First reported case links Alagille syndrome with biliary atresia
Infant’s liver disease improved after surgery when medication failed
Written by |
A baby girl with Alagille syndrome and related liver problems that were not responding to standard medication was also diagnosed with a rare liver disease called biliary atresia, representing the first report of both conditions occurring together.
“This unique scenario highlights the importance of comprehensive evaluation in complex cholestasis and expands our differential diagnostic reasoning,” the researchers wrote in the study, “Coexistence of Alagille syndrome and biliary atresia in a neonate: a case report,” published in BMC Pediatrics.
Understanding cholestasis and overlapping liver conditions
Cholestasis refers to slowed or stalled flow of bile, a digestive fluid, from the liver to the intestines, which can cause liver damage. It is a feature of both Alagille and biliary atresia.
After biliary atresia was diagnosed, the girl’s liver problems improved after treatment with the Kasai surgery, typically the first-line treatment of biliary atresia that creates a new route for bile to flow into the intestines.
Despite the favorable outcomes over eight months of follow-up, “the generalizability of the treatment approach and its outcomes need validation through larger, multi-center studies and longer follow-up periods,” the researchers wrote.
Alagille is caused by genetic mutations that can lead to a wide range of abnormalities, including problems in the liver and the heart, as well as characteristic changes in the shape of the face.
Liver issues in Alagille are typically due to fewer bile ducts, the tubes that transport bile from the liver to the intestines. This leads to cholestasis, which can cause bile to build up in the liver and damage the organ, leading to symptoms such as jaundice (yellowing of the skin and white parts of the eyes) and pale stools.
These symptoms can overlap with those of biliary atresia, another rare disease in which blocked or damaged bile ducts, present from birth, slow bile flow.
“Although both disorders present with cholestasis in infancy, their underlying [cause], anatomical defects, and management strategies are fundamentally distinct,” the researchers wrote.
Biliary atresia requires surgery but may be misdiagnosed
Biliary atresia is mainly treated with the Kasai surgery, also known as Kasai portoenterostomy, to restore bile flow. However, a previous study suggested that performing it in children “misdiagnosed with BA [biliary atresia] but later confirmed to have isolated ALGS [Alagille syndrome] may accelerate [liver] deterioration,” the researchers wrote.
Now, a team of researchers described the case of a 1-month-old girl of Han Chinese origin who was diagnosed with both Alagille and biliary atresia. This is “the first confirmed case of ALGS and BA coexistence,” the researchers wrote.
The baby girl was admitted to the hospital with persistent jaundice, pale stools, and abdominal swelling. Physical examination showed liver enlargement and characteristic facial features of Alagille: a broad forehead, deep-set and widely spaced eyes, a straight nasal bridge, and a pointed chin forming a triangular face. Blood tests showed high bilirubin levels and elevated liver enzymes, consistent with cholestasis and liver dysfunction.
Genetic testing detected an Alagille-causing mutation in the JAG1 gene, confirming the diagnosis of Alagille syndrome. Family testing showed the same mutation in the father. Ultrasound imaging showed an enlarged liver, whereas the gallbladder (the organ where bile is stored) and the common bile duct could not be seen, raising suspicion for biliary atresia.
The baby was treated medically for three weeks with glutathione and diammonium glycyrrhizate to protect the liver, and ursodeoxycholic acid (UDCA) — marketed as Actigall and Urso in the U.S. and available as generics — to improve bile flow. However, her jaundice and pale stools did not significantly improve.
Surgery pursued after limited response to medical treatment
Because her symptoms did not improve with medication, doctors performed laparoscopic exploration, a minimally invasive, camera-guided procedure used to examine the abdominal organs.
They observed an enlarged, dark, stiff liver with spider-like surface blood vessels typical of liver disease. The gallbladder was very small and solid, preventing the injection of a contrast dye to visualize the connecting bile ducts. These findings confirmed biliary atresia in a child already diagnosed with Alagille syndrome.
Doctors then performed Kasai surgery to restore bile flow. After the procedure, the girl continued on glutathione, diammonium glycyrrhizate, and UDCA, and was also given antibiotics, corticosteroids (anti-inflammatory medications), fluids, and nutritional support.
Her jaundice eased markedly, and her stools turned normal yellow, indicating better bile flow. At more than eight months of follow-up, she remained free of jaundice, with normal stool color, and biochemical and ultrasound examinations showed no significant abnormalities.
“For infants with a confirmed diagnosis of BA—even in the context of [co-existing] ALGS—our experience suggests that proceeding with early Kasai surgery remains a viable and potentially beneficial approach to modify disease progression, contrary to concerns raised in cases of misdiagnosed ALGS alone,” the researchers wrote. This case “further provides a clinical foundation for future research into potential common [disease-associated] pathways between these two distinct disorders.”
