What Is Maple Syrup Urine Disease?
The name “maple syrup urine disease” may sound benign, but it is a serious medical disorder that needs diagnosis and treatment to reduce the chance of lifelong complications or even death. This metabolic condition is a recessive genetic disorder that affects the body’s amino acids that are structured in branched chains.
Since the disorder is characterized by a distinct smell, it is often diagnosed in early infancy as long as the disease is presenting in a classic way. Prompt diagnosis and treatment can mitigate some of the more severe possible outcomes of the disorder.
1. Where Did the Name Maple Syrup Urine Disease Come From?
Maple syrup urine disease gets its name due to the smell of the urine associated with individuals who have the disorder. Sufferers from the condition can go into a type of metabolic emergency during which the urine begins to smell strong and sweet, similar to the smell of maple syrup.
Not all areas of the world are familiar with the smell of maple syrup. An herb called fenugreek, often used by breastfeeding mothers to increase milk production, has a similar smell. In areas unfamiliar with maple syrup, the smell of fenugreek in the urine can be used as a diagnostic tool for MSUD.
2. What Causes Maple Syrup Urine Disease?
MSUD is a genetic disorder that is caused by a mutation in one or more of the four specific protein-producing genes that are responsible for breaking down certain amino acids. More specifically, individuals with MSUD are unable to properly break down the amino acids leucine, valine and isoleucine. These amino acids are found in many common foods that are high in protein, most notably dairy products. When the body is unable to properly break down these amino acids, they begin to accumulate. As the build-up progresses, the levels can become dangerous and in the worst cases, toxic. This is why it is so important to obtain a diagnosis and come up with a treatment plan, especially for infant patients.
In most cases, neither parent has maple syrup urine disease. Since the condition is recessive, both parents must either have or be carriers of the genetic mutation to pass it on to a child. Even when both parents are carriers, the children are more likely to also be carriers than to develop MSUD. For this reason, MSUD is considered a rare condition. A child of two carrier parents is actually just as likely to not be a carrier at all as he or she is to develop the condition.
3. How Is MSUD Diagnosed?
Maple syrup urine disease can be detected in newborns through the routine newborn screening process. Since symptoms in newborns can become evident within the first few days of life, a positive screen means treatment can begin before symptoms worsen. Some symptoms can occur immediately that indicate a possible MSUD diagnosis. Infants who are lethargic, irritable and eating poorly may have the condition, though these symptoms can also be signs of other conditions.
There are several types of MSUD, so a diagnosis for either a child or adult will fall under one of four general categories. The category determines what types of treatment are available and gives the physician an overall idea of the severity of the disorder. Patients are categorized into classic, intermediate, intermittent or thiamine-response MSUD. If the diagnosis cannot be placed into one of these categories, the patient will be diagnosed with unknown origin or unclassified MSUD.
4. What Is Classic MSUD?
Classic maple syrup urine disease originates in newborn infants and presents with symptoms nearly immediately, typically within the first three days of life. The earliest symptoms are increased irritability, inability to eat properly and general lethargy. Symptoms become more evident over a short period of time and can develop into neurological concerns. Convulsive movements and atypical movements are common.
Classic MSUD is considered the most severe form of the disorder. If swift treatment does not occur, the infant can become more convulsive and eventually comatose. Advanced symptoms are neurological in nature and can lead to full respiratory failure as well as death within the first few weeks. Even with treatment, it is not uncommon for individuals with classic MSUD to have intellectual and behavioral disabilities.
5. What Is Intermediate MSUD?
Although many of the symptoms of classic MSUD occur in individuals with intermediate MSUD, the general level of enzymes is greater and the symptoms are not as immediately critical. Symptoms for intermediate MSUD can arise at any time between five months and seven years of age.
Those with intermediate MSUD can still present with intellectual and behavioral difficulties and generally respond best to a treatment plan similar to that for the classic type. Although the enzyme activity is greater than with classic MSUD, it is not enough to avoid the typical symptoms associated with the disorder. The symptoms usually just present at a less severe level.
6. What Is Intermittent MSUD?
Intermittent maple syrup urine disease is less severe than either the classic or intermediate diagnosis. Individuals diagnosed with the intermittent condition do not experience symptoms from the disorder at all times. They also do not typically have deficiencies in neurological function, growth or intellectual ability. Since individuals with intermittent MSUD do not experience symptoms all the time, the treatment plan is different from those with the other sub-types.
Those with intermittent MSUD can still develop concerning and potentially dangerous symptoms during an episode of metabolic distress, including the possibility of brain damage, coma or, in the most extreme metabolic crises, death. There are certain activities that can bring on an episode of intermittent MSUD symptoms, such as illness or infection, excessive stress or a period of fasting. It is important for individuals with this type of MSUD to self-monitor for changes.
7. What Is Thiamine-Response MSUD?
Thiamine-response MSUD is a specific subset of MSUD that affects thiamine disproportionately. Like intermediate MSUD, those with this category of the disorder can experience symptoms at any time, although they are not typically as severe as those with classic MSUD.
Those with thiamine-response MSUD can have neurological, intellectual and behavioral difficulties but are usually not diagnosed as newborns since the symptoms usually do not begin until later. Enzyme activity is higher than with the classic variation of MSUD but is not sufficient enough without treatment.
8. What Is Late-Onset MSUD?
Although late-onset maple syrup urine disease is not an official diagnostic subcategory, it applies to anyone who is diagnosed later in life. When enzyme activity is sufficient enough to not cause symptoms in infancy but become evident in times of stress or illness, it can possibly lead to a late-onset diagnosis.
A late-onset diagnosis usually falls under the category of intermittent MSUD since the symptoms only arise during times of metabolic distress. Most other types of this disorder have enzyme activity consistently low enough to cause symptoms at all times without treatment.
9. How Is MSUD Treated?
The treatment plan for maple syrup urine disease depends on the type and the severity of the illness. All patients with this condition should be monitored regularly for signs of metabolic stress. Monitoring can be done by testing the urine for ketones and taking regular blood samples to test for the levels of amino acids that may be on the rise. Any time metabolic stress is likely, such as during times of rapid growth or illness, additional testing should be completed to review the entire metabolic panel for concerns.
Along with regular monitoring, those suffering from MSUD need to adhere to a specific diet to maintain balance. The diet requires lowering the intake of protein-rich foods so that the amino acids leucine, isoleucine and valine are not able to build up in the body as easily. Protein-rich foods to avoid include meat, dairy, nuts, eggs, soy, legumes, gluten and other related foods. Since the diet is so limited, individuals with MSUD need to take vitamins and supplements to receive some of the nutrients that they may be missing.
10. What Is the Prognosis for MSUD?
Early identification, regular monitoring and dietary restrictions are all important parts of the MSUD treatment plan. When an infant is diagnosed as a newborn and treated quickly, it lowers the chance of significant developmental issues. For many individuals with this disorder, monitoring and dietary limitations make enough of an impact to not need any more intervention. However, for more severe cases, diet and regular monitoring may not be enough to prevent regular episodes of metabolic stress and more invasive measures must be taken.
Some people with MSUD are able to improve the prognosis only with advanced intervention. Those with thiamine-response MSUD can eat higher levels of protein than other types, but only if these individuals also receive thiamine doses at a high level. In other cases, the only way to eliminate symptoms is through a liver transplant. Organ transplants also come with their own risks, including the surgery itself, chance of rejection and issues with taking immunosuppressants. With more studies on this rare condition, even better treatment plans can be developed.
