Alagille syndrome


Alagille syndrome is a genetic disorder comprising a series of symptoms and clinical signs. This rare disease affects 1 child in 100,000 births. It is caused by a chromosomal modification of the JAG1 gene on chromosome 20 or of the NOTCH2 gene on chromosome 1. The mutation may either occur during the embryonic period and, in this case, it is considered as de novo, or be inherited from a parent. The diagnosis can thus be confirmed by a gene analysis.

Prolonged jaundice (icterus) in the newborn often is the first clinical sign of this disease. This icterus is associated with neonatal cholestasis (biliary stasis) due to an insufficient number of bile ducts. This reduced number of bile ducts inside the liver also results in an accumulation of conjugated bilirubin in the blood. Besides the jaundice, the child may present itching, called pruritus, caused by an elevated level of conjugated bilirubin. The other symptoms and signs of Alagille syndrome are heart defects (pulmonary stenosis being the most common one), vertebral malformations with an unusual butterfly shape of the bones of the spinal column that can be seen in an x-ray, characteristic facial features, an anomaly of the iris called embryotoxon (fat depot around the iris), kidney problems and shortness.

Treatment depends on the manifestation of symptoms that may vary. Some patients mainly only have heart problems. In case of persistent jaundice, dietary measures are recommended in order to ensure good growth and avoid vitamin deficiencies. Pruritus can be alleviated by a drug called rifampicin. Liver transplantation is indicated when the pruritus is refractory to drug treatment or when the disease develops and results in the complication of chronic liver disease.

Dr. Veronica Varela