Alagille Syndrome

00:01 Okay, so let’s start to look at some of these problems one at a time and try and identify what could be the cause of a child’s conjugated hyperbilirubinemia.

00:14 Here’s an example. A neonate is born and has persistent direct hyperbilirubinemia and you notice syndromic abnormal facies.

00:25 What should you suspect? The answer is Alagille Syndrome.

00:30 Let’s look at Alagilles a little bit more carefully.

00:33 The signs and symptoms of Alagilles are generally related to a number of different organs that can be involved.

00:42 First, we will see cholestasis in these children.

00:45 They will have a conjugated hyperbilirubinemia and that cholestatis may result in liver problems as well.

00:53 Frequently these children’s have congenital heart disease, something like Tetralogy of Fallot, so a murmur is often appreciated.

01:02 And lastly these children can develop posterior embryotoxon in the eye which may cause problems down the road and it’s something that you have to watch out for.

01:13 So here are some examples of some patients with syndromic facies consistent with Alagille’s.

01:20 You can notice triangular facies, a large prominent forehead, a wide nasal bridge, a small pointed chin and deep set eyes.

01:29 These are all findings consistent with the Alagille Syndrome.

01:33 This diseases is autosomal dominant. It’s a defect in the short arm of chromosome 20 on 20p12 and they usually have de novo mutations, that is to say, the parent doesn’t have alagille’s this is a new mutation, but absolutely you wanna get a family history as well.

01:55 What you’ll find on these patients if you were to biopsy them is a paucity of interlobar bile ducts including hepatic development leading to cholestasis and you can see that around the bile ducts we have some inflammation here and some problems.

02:11 So let’s look at how we would make a definitive diagnosis.

02:17 Typically in these children we need to see three out of five physical features.

02:22 We need to see evidence of cholestasis and then we’ll usually end up doing a liver biopsy on these children.

02:30 For patients with mild disease, we’ll treat them with ursodeoxycholic acid.

02:35 This helps facilitate bile flow through the abnormal biliary tract and allows the liver to not be so backed up.

02:44 Remember, the patients with liver failure may develop pruritus or itching and it can be very severe and generally we’ll treat that symptomatically with an antihistamine like diphenhydramine or Benadryl.

02:57 For patients with severe disease they often proceed to liver transplant.

03:02 Remember, that in patients with this problem, they are going to have a decrease of ability to absorb fat soluble vitamins.

03:13 These children require extra supplementation of the fat soluble vitamins A, D, E, and K and they also often get zinc as well.