From the Guidelines
The disorder that makes people turn yellow due to genetic reasons is Gilbert's syndrome, a common and benign condition that affects about 3-7% of the population, particularly males, and is caused by a mutation in the UGT1A1 gene, which reduces the activity of an enzyme needed to process bilirubin. This condition is characterized by slightly elevated levels of unconjugated bilirubin in the blood, leading to yellowing of the skin and eyes (jaundice) during times of stress, illness, fasting, or physical exertion 1. According to the guidelines on the management of abnormal liver blood tests, Gilbert's syndrome is the most common cause of an isolated elevated bilirubin concentration, and it is usually due to impaired conjugation via reduced activity of the enzyme glucuronyltransferase 1.
Key Characteristics of Gilbert's Syndrome
- Caused by a mutation in the UGT1A1 gene
- Reduces the activity of an enzyme needed to process bilirubin
- Leads to slightly elevated levels of unconjugated bilirubin in the blood
- Causes yellowing of the skin and eyes (jaundice) during times of stress, illness, fasting, or physical exertion
- Affects about 3-7% of the population, particularly males
Importance of Accurate Diagnosis
It is essential to accurately diagnose Gilbert's syndrome to avoid unnecessary testing and anxiety when mild jaundice appears during illness 1. In contrast, Crigler-Najjar syndrome type I, another genetic disorder that affects bilirubin processing, is a more severe condition that requires prompt treatment to prevent kernicterus 1. However, Gilbert's syndrome is a benign condition that does not lead to liver damage or other health problems, and no treatment is typically needed 1.
Interaction with Other Medications
It is also important to note that individuals with Gilbert's syndrome may require adjusted doses of certain medications, such as irinotecan, which is used to treat colon cancer 1. The UGT1A1 gene is involved in converting substrates such as bilirubin into more soluble forms, and deficiencies in UGT1A1 can result in conditions associated with accumulation of unconjugated hyperbilirubinemias, such as Gilbert's syndrome 1. Therefore, irinotecan should be used with caution and at a decreased dose in patients with Gilbert syndrome or elevated serum bilirubin 1.
From the Research
Disorder Description
- The disorder that makes people turn yellow sometimes for a genetic reason is known as Crigler-Najjar syndrome or Gilbert's syndrome, both of which are caused by mutations in the UGT1A1 gene 2, 3, 4.
- Crigler-Najjar syndrome is characterized by severe indirect hyperbilirubinemia from birth with normal liver function, while Gilbert's syndrome is a mild form of unconjugated hyperbilirubinemia 3, 4.
Causes and Symptoms
- Crigler-Najjar syndrome is caused by a total or partial deficiency of the UDP-glucuronosyltransferase enzyme, leading to the accumulation of bilirubin in the body and resulting in yellow skin and eyes (jaundice) 2, 3.
- The symptoms of Crigler-Najjar syndrome can be apparent in the neonatal period, and patients are at risk of developing kernicterus, a complication that can cause brain damage 3, 5.
- Gilbert's syndrome is also caused by a reduction in the activity of the UDP-glucuronosyltransferase enzyme, but to a lesser extent than Crigler-Najjar syndrome, resulting in mild intermittent jaundice 4.
Treatment and Management
- Patients with Crigler-Najjar syndrome type II can respond to phenobarbital therapy, which can decrease their chances of getting bilirubinemia by 60-70% in 3 weeks 2.
- Phototherapy can also be used to manage Crigler-Najjar syndrome, especially in neonates, but the only definitive treatment is liver transplantation 3, 5.
- Patients with Gilbert's syndrome may not require treatment, but phenobarbital and phototherapy can be used to manage symptoms in some cases 6, 4.