Maple syrup urine disease (MSUD) is a rare genetic disorder characterized by an inability to process certain amino acids due to a deficiency of specific enzymes.
Both the parents of a child are usually carriers and impose no health complications in their bodies; however, they typically pass the affected gene to their child.
The symptoms start to appear within 1-2 days of life.
The urine odor in this condition smells like maple syrup, which is why it is called maple syrup urine disease (MSUD), also called BCKDC disease, branched-chain ketoacid dehydrogenase deficiency, or branched-chain ketonuria-1.
MSUD is common among Mennonites compared to other populations.
What is maple syrup urine disease?
Maple syrup urine disease (MSUD) is a hereditary metabolic or autosomal recessive disorder that decreases the metabolism of specific amino acids, thus, depleting the energy needed for the proper functioning of the body.
Usually, the three specific branched-chain amino acids, Lucien, isoleucine, and valine, are obtained from the protein from food when ingested and metabolized by an enzyme called BCKD complex (Branch Chain alpha-keto acid Dehydrogenase).
Unfortunately, people with MSUD cannot break down these amino acids in protein obtained from food due to a deficiency of BCKD.
Commonly, the symptoms of MSUD become apparent in infants and children, and infants are indicated at early ages of life or within 1-2 days after birth when they start taking breast milk or formula milk.
However, if left untreated or not managed on time, it can continue throughout life, leading to life-threatening complications.
MSUD is rare but highly associated with infants rather than older children or adults, and it affects males and females equally.
In addition to MSUD, many other diseases can occur due to a deficiency of specific enzymes in the body.
For example, 5-alpha reductase deficiency that affects male sexual development, resulting in ambiguous genitalia and rudimentary prostate.
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Signs and symptoms
The following are the symptoms of MSUD:
- Appetite loss
- Weight loss
- Poor sucking ability and water retention leading to peripheral edema
- Severe headache
- Pancreatitis
- A unique odor of maple sugar (sweet-smelling) in urine, earwax, and sweat
- Sleeplessness
- Muscle rigidity (hypertonia) or limpness (hypotonia)
- Variation in muscle tones
- Abnormal movement of muscles
- Convulsions
- Respiratory failure
- Fits/Seizures
- Poor growth
- Coma
- Brain damage
- Difficulty in breathing
- Vomiting
- Restlessness/ Irritability
- Delay in development & growth
- Some neurological deficiencies
Early and nonspecific signs of maple syrup urine disease, such as irritability, increased sleep, and loss of appetite, appear within 1-2 days after birth.
When the infant is 4-6 days old, signs of encephalopathy, including lethargy, breathing difficulties, and sweet maple syrup odor in urine, start to appear.
If left unmanaged, an affected infant may lead to life-threatening complications like cerebral edema, respiratory failure, and coma within 1-2 weeks after birth.
Risk factors
The main risk factor for developing maple syrup urine disease (MSUD) is the presence of mutated genes in both the parents of a newborn.
The type of MSUD present in anyone depends on the parent carrier, if any. And if both have, there may be the risk of receiving:
- Only one defective gene or being a carrier with the 50% risk
- Two mutated genes with a 25% risk and having MSUD
- One normal gene from both parents with a chance of 25%.
Two normal genes for BCKD show no risk of passing the disease to the children from the parents.
However, if both parents have recessive genes, there may be a chance of having MSUD in their new children, so such children have a 50% chance of having a disease or being a carrier.
What causes MSUD?
An autosomal recessive genetic disorder is inherited from the parents to the child. MSUD is due to the gene mutation, or changes, that associated BCKDC enzyme.
Those defective genes do not let the BCKDC produce or, if produced, do not work correctly.
And the mutation of genes is also inherited from the parents on chromosomes. The parents with an MSUD child do not have the disease, but they carry recessive defective genes and possess one regular and one mutated gene in children.
So every child with MSUD has one mutated gene for the enzyme BCKDC from each parent; however, the parents do not have the disease in them.
When to see a doctor?
If any symptom of metabolic crisis occurs in the child, such as:
- When the child’s urine or sweat smells sweet
- Poor appetite or a fever
- Tiredness than usual or sluggish behavior of the baby
- Repeated diarrhea
- Recurrent vomiting
- Indigestion of emergency diet or supplement
Immediately contact the metabolic team in the hospital and move to the emergency and accident department. Keep all the records of the child with you for MSUD. The immediate treatment at a hospital is intravenous fluid administration. However, if you are facing the following issues:
- Difficulty in urination
- Infrequent urination
- Facing difficulty in emptying the bladder
- Blood in semen or urine
- Painful urination or feel burning
Visit the doctor as these are not the symptoms of MSUD but for disease associated with the Prostate gland.
Diagnosis
The following are the main diagnostic methods used for diagnosing MSUD.
Newborn screening
Infants with maple syrup urine disease are usually diagnosed with newborn screening programs soon after birth.
During the screening, a special machine measures the levels of leucine, isoleucine, and/or valine in the infant. High levels of these branch-chain amino acids indicate MSUD.
In addition, a newborn blood spot screening test is done for five-day-old babies (the baby’s heel is pricked to collect blood drops to test).
Urine and blood testing
If symptoms appear after birth, the diagnosis can be made by:
- Urine analysis: Detect high levels of keto acids in the urine, known as ketonuria. Ketonuria is a quick way to learn about metabolic diseases like MSUD.
- Blood test: Detects high levels of specific amino acids in the blood.
- Enzyme analysis of white blood cells and skin cells.
