent jaundice, which appears as a yellowing of the skin and whites of the eyes. The jaundice is usually mild and may be more noticeable during times of stress, such as illness, fasting, or dehydration.

Other symptoms of GLS may include:

• Fatigue
• Abdominal pain
• Nausea
• Vomiting
• Pruritus (itching)
• Dark urine
• Light-colored stools

Diagnosis

GLS is typically diagnosed based on:

• Clinical symptoms
• Blood tests showing elevated bilirubin levels
• Normal liver function tests (e.g., ALT, AST)
• Genetic testing to identify the UGT1A1 mutation

Differential Diagnosis

Conditions that can mimic GLS include:

• Other inherited liver disorders, such as Dubin-Johnson syndrome and Rotor syndrome
• Acute or chronic hepatitis
• Biliary obstruction
• Medications that can cause hyperbilirubinemia

Treatment

Treatment for GLS is usually not necessary, as the condition is benign and does not typically cause any significant health problems. However, managing bilirubin levels may help reduce symptoms.

Treatment options include:

• Lifestyle modifications, such as avoiding fasting and dehydration
• Medications, such as phenobarbital or ursodeoxycholic acid, which can increase UGT1A1 activity
• Phototherapy, which uses ultraviolet light to break down bilirubin

Prognosis

The prognosis for GLS is generally excellent. Most individuals with GLS live normal, healthy lives. However, rare complications can occur, such as:

• Gallstones
• Liver cirrhosis
• Liver failure

Management

Management of GLS focuses on monitoring for complications and providing supportive care during periods of increased bilirubin levels. Regular follow-up with a healthcare provider is recommended for individuals with GLS.

Genetic Counseling

Genetic counseling is recommended for individuals with GLS who are considering having children. The condition is inherited in an autosomal dominant manner, meaning that only one copy of the mutated gene is needed to cause the disorder.

Conclusion

Gilbert-Lereboullet syndrome is a common, inherited condition that affects the liver. It is usually benign and does not require treatment. With appropriate management, individuals with GLS can live normal, healthy lives.