Maple Syrup Urine Disease is a metabolic syndrome which causes urine to smell like maple syrup. Learn more about this genetic disease from doctors at Meri Sehat.

Maple Syrup Urine Disease

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Iqra Mazhar

Overview

Maple syrup urine disease (MSUD) is a rare inherited condition characterized by the body&rsquo;s inability to process certain amino acids. This leads to a build-up of harmful substances in the blood and eventually in urine<a href="#accordion">[1]</a>.&nbsp; 
&nbsp;

MSUD is a rare genetic disorder that involves a deficiency of an enzyme complex, which metabolizes the 3 branched-chain amino acids (BCAAs) &ndash; leucine, isoleucine, and valine<a href="#accordion">[3]</a>. High concentrations of these amino acids in the body are very harmful, especially in children. They must be broken down and removed from the body, otherwise, it may cause several disabilities including stunted mental growth. Severe cases of MSUD may even result in death.&nbsp;

The name maple syrup urine disease comes from the sweet odor of the urine<a href="#accordion">[2]</a>. 1 in 185,000 infants worldwide suffers from this disease. Incidentally, the disease is highly prevalent in the Mennonite population, affecting 1 in 380 infants<a href="#accordion">[3]</a>.&nbsp; 
&nbsp;

There are 4 main types of MSUD. These include:

&nbsp;

<ul>
	<li>
	<h5>Classic MSUD</h5>
	</li>
</ul>

This is the most severe and the most common form of MSUD. There is little to no enzyme activity and the affected infants exhibit symptoms within 2-3 days of birth. The infants are found to be very lethargic and have poor feeding ability. This state is later followed by abnormal movements. There is a rapid decline in health, including extreme hypotonia and respiratory failure, and eventually death.

&nbsp;

<ul>
	<li>
	<h5>Intermediate MSUD</h5>
	</li>
</ul>

Compared to classic MSUD, this type of MSUD is less severe. The symptoms appear in children aged 5 months to 7 years. There are greater levels of residual enzyme activity. The symptoms are very similar to classic MSUD, but fatal neurological complications are rare. In some cases, children may even stay asymptomatic for a very long time.

&nbsp;

<ul>
	<li>
	<h5>Intermittent MSUD</h5>
	</li>
</ul>

This type of MSUD is characterized by the regular growth of the child. The onset of symptoms only occurs if something triggers the disease. The body is able to process moderate amounts of proteins in the diet.

&nbsp;

<ul>
	<li>
	<h5>Thiamine-Responsive MSUD</h5>
	</li>
</ul>

​​​​​​​Similar to&nbsp;intermittent MSUD, thiamine-responsive MSUD occurs in the later stages of the newborn&rsquo;s life. The name comes from the body&rsquo;s positive response to treatment involving high doses of thiamine (vitamin B1). Children with thiamine-responsive MSUD tend to develop a higher tolerance for the three main amino acids<a href="#accordion">[4]</a><a href="#accordion">[5]</a>.

<div>&nbsp;</div>

Signs And Symptoms

The symptoms of intermediate, intermittent, and thiamine-responsive MSUD may present themselves at any age. Usually, the onset of symptoms varies depending on the type of MSUD. The symptoms, however, are very similar to each other and mainly include:

<ul>
	<li>Sweet-smelling urine and sweat</li>
	<li>Weight loss</li>
	<li>Poor feeding ability&nbsp;</li>
	<li>Loss of appetite</li>
	<li>Vomiting</li>
	<li>Irritability</li>
	<li>Respiratory issues</li>
	<li>Tiredness and weakness</li>
	<li>Poor muscle tone</li>
	<li>Abnormal muscle movements and spasms</li>
	<li>Seizures</li>
	<li>Slurred speech</li>
	<li>Stomach pain</li>
	<li>Trouble remaining alert</li>
</ul>

<div>&nbsp;</div>

Causes

MSUD is an inherited condition &ndash; it is caused due to a defect in the gene that is passed down through families. The disease affects the enzymes needed to break down leucine, isoleucine, and valine. These amino acids tend to build up in the body and produce toxic effects that damage the brain and other organs of the body.&nbsp;

An individual can only get MSUD if they inherit 2 mutated MSUD genes, one from each parent. Carriers of the gene do not have any symptoms, but they can pass down the gene to their children<a href="#accordion">[5]</a>. 
&nbsp;

Diagnosis

In most cases, newborns go through rigorous screening and testing right after being born. Blood tests are done on the newborn baby. However, unless the baby is suffering from a case of classic MSUD, the chances of the disease presenting itself on the tests are very low; other types of MSUD are diagnosed later in the toddler years.&nbsp;

Whenever MSUD is suspected then, based on the symptoms, a blood test is ordered to check the amino acid levels in the blood, and a urine test is also ordered to check for the levels of targeted amino acids<a href="#accordion">[5]</a>.&nbsp; 
&nbsp;

Treatment

There is no cure for MSUD. The treatment mainly involves monitoring and life-long dietary management of the disease. This requires constant consultation with a pediatric nutritionist (nutrition counseling) to ensure that branched-chain amino acid dietary restriction is in practice.&nbsp;

The therapy for MSUD involves decreasing the toxic metabolites by achieving optimum BCAA (branched-chain amino acid) plasma concentration according to the set treatment ranges. The therapy also ensures that the diet promotes anabolism and, at the same time, reduces catabolism. If the patient gives a positive response to thiamine, then thiamine supplements are included in their diet.

