Unraveling Alagille Syndrome

Rare diseases are defined as those that occur with a prevalence of less than 5 cases per 10,000 people. Most cases appear in the pediatric age, given the high frequency of diseases of genetic origin and congenital anomalies. The pharmaceutical industry is not interested in this type of disease since research is very expensive and the target population that its products can reach is low, so the business is not profitable. For this reason, researchers tend to make up for this deficit through collaborations and attracting public money to advance in improving the life expectancy and quality of life of those who suffer from them.

One of these diseases is Alagille Syndrome, a hereditary disease characterized by alteration of the bile ducts associated with other malformations such as cardiological, ophthalmological, renal and vertebral alterations.

In 1993, a group was created in the United States for the study of this disease, Global Alagille Alliance, whose mission is to mobilize resources, facilitate international connections for the study of the disease and promote treatments that improve the lives of people affected by Alagille Syndrome. of Alagille. In recent years, 67 centers distributed in 29 countries in North America, Europe and Asia have joined with the aim of better understanding the natural history of this disease and being able to establish priorities in its diagnosis and treatment.

Likewise, the Biodonostia Health Research Institute (including Dr. Luis Bujanda, head of the Institute’s Hepatic and Gastrointestinal Diseases Area, and researcher at the University of the Basque Country (UPV/EHU), and Dr. Jesús M. Bañales, head of the Institute’s Liver Disease Group), the Cruces Hospital in Baracaldo, the Vall d’Hebron University Hospital and the San Joan de Deu Hospital in Espluges de Llobregat have tried to join forces with this project.

Dr. Luis Bujanda. (Photo: UPV/EHU)

After years of work, it has been possible to collect all the information possible from 1,433 children with this syndrome. It has been identified that itching (pruritus) is the first manifestation that is produced by accumulation of bilirubin. Also that 60% of children with high bilirubin in the early years end up requiring a liver transplant. The evolution after liver transplantation is very good, with 88% of children alive after 20 years of transplantation. 10% of children who did not receive a transplant end up dying after a few years.

Children without increased bilirubin in the early years have a better prognosis throughout later years. The development of drugs that improve cholestasis (decrease or absence of the normal flow of bile from the liver to the duodenum) in the first years of life is essential to change the prognosis of these patients. The determination of bilirubin levels in the first months of the newborn is decisive to detect this disease.

The most recent study in this line of research, and which includes the latest findings, is entitled “Natural History of Liver Disease in a Large International Cohort of Children with Alagille syndrome: Results from The GALA Study”. And it has been published in the academic journal Hepatology. (Source: UPV/EHU)