Wilson's Disease (Hepatolenticular Degeneration)

00:01 Here, we have Wilson’s disease.

00:03 And Wilson’s disease, it is an autosomal recessive disease in which there is going to be a defect in copper transportation.

00:12 So think about copper, please.

00:14 And how it’s extremely, extremely, important for us to have it so that we have proper metabolism or should I say, proper creation and synthesis of collagen.

00:25 And so you all have heard of what’s known as oxidase, lysyl oxidase.

00:31 So, in biochemistry, when you talked about collagen synthesis, you talked about two major enzymes, one requiring vitamin C and that was hydroxylase, lysyl and prolyl.

00:41 The other major enzyme that was responsible for some of the triple helix movement or should I say stabilization of the collagen or was because of the copper.

00:51 Results in excessive serum copper.

00:53 What do you mean by excessive serum copper? Well, it’s the fact that you might have excess free copper that’s floating around.

01:02 Well, how can you call this a copper disease and yet, you have excess free copper? Because I said specifically, it’s a copper transportation disease.

01:11 So remember the – We talked about this earlier, the transporter from the liver for copper is called ceruloplasmin.

01:18 And that’s where the problem is.

01:20 If you have a deficiency of ceruloplasmin, then you decrease the bound, but the free is allowed to run free.

01:28 And where all does the free copper then accumulate? It can accumulate in the basal ganglia, and when it does, it may result in, well, Parkinson-like type of movement disorder.

01:39 The free copper could accumulate in the iris.

01:41 We then call this Kayser-Fleischer.

01:43 And the free copper of course could accumulate in the heart and in the liver causing respective diseases.

01:49 The copper deposition into liver, kidney, cornea, in CNS, and particularly in the basal ganglia, our topic here, ladies and gentlemen, being what? Movement disorder.

02:01 So with Wilson’s, what are your clinical features? Well, if you’re affecting the basal ganglia, obviously, you’re going to expect Parkinson type of movement disorder, tremors, hyperkinetic movement, parkinsonism, dysarthria, cognitive, personality and mood disturbance because this free copper, man, it is damaging the brain anywhere and everywhere.

02:23 If you take a look at the iris in this individual with Wilson’s disease, you’ll notice the areas in the iris in which they then appear as being destroyed or lesioned.

02:33 This is then referring to what’s known as Kayser-Fleischer ring.

02:38 A golden brown or greenish discoloration of the limbus of the cornea and due to copper deposition, obviously free copper.

02:47 If you were to then check for serum or labs, you would expect there to be increased or elevated free serum copper, and what did I say, where did you want to begin with this disease? It’s the fact that it’s a transportation disease.

03:00 Thus, decreased ceruloplasmin.

03:06 Elevated 24-hour urine copper as you can imagine, and that being the most important test for screening and diagnosis of course would be by biopsy to confirm your disease or diagnosis of Wilson’s disease.

03:20 Management: Chelation.

03:22 Penicillamine.

03:24 And we have something called trientine with zinc.

03:28 Now, with penicillamine, interesting issue.

03:31 With penicillamine, it may then actually cause damage to the kidney.

03:36 There’s every possibility that over a long period of time with penicillamine, it may result in something called your membranous glomerulonephropathy and we talked about that earlier.

03:47 Keep that in mind, please.

03:48 Kidney disease with penicillamine.

03:53 Important note: Always think about Wilson’s disease in a young patient with a movement disorder or atypical type of psychiatric presentation.

04:00 That’s something that you want to keep in mind.