Alagille Syndrome Diagnosis

Diagnosis and Management of Alagille Syndrome The first documentation of Alagille Syndrome was by a pediatric doctor named Daniel Alagille, in France of 1969. Later in 1973, Doctor Watson and Doctor Miller noted that the same disease also runs dominantly within a family, suggesting that it might be an inherited condition. By 1975 the specific symptoms and conditions were laid out and thus named Alagille Syndrome, also referred to as Alagille-Watson or Watson-Miller syndrome. The primary characteristic of Alagille Syndrome is the scarcity of interlobular bile ducts within the liver. Patients will also have at least three of the following five clinical features, chronic cholestasis, cardiac anomalies, butterfly vertebrae, posterior embryotoxon
With the onset of the JAG1 mutation starting from the formation of the zygote, the fetus would start having problems with the cell development signal pathways. The primary organ affected by this would be the liver, reducing the amount of interlobular bile ducts. Bile ducts are important to carry bile that is being produced by the liver to the gall bladder for storage, and into the intestines for fat digestion. There are no problems with the liver producing a sufficient amount of bile, rather it just slowly trickle down as if there’s a traffic jam on the freeway due to lane closure. Ultimately this causes a condition called chronic cholestasis, which is found in 91% of the patients with Alagille Syndrome. Patients with chronic cholestasis would have fatty stool, jaundice, or malabsorption of nutrients, due to the insufficient amount of bile actually reaching the intestines for fat digestion. A young patient with chronic cholestasis might cause the physician to consider a more common hepatic disease called Biliary Atresia. The distinctive features of Biliary Atresia are the abnormal growth of the extra-hepatic bile ducts (common bile duct and common hepatic duct), in contrast to Alagille Syndrome’s abnormal intra-hepatic bile ducts. [9]. Alagille Syndrome can be effectively distinguished from Biliary Atresia in a child with suspected liver
The JAG1 gene is responsible for the execution of the NOTCH signaling pathway, meaning the cells activate JAG1 in order to activate NOTCH2. NOTCH2 mutations can occur as well, as seen in 10% of the patients, however JAG1 seems to be more prone to mutation. Two thirds of the patients inherited this from their parents, while one third of the patients are the first generation to have this mutation.
It is an autosomal dominant disorder, meaning only one parent needs to have this gene for the symptoms to manifest itself. Humans have 23 pairs of chromosomes, one from each parent, meaning there is a 50% chance of this disease being passed if one parent is affected. If a child is presented with chronic cholestasis, it is highly suggestive of Alagille Syndrome if someone within the family have it as well. There are other telltale signs of Alagille Syndrome which could be used to differentiate it from other congenital diseases such as Biliary Atresia. While the main concern is the bile ducts within the liver, the defect in the cell signal pathway caused by JAG1 gene also affects the development and growth of the cardiac and skeletal system. The most common cardiac defects is pulmonic stenosis found in 91% of the