Three amino acids are affected in the breakdown process by the uncommon and dangerous genetic illness known as maple syrup urine disease (MSUD): valine, isoleucine, and leucine. Meat, eggs, and dairy products are examples of foods high in protein that include these amino acids. High concentrations of these amino acids and their metabolites in the blood and urine can harm the brain and other organs if MSUD is left untreated.
One of the four genes—BCKDHA, BCKDHB, DBT, or DLD—mutates to develop MSUD. The three amino acids are broken down by the branched-chain alpha-keto acid dehydrogenase (BCKD) complex, which is made up of the enzymes encoded by these genes. The amino acids and their byproducts build up in the body and have harmful consequences when the BCKD complex is malfunctioning.
A person must inherit two copies of the faulty gene—one from each parent—in order to be afflicted with MSUD since the condition is autosomal recessive. A carrier is someone who is born with one copy of the faulty gene; they do not show any symptoms, but they can still convey the gene to their progeny.
The symptoms of MSUD vary depending on the type and severity of the condition. There are five main types of MSUD:
Conventional MSUD: The most common and serious kind of MSUD. In the initial few days of life, symptoms frequently include poor feeding, vomiting, lethargy, irritability, convulsions, a coma, and a distinctive maple syrup odor in the urine, sweat, or earwax. If left untreated, classic MSUD can result in brain damage, developmental delays, and fatality.
A less severe kind of MSUD is called intermediate MSUD. The condition can cause poor development, learning challenges, muscular weakness, and bouts of metabolic crisis brought on by sickness, infection, or stress. These symptoms might manifest later in infancy or childhood. A metabolic crisis can be fatal and result in acidosis, coma, and dehydration.
A moderate kind of MSUD is called intermittent MSUD. Only rare occurrences of metabolic crisis—which mostly happen during times of fasting, sickness, infection, or stress—usually result in symptoms. People with intermittent MSUD grow and develop normally in between bouts.
Thiamine-responsive MSUD: This unusual kind of MSUD reacts well to high-dosage vitamin B1 (thiamine) therapy. Similar symptoms to intermittent or moderate MSUD can be avoided or lessened by supplementing with thiamine.
E3-deficient MSUD: This is an uncommon kind of MSUD that affects not only the three amino acid breakdown but also other metabolic pathways that depend on the DLD gene-encoded enzyme dihydrolipoamide dehydrogenase (E3). Lactic acidosis, neurological issues, and liver malfunction are among the symptoms.
MSUD can be diagnosed by a combination of clinical signs, biochemical tests, and genetic tests. The diagnosis may include:
Newborn screening: A blood sample from the heel is used to measure the levels of amino acids and other chemicals in order to test most babies for metabolic abnormalities such as MSUD and other conditions soon after delivery. Additional testing is required to confirm the diagnosis and determine the type of MSUD if the screening test results are positive.
Blood and urine tests: These tests measure the levels of amino acids and their byproducts, such as alpha-keto acids and organic acids, in the blood and urine. High levels of these substances indicate MSUD or another metabolic disorder.
Genetic tests: These tests analyze the DNA and look for mutations in the BCKDHA, BCKDHB, DBT, or DLD genes. Genetic tests can confirm the diagnosis of MSUD, identify the type of MSUD, and determine the carrier status of family members.
The treatment of MSUD aims to prevent or reduce the accumulation of amino acids and their byproducts in the body, and to avoid or manage episodes of metabolic crisis. The treatment may include:
Dietary control is the cornerstone of MSUD therapy. It entails limiting protein consumption and consuming foods or supplements that include the necessary amino acids and other nutrients but lack excess valine, leucine, and isoleucine. The kind and quantity of protein that is permitted is determined by the individual's age, weight, and MSUD type. A nutritionist and a metabolic specialist must closely evaluate and modify dietary plans.
Medication: Certain individuals with MSUD may benefit from taking drugs that increase the activity of the BCKD complex or other enzymes involved in the metabolism of amino acids, such as lipoic acid, biotin, or thiamine. Depending on the kind and severity of MSUD, medication may be utilized in addition to or instead of nutritional control.
A liver transplant is a surgical operation in which a healthy liver from a donor is used to replace the sick liver. MSUD can be cured with a liver transplant since the new liver can break down amino acids and create the normal BCKD complex. But having a liver transplant is a difficult and dangerous process that calls for immunosuppression for the rest of one's life and ongoing monitoring. People with severe or uncontrolled MSUD who do not react to previous therapies are often the ones who are eligible for it.
There is no way to prevent MSUD, as it is a genetic disorder that is present from birth. However, there are some steps that can be taken to reduce the risk or severity of complications, such as:
Prenatal diagnostic: To find out if their unborn child has MSUD, parents who are carriers of the disorder might choose to get a prenatal diagnosis. Chorionic villus sampling (CVS) and amniocentesis are two methods for making prenatal diagnoses that entail removing a sample of tissue or fluid from the placenta or amniotic sac and analyzing it to look for genetic mutations. Prenatal diagnosis can assist parents in making decisions about whether to end the pregnancy or continue it, as well as in preparing for the delivery and care of their child.
Newborn screening: As early identification and treatment might avoid or lessen the harm caused by the illness, all infants should undergo screening for metabolic disorders, including MSUD, immediately after delivery. The infant should be sent to a metabolic expert for confirmation and therapy if the screening test results are positive.
Frequent monitoring and follow-up: Individuals with MSUD should undergo routine blood and urine testing to track their amino acid and byproduct levels and modify their treatment plan as necessary. They should also see their nutritionist, metabolic expert, and other medical professionals on a regular basis to evaluate their general health, development, and growth.
Reducing triggers: Individuals with MSUD should minimize or stay away from everything that might start or exacerbate a metabolic crisis episode, including fasting, disease, infections, stress, surgery, and anesthesia. In addition, they have to have a medical alert bracelet or necklace that lists their illness and the medications they should and shouldn't take, as well as an emergency plan. If they experience any of the signs or symptoms of a metabolic crisis, such as vomiting, lethargy, or coma, they should get medical help right once.
