What are the other Names for this Condition? (Also known as/Synonyms)

• Branched Chain Alpha-Ketoacid Dehydrogenase Deficiency
• Congenital Infantile Lactic Acidosis due to LAD Deficiency
• Lactic Acidosis due to Lipoamide Dehydrogenase Deficiency

What is Maple Syrup Urine Disease? (Definition/Background Information)

• Maple Syrup Urine Disease (MSUD) is a genetic disorder in which the body is unable to metabolize (process) certain proteins (amino acids). This causes an accumulation of the protein in the body, leading to brain damage in severe cases
• The affected individuals’ urine, smells like maple syrup; due to which the condition is known as Maple Syrup Urine Disease

Who gets Maple Syrup Urine Disease? (Age and Sex Distribution)

• The ‘Classic type’ is the most common and severe form of Maple Syrup Urine Disease; a condition that becomes evident immediately after birth
• Other types may manifest during infancy or childhood. Though they may be mild, they could still involve developmental delays and medical problems, if not addressed
• Both males and females are equally affected; there is no predilection towards any particular sex

What are the Risk Factors for Maple Syrup Urine Disease? (Predisposing Factors)

The risk factors for Maple Syrup Urine Disease include:

• MSUD runs in the families and hence, children born in families with a medical history of the condition are at risk
• Those having consanguineous partners/spouses have the greatest risk

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Maple Syrup Urine Disease? (Etiology)

• Both parents have to be affected with, or be carriers of the defective genes, for their offspring to be affected with Maple Syrup Urine Disease; a feature known as autosomal recessive pattern of inheritance

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected). 

• Individuals with MSUD cannot breakdown the proteins leucine, isoleucine, and valine. As a result, there is a dangerously high level build-up of these proteins in the body, leading to a rapid deterioration brain damage, resulting even in death, if the condition is not treated
• Physical stressors, like starvation, fever, and infection, can worsen the damage

What are the Signs and Symptoms of Maple Syrup Urine Disease?

The infant may appear normal at birth; however, symptoms appear within 3-4 days. Signs and symptoms of Maple Syrup Urine Disease are:

• Poor feeding, lack of energy (lethargy)
• Vomiting
• Poor muscle tone (hypotonia)
• Developmental delay
• Backward arching of head and heels (opisthotonus)
• Sweet smelling urine; due to accumulation of proteins, which smell like maple syrup
• If left untreated; slowly the infant child will develop seizures, go into a coma stage, and die

How is Maple Syrup Urine Disease Diagnosed?

Maple Syrup Urine Disease is diagnosed by:

• Physical exam with evaluation of family medical history of the newborn
• Plasma amino acid test: A blood sample drawn from the baby’s heel detects high leucine levels
• Urine amino acid test
• Urine smell; which is like maple syrup or burnt sugar
• Ear wax may be examined for smell; it is similar to maple syrup smell, which may not be always true

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Maple Syrup Urine Disease?

The complications from Maple Syrup Urine Disease include:

• Seizures
• Coma

How is Maple Syrup Urine Disease Treated?

The treatment methods to address Maple Syrup Urine Disease include immediate and long-term measures:

• When diagnosed in an acute state, treatment of the condition involves a protein-free diet consisting of sugars, fat, and fluids, given intravenously
• Depending on the severity of the disorder, the healthcare provider may recommend dialysis to remove excessively accumulated proteins from the body
• Long term treatment measures include: Consulting a dietician to develop a feeding plan, careful and periodic monitoring of blood chemistry, and life-long special diet that avoids the proteins valine, leucine, and isoleucine

How can Maple Syrup Urine Disease be Prevented?

• Currently there are no specific methods or guidelines to prevent Maple Syrup Urine Disease genetic condition
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assessing the risk before planning children
• Active research is currently being performed to explore the possibilities for  treatment and prevention of inherited and acquired genetic disorders
• However, with strict diet control (a diet devoid of the proteins leucine, isoleucine, and valine), the affected individuals can live a healthy life with a normal lifespan, devoid of any neurological complications

What is the Prognosis of Maple Syrup Urine Disease? (Outcomes/Resolutions)

• If left untreated, newborns with Maple Syrup Urine Disease have a poor prognosis, with developmental delays. They may also develop brain damage, have seizures and go into coma, leading to death, within a few months of birth
• Even with strict diet control, factors like fever, infection, and starvation, can cause a worsening of the condition, calling forth for close monitor during such periods

Additional and Relevant Useful Information for Maple Syrup Urine Disease:

Gene therapy is projected as a potential future management tool for Maple Syrup Urine Disease.