Genetic testing
During pregnancy, genetic testing can be done to know about the carrier to diagnose the baby affected with MSUD with amniocentesis and CVS (Chorionic Villus Sampling). Moreover, fetal DNA testing can also help diagnose MSUD before birth.
However, if both parents are carriers, but the child is negative for MSUD during newborn screening, further confirmatory tests can be done to ensure the absence of disease.
Treatments
Initial treatments to treat MSUD include the following regimens.
Intravenous (IV) fluids administration
To lower the level of BCAAS in the person’s blood, amino acids which contain no BCAAs and combine with glucose and insulin for energy are administered by the intravenous route.
This will help to utilize the BCAAs that already exist in the body. Thus, a protein needed by the body is available, and BCAA is also reduced at the same time.
Nasogastric feeding tube/parenteral nutrition
Through the nose, the required nutrient and amino acids the body tolerate are provided.
Usually, parenteral nutrition involves feeding an amino-acid mixture without leucine, isoleucine, and valine via an NG tube.
Dialysis or Hemofiltration
In dialysis or hemofiltration, plasma is filtered and returned to the body to reduce the BCAAs level. It is usually recommended in infants with severe disease.
During the acute and early phases of severe MSUD, the infant is primarily monitored for the following signs and symptoms:
- Swelling in the brain
- Acid accumulation
- Infection
Permanent treatment
A liver transplant is a permanent solution for people with maple syrup urine disease. However, it is only considered in adults who experience recurrent symptoms despite following strict dietary management.
After a successful transplant, they require no dietary restriction, as the liver produces enzymes to break down the BCAAs.
Moreover, they possess no symptoms and have no cognitive issues but still carry the defective gene, which may pass to offspring, so genetic counseling is still required.
Lifestyle changes to improve symptoms
Long-term treatment of MSUD involves lifelong daily dietary management, as explained below.
Dietary management for infants
Although breast milk alone contains high amounts of leucine, isoleucine, and valine, it is still encouraged to breastfeed your infant. However, it is essential to keep the blood levels of these amino acids at an acceptable level. MSUD infant formulas are available in the market that contains carbohydrates, fat, vitamins, minerals, and essential and non-essential amino acids, except leucine, isoleucine, and valine.
Dietary management for toddlers and growing children
Natural proteins contain high amounts of leucine, isoleucine, and valine; that’s why low-protein diets and synthetic proteins (that don’t contain these amino acids) are the mainstays of dietary management. Low-protein diets prevent the build-up of excessive leucine, isoleucine, and valine in the blood.
Supplementation with protein substitutes and low-protein solids
Protein substitutes are usually required during the weaning period as the baby is at growing age. To compensate for the restriction of a high-protein diet, supplementation with powdered amino acids can provide the necessary amino acids required for growth. Sometimes, a dietitian may introduce low-protein solids in children experiencing mild symptoms.
Other lifestyle changes
Other lifestyle changes include regular monitoring of amino acids level in the blood, staying well-hydrated, and avoiding physical stress.
Moreover, carers should also be aware of the cardinal signs and symptoms of maple syrup urine disease while caring for their child.
If there are any of the above-mentioned signs, it is recommended to consult a pediatrician immediately because MSUD can rapidly lead to associated complications.
A dietitian and a metabolic specialist work together to ensure the better treatment and management of MSUD in the child.
The treatment plan will help avoid the excessive accumulation of BCAAs in the blood and provide enough nutrients and protein for the body’s normal functioning.
What foods to eat and avoid with maple syrup urine disease?
There are certain foods you should avoid with maple syrup urine disease and other green-go foods that can be taken without caution.
Foods to eat with maple syrup urine disease:
- Eat fruits and vegetables. This includes both fresh and tinned-frozen fruits such as apples, apricots, grapes, guava, kiwi, pineapple, dragon fruit, papaya, raspberries, blueberries, watermelon, and dates.
- Babies should be introduced to low-protein finger food such as toast (low-protein), parboiled carrots, and fruits such as peaches, strawberries, bananas, and sweet potato chips.
- Furthermore, chutneys, treacle, jams, and marmalade are also low in leucine, isoleucine, and valine. That’s why such foods can also be taken in MSUD.
Foods to avoid with maple syrup urine disease:
There are certain foods that should be avoided in MSUD because those foods contain high amounts of protein. These foods include the following:
- The meat of lamb, beef, pork, ham, bacon, chicken, and duck.
- Fish of all kinds, including shellfish, fish fingers, and fish cakes.
- Milk and milk products, including yogurt, dairy products, cream, and chocolate.
- White and brown bread, peanut butter, nut spreads, pasta, cakes, and biscuits.
- Gelatine-containing jellies and sweets.
However, most foods that are restricted in MSUD also have low-protein alternatives that a child can take.
Conclusion
Maple syrup urine disease is a rare but inherited metabolic disorder due to the deficiency of enzyme complex BCKD (branched-chain alpha-keto acid dehydrogenase) needed to metabolize branched-chain amino acids.
The building up of those BCAAs in the blood and urine causes serious issues, such as a physical or mental disability in children if untreated.
However, with early diagnosis and treatment and better management with a pediatric consultant and dietitian, MSUD can be prevented, and the child may have a typical everyday life.
The prevention and treatment include intravenous fluid and special supplements that avoid branched-chain amino acids (BCAAs).
Dietary prevention includes avoidance of foods containing branched-chain amino acids. A high protein diet is highly restricted in maple syrup urine disease.
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