Crigler-Najjar syndrome type 2

Crigler-Najjar syndrome type 2 is a hereditary disorder of bilirubin metabolism that results in elevated levels of unconjugated bilirubin due to reduced activity of a critical liver enzyme. This milder form of Crigler-Najjar syndrome is caused by changes in the UGT1A1 gene, which plays a key role in processing bilirubin. The condition is inherited in an autosomal recessive pattern, meaning that an affected individual has received altered copies of the gene from both parents. Although precise prevalence estimates are not available, the condition is considered uncommon.

The main clinical features of Crigler-Najjar syndrome type 2 are persistent jaundice and unconjugated hyperbilirubinemia, with both features being present in all affected individuals. Patients typically present with a noticeable yellow discoloration of the skin and eyes, which is often detected during routine examinations or when jaundice becomes apparent. Not all individuals experience additional complications, and severity varies considerably between patients.

This condition is caused by alterations in the UGT1A1 gene, which encodes an enzyme that is crucial for the conjugation of bilirubin in the liver. A reduction in the inducible activity of this enzyme leads to a buildup of unconjugated bilirubin. Crigler-Najjar syndrome type 2 is inherited in an autosomal recessive manner, meaning that both parents must carry a variant in this gene for their child to be affected. Genetic counseling is recommended, as this information can help families understand the recurrence risk and implications for family planning.

Currently, management of Crigler-Najjar syndrome type 2 focuses on supportive care and symptom management rather than a targeted cure. As no FDA-approved or foundational therapies are available for this condition, treatment is tailored to the individual and typically involves monitoring bilirubin levels and managing jaundice. Patients are encouraged to work with a multidisciplinary team and to seek genetic counseling to better understand their options. Supportive interventions and careful follow-up remain the cornerstones of care.

The outlook for individuals with Crigler-Najjar syndrome type 2 varies, with outcomes depending on the severity of hyperbilirubinemia and the effectiveness of supportive care measures. With current standards of care, many individuals manage their symptoms well and maintain a good quality of life. Outcomes described in medical literature continue to evolve as standards of care improve, and the course of the condition can be variable. Families often find it helpful to connect with genetic counselors and specialist care teams to receive up-to-date information and guidance.

Clinical trials are underway exploring new treatment approaches for Crigler-Najjar syndrome type 2. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.