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Maple Syrup Urine Disease

Prevention

There are no methods for prevention for developing MSUD. However, there are genetic counselors available for consultation to determine whether you or your partner are a carrier for the disease via DNA testing. DNA testing is also available to identify the disease in a fetus before it is born.

Prognosis

Diagnosing infants born with MSUD is critical to their quality of life. If infants go undiagnosed and untreated for longer than even their first week of life, irreversible damage will be observed. For instance, a delay in treatment for longer than 14 days after birth is associated with general learning disability and even cerebral palsy in the child later on. However, if treatment is even further delayed the child will likely experience serious developmental delays and will die within the first few months of life. People suffering from MSUD will have to constantly monitor their diet for the rest of their lives. They must follow a strict diet involving foods that are free of proteins. Both hemodialysis or peritoneal dialysis are used in patients with MSUD when their levels of amino acids have reached a concerning high. Once their amino acid levels are back to normal levels, they are placed on a diet free of branched chain amino acids. The patients amino acids will need to be monitored closely on a regular basis by health care providers. These health care providers will adjust the patients diets based on their amino acid levels.

Prevalence

Maple Syrup Urine Disease (MSUD) is a rare, inherited metabolic disorder. Its prevalence in the United States population is approximately 1 newborn out of 180,000 live births. However, in populations where there is a higher frequency of consanguinity, such as the Mennonites in Pennsylvania, the frequency of MSUD is significantly higher at 1 newborn out of 176 live births. In Austria, 1 newborn out of 250,000 live births inherits MSUD.

People suffering from MSUD will have to constantly monitor their diet for the rest of their lives. They must follow a strict diet involving foods that are free of proteins. Both hemodialysis or peritoneal dialysis are used in patients with MSUD when their levels of amino acids have reached a concerning high. Once their amino acid levels are back to normal levels, they are placed on a diet free of branched chain amino acids. The patients amino acids will need to be monitored closely on a regular basis by health care providers. These health care providers will adjust the patients diets based on their amino acid levels.

Risk Factors

MSUD is an inherited disorder, therefore, all children born into families with a medical history of MSUD are at risk of being affected. According to the National Organization for Rare Disorders (NORD), MSUD occurs in both males and females at the same rate. This is due to the disorder being autosomal, meaning it is inherited by means of the non-sex chromosomes. The risk for having MSUD really depends on whether or not the parents are either affected or carriers for the disorder. It is important to know that having a risk factor does not necessarily mean an individual will get the condition.

If both parents are affected by MSUD, each of their children have a 100% chance of having the disorder. On the other hand, if at least one parent carries two normal genes for the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), the disorder can not be passed on to their children. However, if both parents are a carrier for the disorder, each of their offspring have a 25% chance of receiving two mutated genes and having MSUD, a 50% chance of receiving only one mutant gene and being a carrier, and a 25% chance of receiving two normal genes and not being affected at all. For this reason, if both parents are carriers, it is possible for at least one of their children to have MSUD and the others to not. Just as it is also possible that all children may fall into that 25% chance of receiving two normal genes, resulting in no children having MSUD at all.

Diagnosis

Physicians should be cautious when diagnosing patients with MSUD due to the symptoms similar with ingesting fenugreek. It is more common to see the symptom of aroma of maple syrup in the urine in patients from Mediterranean countries and Middle Eastern countries. Fenugreek seeds contain the same compound that causes the sweet aroma of urine in MSUD, which can complicate the diagnosing process.

Subtypes of MSUD

Classic

The classic subtype of MSUD is the most common and also the most severe, often manifesting in infancy within the first few days of life. Little to no enzyme (branched-chain alpha-keto acid dehydrogenase complex) is produced in individuals with this subtype, resulting in its severity and early onset. The classic subtype can be the result of mutations in BCKDHA, BCKDHB, and DBT. Infants may appear lethargic, irritable, have little interest in feeding, and have a poor sucking response. Weight loss, irregular sleep patterns, hypertonia, and hypotonia may also occur. Additionally, the characteristic maple syrup odor may be present in the urine, sweat, and earwax of affected individuals. Individuals affected with the classic subtype may also develop behavioral problems later in life including ADHD, impulsivity, depression, and anxiety.

Intermediate

The intermediate subtype of MSUD is very rare with less than 20 reported cases. Accordingly, there is high variability in the reported phenotype. Age of onset, symptoms, and molecular explanations vary significantly on a case-by-case basis. Some cases appear to be a result of mutations in BCKDHA while others appear to be the result of a mutation in DBT.

Intermittent

Symptoms don’t appear until around 1 or 2 years of age usually after a time of stress, infection or fasting. It is a milder form of the classic MSUD because patients have about 8 to 15 percent of enzyme activity. Symptoms are present in milder forms of the classic MSUD and if left untreated can lead to coma, seizures, and brain damage.

Thiamine-Responsive

Thiamine-Responsive MSUD is relatively rare. Patients do not show symptoms until after infancy, but symptoms resemble those of intermediate MSUD. The defect in the Thiamine-Responsive MSUD is a reduced affinity of BCKD for thiamine. Individuals have about 30 to 40 percent of enzyme activity. Treatment of large doses of thiamine increase the enzyme activity, along with diet restrictions symptoms can be reduced.

E-3 Deficient MSUD with Lactic Acidosis

Some scientists believe that this subtype of MSUD should be considered its own disorder because along with the similar symptoms there are additional biochemical defects. Another name for this disease is Dihydrolipoamide Dehydrogenase Deficiency.

Genetic Screening

Maple Syrup Urine Disease is an amino acid disorder. It is diagnosed by the presence of elevated Branched-Chain Amino Acids (BCAAs) and allo-isoleucine in the blood plasma, and by Branched-Chain Hydroxyacids and Ketoacids in the urine. Newborn screening for MSUD uses tandem mass spectrometry to measure the whole blood combined leucine-isoleucine concentration and the ratio to other amino acids like alanine and phenylalanine.

MSUD Family Support Group

The Maple Syrup Urine Disease Family Support Group is an organization that provides support, resources, and education to those seeking information about MSUD. This organization hosts a biennial symposium for parents interested in support and information. In addition to the symposium, the MSUD Family Support Group also provides a newsletter that provides the latest information regarding research and treatment, family news and related topics.