congenital bile acid synthesis defect 3

Congenital bile acid synthesis defect 3 is a severe liver disorder that presents in the neonatal period with cholestatic liver disease, marked by jaundice, acholic stools, and failure to thrive. It is caused by pathogenic variants in the CYP7B1 gene, which disrupt a critical step in bile acid synthesis. The condition follows an autosomal recessive inheritance pattern, meaning that affected individuals inherit two copies of the altered gene, one from each parent. It is very rare, affecting fewer than 1 in a million people.

The clinical presentation is dominated by severe liver-related findings. Affected newborns typically exhibit neonatal cholestasis with persistent jaundice, acholic stools, and failure to thrive. Additional consistent features include hepatomegaly, splenomegaly, and laboratory abnormalities such as elevated alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase levels, as well as prolonged prothrombin time and hyperbilirubinemia. Histologic features seen on liver evaluation include cirrhosis, hepatic bridging fibrosis, bile duct proliferation, and ductal bile plugs, with hematochezia also reported. Not all individuals experience every feature, and severity varies considerably.

This condition is caused by pathogenic variants in the CYP7B1 gene, which encodes an enzyme essential for the synthesis of bile acids. Disruption of this enzyme impairs normal bile acid production, leading to toxic accumulation of intermediates and resulting in severe liver injury. It is inherited in an autosomal recessive pattern, which means that both parents must carry one copy of the variant for an affected child to result. This condition is more common when parents share a common ancestor, as the chance that both carry the same rare genetic variant is increased. Genetic counseling is recommended for families to understand recurrence risks and discuss testing options.

Currently, management focuses on supportive care and symptom management, with treatment tailored to the individual. There are no foundational or targeted therapies specifically approved for this condition, so care is provided by a multidisciplinary team experienced in managing complex liver disorders. Regular surveillance is an essential part of long-term care, with monitoring to detect complications such as progressive liver dysfunction and hepatic failure at an early stage. Patients and families are encouraged to discuss treatment options with their healthcare team and consider genetic counseling to address inheritance concerns and family planning.

The outlook for individuals with congenital bile acid synthesis defect 3 is variable and depends on the severity of liver involvement and the timeliness of supportive management. With current standards of care, many individuals benefit from ongoing surveillance and interventions that help manage complications, although the disease course remains challenging. Outcomes described in medical literature continue to evolve as standards of care improve, and families often find it helpful to connect with specialists experienced in managing such complex liver conditions. Genetic counseling is also recommended for guidance on family planning and understanding potential recurrence risks.

Clinical trials are underway exploring new treatment approaches for congenital bile acid synthesis defect 3. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.