Maple Syrup Urine Disease (MSUD) (Nursing)

00:01 In this presentation, we're going to talk about Maple Syrup Urine Disease.

00:05 Which might sound a little bit fun, but it really isn't for the patients.

00:10 So what does Maple Syrup Urine Disease mean? It creates a branched-chain ketoaciduria.

00:18 Now what this means is that it's this branched chain amino acids, those BCAAs that we hear about those are really affected by this disease process.

00:29 So in a normal metabolic pathway, we take in leucine, isoleucine, and valine and then we have some enzyme activity.

00:38 So there's a couple of steps. You see here, the BCAT.

00:42 That really is the first enzyme activity that happens.

00:46 And then after that, we have another enzyme that helps to break down these amino acids.

00:51 And the end result is that there's multiple products that are needed for energy and for metabolism in your body.

00:59 Now, what happens with Maple Syrup Urine Disease is that the patient is missing the enzyme in that second step.

01:07 So they're not able to break down these amino acids.

01:10 And the end result is a buildup of keto acids, and this becomes very toxic in the body.

01:19 There are several phenotypes of Maple Syrup Urine Disease.

01:23 So we have a classic, intermittent, intermediate.

01:27 One that's thymine responsive. One that's E-3 deficient.

01:32 So what does that mean for our patients? Generally, in early infancy, we're going to see Classic Maple Syrup Urine Disease and possibly the E3-deficient.

01:43 Now, we don't talk a lot about the E3-deficient type of Maple Syrup Urine Disease, because it is very rare.

01:50 And there's not that many times where we're going to have to manage these patients.

01:56 Now, throughout childhood, we might see more of the intermittent, the intermediate, and the thiamine responsive types.

02:06 So, what are some signs and symptoms that we might see in patients that are experiencing this? You might see psychomotor delay.

02:14 And what this means is that everything for the patient kind of slows down.

02:19 So if you have an infant that is moving slowly or reacting slowly, then that is an indication of psychomotor delay.

02:27 They might also be having feeding problems and this might directly relate to the psychomotor delay, meaning that they can't coordinate the second swallow that they need to feed.

02:38 And then the hallmark of this disease is that their urine is going to have this maple syrup odor to it.

02:45 It's really hard to miss.

02:50 What happens with Classic Maple Syrup Urine Disease? So these patients will usually develop a ketonuria within 48 hours after birth.

02:59 So Classic Maple Syrup Urine Disease is going to present in the newborn in the form of irritability, possibly encephalopathy.

03:08 They're going to have poor feedings, so they might not be able to latch onto their bottle.

03:12 You might notice vomiting, and lethargy.

03:15 And you may see dystonia.

03:17 So what does dystonia mean? Just really means that those muscles aren't working the way we would expect them to.

03:22 So the infant might look a little bit floppy, or they might actually look like their muscles are a little too stiff.

03:30 Additionally, if you move into that first week, you're going to have pretty similar symptoms.

03:36 But you might have the addition of the infant developing apnea.

03:41 So this means that they're going to have periods of time where they stop breathing altogether, or they might develop seizures and signs have cerebral edema.

03:49 Meaning that that brain is actually swelling.

03:53 So the initial symptoms may not develop until the infant is four to seven days old.

03:58 It really depends on the amount of protein that's in the original feeding regimen.

04:03 And for this reason, breastfeeding infants, you might not notice these symptoms until the second week of life, where as a baby that is being fed formula that's fortified with amino acids, those babies are going to present earlier.

04:20 Now, patients with Classic Maple Syrup Urine Disease, even if they're being treated are going to be at risk for metabolic intoxication.

04:29 And what does that mean? These are episodes that can be caused by increased catabolic states.

04:36 Now, increase catabolic states can be an intercurrent illness, perhaps they have sepsis, maybe there was heavy exercise.

04:44 Think of a person that's going to be running a marathon.

04:47 Somebody that sustained a serious injury, has undergone surgery.

04:52 All of these are significant stressors on the body, and they put these patients at particular risk for metabolic intoxication.

04:59 And metabolic intoxication just means that they're going to see some of those symptoms even if we've been able to manage them up until now.

05:08 So, they might have seizures, they might have signs and symptoms of neurological impairment.

05:15 So, vomiting, epigastric pain, muscle fatigue, and anorexia are also common when you're having a metabolic emergency with Maple Syrup Urine Disease.

05:27 You may also see hyperactivity, sleep disturbances, decreased cognitive function.

05:33 They may become superfluous or lethargic.

05:36 You might see that dystonia again.

05:38 They might even develop some ataxia.

05:40 So all of these symptoms are really going to give you that information that the patient is having a metabolic crisis.

05:48 This is important to recognize because even in patients that are being managed for their inborn error, if they go into this metabolic crisis, death can occur from cerebral edema and herniation.

06:01 So the second most common type of Maple Syrup Urine Disease is an intermittent.

06:05 This affects patients that have really kind of normal growth and development.

06:10 And it really is going to present with ketoacidosis during episodes of stress.

06:16 So the patient probably initially wasn't even diagnosed with Maple Syrup Urine Disease because they didn't have those symptoms as an infant, but perhaps they were injured, or became ill, or had to have surgery.

06:29 And all of a sudden their body is under stress.

06:32 So they might then present with those symptoms that we talked about earlier for the metabolic emergency.

06:40 In a case where we don't really have another reason for a patient to have that extreme of a response to say a surgical procedure, then we have to start looking for underlying causes and inborn errors of metabolism of which Maple Syrup Urine Diseases one is something that we need to keep in to backup our mind.

07:01 So these patients are also going to show signs of neurotoxicity if they're having an episode, so ataxia lethargy, then that can even progress to seizures and coma.

07:14 If we don't catch that the patient possibly has an inborn error of metabolism, then death can occur from these metabolic incidences.

07:25 So more rare is the intermediate Maple Syrup Urine Disease.

07:30 So patients can become symptomatic at any age.

07:33 Presentation is usually later because the enzyme activity in these patients is usually a little bit more than in the other types.

07:42 They again are going to present with neurologic symptoms like irritability, dystonia.

07:49 They're going to have possibly a developmental delay of variable extent, but it won't be to the extent as say The Classic Maple Syrup Urine Disease.

07:59 And you might see seizures in some patients, especially if their body is overly stressed.

08:05 So episodes of acute metabolic decompensation in these patients with Intermediate Maple Syrup Urine Disease are actually fairly rare, so it's a little bit more difficult to catch these patients.

08:19 We also have a thiamine responsive form of the Maple Syrup Urine Disease.

08:24 When we are first diagnosing patients, they will send off some genetic studies and they'll determine at that point whether the Maple Syrup Urine Disease is going to be receptive to thiamine supplementation.

08:37 In a small cohort of patients, it turns out that thiamine actually supports the stability of the enzymes and can help the patient with their symptoms.

08:47 Now, you can't only do thiamine supplementation.

08:50 They're still going to need the dietary restrictions, but the thiamine can be helpful.

08:56 Again, even in the thiamine responsive, you may have signs and symptoms that include acute neurologic symptoms, irritability, the dystonia.

09:05 They might also have mild developmental delay.

09:08 And you may see seizures in some of these patients, especially if they're not well managed.

09:16 One of the most rare forms is the E3-deficient.

09:19 We talked about that in an earlier slide.

09:23 These patients can become symptomatic at any age and the presentation is usually a bit later.

09:28 You're also going to manage this with dietary restrictions.

09:31 So, whether it's E3-deficient or another type of Maple Syrup Urine Disease, we're really going to manage it the same way.