Glucose infusions are preferred for the treatment of metabolic decompensation whereas insulin infusions are used to promote anabolism. One of the side effects to these infusions is that the blood sugar levels may change and will have to be monitored closely.

In some cases, the child may require hemodialysis or peritoneal dialysis to get rid of BCAAs and keto acids. It is likely the individual experiences low blood pressure or muscle cramps following this treatment.

Orthotopic liver transplantation is an option for children with classic MSUD. Patients with classic MSUD tend to suffer more from aggressive episodes of metabolic decompensation. While a liver transplant cannot reverse the neurological damage that&rsquo;s already occurred, it can aid in preserving the remaining function of the nervous system and also in avoiding any future episodes<a href="#accordion">[6]</a>. However, liver transplant also includes complications, like infection and organ rejection<a href="#accordion">[4]</a>.&nbsp; 
&nbsp;

MSUD can pose multiple complications, especially in severe or untreated cases. Even during treatment and management of the disease, it is common to experience extreme sickness which, in this case, is known as metabolic crises.

Metabolic crises refer to a sudden increment in the branched-chain amino acids in the body. In case the crisis is not treated, it will not only lead to neurological and physical damage, but will also prove to be fatal.&nbsp;

&nbsp;

A metabolic crisis is characterized by:

<ul>
	<li>Fatigue</li>
	<li>Vomiting</li>
	<li>Irritability</li>
	<li>Inability to stay alert 
	&nbsp;</li>
</ul>

Other complications include:

<ul>
	<li>Seizures</li>
	<li>Inflammation in the brain</li>
	<li>Inadequate blood flow to the brain</li>
	<li>Blindness</li>
	<li>Muscle tightness and spasms</li>
	<li>Intellectual disability</li>
	<li>Increased risk of <a href="https://www.merisehat.pk/disease/anxiety" target="_blank">anxiety</a>, <a href="https://www.merisehat.pk/disease/depression" target="_blank">depression</a>, and <a href="https://www.merisehat.pk/disease/attention-deficit-hyperactivity-disorder-adhd" target="_blank">ADHD</a></li>
	<li>Swelling of pancreas</li>
	<li>Coma and death</li>
</ul>

&nbsp;

When it comes to inherited diseases such as MSUD, there are no risk factors involved except for both parents being carriers of the mutated gene. Even then, the chances of the baby getting MSUD is only 25% and another 25% chances that the baby does not have the mutated gene at all. In 50% of the cases, the baby will just be a carrier of the gene.&nbsp; 
&nbsp;

Inherited diseases cannot be prevented but before having a baby, a couple can always visit a genetic counselor to help determine the risk of their child getting the condition. Proper genetic testing can tell the parents if they are carriers for a genetic disorder. 
&nbsp;

Key Points

<ul>
	<li>Maple syrup urine disease (MSUD) is a rare inherited disease where the urine of newborns smells sweet and may match the appearance of maple syrup.</li>
	<li>The disease occurs due to mutated genes that involve the inability of certain enzymes to break down leucine, isoleucine, and valine.</li>
	<li>The symptoms of MSUD include stunted mental growth, seizures, metabolic crisis, vomiting, weight loss, etc.</li>
	<li>There are 4 main types of MSUD: classic MSUD, which is the most severe; intermittent MSUD; intermediate MSUD; thiamine responsive MSUD.</li>
	<li>There is no cure for MSUD. The disease is maintained through a restricted diet where the patient cannot consume foods rich in branched-chain amino acids to maintain BCAA concentration in their blood plasma.</li>
	<li>There are several complications accompanying MSUD with the biggest and most common complication being metabolic crisis. Every patient suffers from it at some point and may even be fatal if not treated immediately.</li>
</ul>

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[1] Maple Syrup Urine Disease. NHS choices.

[2] Maple syrup urine disease: Medlineplus Genetics. MedlinePlus.

[3] Maple syrup urine disease. NORD (National Organization for Rare Disorders).

[4] Maple syrup urine disease (MSUD). Cleveland Clinic.

[5] Maple syrup urine disease (for parents) - nemours kidshealth. KidsHealth.

[6] Germaine L Defendi MD. Maple syrup urine disease (MSUD) treatment &amp; management: Medical care, surgical care, Diet. Maple Syrup Urine Disease (MSUD) Treatment &amp; Management: Medical Care, Surgical Care, Diet.