Maple Syrup Urine Disease (MSUD): Causes, Forms, Symptoms, Diagnosis, Treatment, Nutritional Therapy, Complications, Prevention

Maple syrup urine disease (MSUD) is a metabolic disorder, which is inherited and runs in families. In this condition, there is an inability to breakdown certain components of proteins. Persons with this condition, pass urine having a characteristic smell like that of maple syrup; hence the name.

Maple syrup urine disease (MSUD) is a genetic disorder and is caused by changes or mutations in some genes that signal the body to produce certain enzymes necessary for digestion and metabolism. Having such defective genes may result in either non-production or mal-functioning of the related enzymes.

Maple syrup urine disease (MSUD) is inherited from parents, when both parents have one defective gene. The parents may not necessarily have the disease but they can be carriers; which means that they can pass the defective gene to their children.

In Maple syrup urine disease (MSUD), there occurs some defect in a particular gene responsible for the breakdown of some protein components. These components are amino acids, namely, leucine, isoleucine and valine. As these proteins are not broken down, they accumulate and form keto- acids, thus mounting up chemicals in the blood.

This accumulation can affect the brain and its functional capabilities. If left untreated in infants, it can even lead to encephalopathy and progressive neuro-degeneration.

Maple syrup urine disease (MSUD) can affect different individuals in a different way depending on the defect and therefore, is seen in mild to severe forms. These are typically characterized as classic, intermediate, intermittent and other rare forms of Maple syrup urine disease (MSUD). These forms show variations in ages, degrees of enzyme activity and severity of the condition.

The symptoms vary based on the forms of Maple syrup urine disease (MSUD).

• Symptoms Of Classic Maple Syrup Urine Disease Or Classic MSUD– It is the commonest form seen in neonates in early days of life. Those who are breastfed may exhibit symptoms by the second week of their life. Early symptoms include lethargy, weak sucking, poor feeding, vomiting, poor weight gain, irritability, high-pitched cry and irregular sleep patterns. Clinical findings like alternate increased and decreased muscle tone, seizures, urine smelling like maple syrup may be noted.
• Symptoms Of Intermediate Maple Syrup Urine Disease Or Intermediate MSUD– It is rare as compared to the classic form. The clinical features may include neurological deficiencies, varying degrees of developmental delays, seizures, feeding issues, poor growth and urine or sweat smelling like maple syrup.
• Symptoms Of Intermittent Maple Syrup Urine Disease Or Intermittent MSUD– It is another common form of MSUD. Symptoms may be seen a little later after the newborn stage; they may have fairly normal amino acid metabolism. Symptoms can be particularly seen during periods of stress or infection. These symptoms include lethargy, seizures, ataxia and may even lead to coma if left untreated.
• Symptoms Of Thiamine-Responsive Maple Syrup Urine Disease Or Thiamine-Responsive MSUD– It is a rare form and seems to be responsive to treatment with Thiamine (Vitamin B1). Symptoms similar to intermediate form of MSUD may be seen in infancy.
• Symptoms Of E3-Deficient Maple Syrup Urine Disease Or E4-Deficient MSUD– This is a very rare form and appears similar to intermediate MSUD with additional lactic acidosis. Children with this form may also have other deficiencies and errors of metabolism.

Maple syrup urine disease (MSUD) is diagnosed by detecting elevated levels of the 3 amino acids that are not metabolized properly. Investigations performed to detect these include

• Plasma amino acid test
• Urine amino acid test

Newborn screening is done for early diagnosis.

Timely medical treatment can help to prevent undesirable complications. The primary aim is to reduce the excess accumulation of the amino acids in the blood. Intravenous glucose combinations are initiated, which will promote the utilization of the accumulated amino acids. Additional dietary support may be considered to avoid the intake of those amino acids which cannot be metabolized.

The basic aim of nutritional therapy is to restrict the intake of those 3 amino acids, particularly leucine, without compromising the nutrients required for the infant’s growth and development. Commercial formulas and foods, with specific requirements may be prescribed. Vitamin B1 or thiamine may also be administered for a specified period, in order to verify thiamine responsiveness, which may prove to be helpful.

If Maple syrup urine disease (MSUD) is not diagnosed correctly in time or if it is left untreated, it can lead to severe consequences and even be fatal. Metabolic crises can occur if the amino acid concentrations suddenly rise; can have rapid progression of symptoms and can lead to neurological damage. Symptoms like increased lethargy, irritability, vomiting and loss of alertness can be suggestive of metabolic crises.

If left untreated, it can lead to complications like seizures, affected blood flow to the brain or coma. Neurological damage, excessive muscle tightness and intellectual retardation can be some of the complications that can even lead to death.

Persons having this condition and under treatment, need to follow-up with the physician and monitor the amino acid levels at regular intervals. Dietary advice should be followed as prescribed, for example, foods free from or low in protein or specially formulated foods. This is Maple syrup urine disease (MSUD) special diet and needs advice and monitoring from a nutritional expert.

Genetic counseling must be considered by couples having a family history of this genetic disorder. Prenatal diagnosis can also be performed by using techniques to detect amino acid levels in amniotic fluid. Newborn screening tests for early identification and advanced tests for confirmation may be performed and prompt treatment can be initiated.

With regular followups and careful monitoring of the amino acid levels, a child with Maple Syrup Urine Disease can lead a normal healthy life.  In some cases certain complications like metabolic crisis may develop.

In such instances it is always better to inform the physician beforehand of any classic symptoms of Maple Syrup Urine Disease so that immediate treatment can be started and such complications may be prevented.