MSUD (maple syrup urine disease) is a hereditary metabolic illness. Your body is unable to break down specific amino acids due to the condition.
After your body digests protein from diet, amino acids are what remain. Amino acids are processed by enzymes so that they may be used to sustain all of your body's activities. If any of the required enzymes are missing or faulty, amino acids and their metabolites, known as keto acids, accumulate in your body. As the concentrations of these compounds rise, they can cause:
- Neurological harm
- Coma
- Life-threatening circumstances
The body lacks an enzyme known as BCKDC in MSUD patients (branched-chain alpha-keto acid dehydrogenase complex). The BCKDC enzyme breaks down three essential amino acids known as BCAAs: leucine, isoleucine, and valine (branched-chain amino acids). BCAAs may be found in protein-rich meals such as meat, eggs, and milk.
MSUD, if left untreated, can develop serious physical and neurological difficulties. MSUD can be managed with dietary changes. Blood tests can be used to track the effectiveness of this approach. Early detection and intervention increase the likelihood of long-term success.
WHAT ARE THE TYPES OF MSUD?
MSUD is also referred to as:
- BCKDC deficiency
- branched-chain ketoaciduria
- branched-chain ketonuria I
- branched-chain alpha-keto acid dehydrogenase deficiency
MSUD is classified into four subtypes. All of these conditions are inherited genetic illnesses. They differ in terms of enzyme activity, severity, and the age at which the disease manifests itself.
- Classic MSUD: This is the condition's most prevalent and severe type. This type of individual has minimal, if any, enzyme activity – roughly 2% or less of normal activity. Symptoms begin to appear in neonates within a few days following birth. When the infant's body begins to digest protein from feedings, the onset normally occurs.
- Intermediate MSUD: This is an uncommon variant of MSUD. Symptoms and beginning age vary widely. This kind of MSUD has a greater degree of enzyme activity than traditional MSUD — around 3 to 8% of normal activity.
- Intermittent MSUD: This kind does not interfere with normal physical or mental development. Symptoms normally do not develop until a kid is between the ages of one and two. It is a milder version of traditional MSUD. Individuals have substantial enzyme activity, ranging from 8 to 15% of normal activity. When a youngster suffers stress, sickness, or an unexpected increase in protein, the disease often begins.
- Thiamine-responsive MSUD: Large dosages of thiamine, or vitamin B-1, often treat this unusual variant of the illness. Symptoms often appear after infancy. Although thiamine can be useful, dietary limitations are often required.
WHAT ARE THE SYMPTOMS OF MSUD?
The following are some of the earliest signs of classic MSUD:
- Lethargy
- A lack of appetite
- An odor of maple sugar in earwax, perspiration, and urine
- Unusual sleeping habits
- Slimming down
- A lack of sucking ability
- Irritability
- Alternating periods of hypertonia (muscle stiffness) and hypotonia (muscle limpness)
- Crying with a high pitch
Intermediate and thiamine-response MSUD symptoms include:
- Seizures
- Deficits in neurological function
- Sluggish growth
- Delays in development
- Feeding issues
- An odor of maple sugar in earwax, perspiration, and urine
WHAT ARE THE CAUSES OF MSUD?
MSUD is an autosomal recessive genetic condition. All kinds of the illness are passed on from your parents. The four types of MSUD are caused by mutations or alterations in the genes encoding the BCKDC enzymes. When such genes are faulty, the BCKDC enzymes are not generated or function improperly. These gene mutations are passed down through your parents' chromosomes.
Parents of children with MSUD often do not have the condition and have one mutant gene and one normal gene for MSUD. Despite carrying the faulty recessive gene, they are unaffected by it. MSUD signifies that you acquired one faulty BCKDC gene from each parent.
WHAT ARE THE RISK FACTORS FOR MSUD?
According to the National Organization for Rare Disorders (NORD), MSUD affects both men and women equally (about 1 in 185,000 people).
Your chance of developing MSUD in any form is determined by whether your parents are carriers of the illness. If both parents are carriers, their kid is born with a:
- There is a 25% probability of acquiring two mutant genes and developing MSUD.
- There is a 50% probability of getting only one faulty gene and becoming a carrier.
- Each parent has a 25% probability of passing on one normal gene.
If you have two normal BCKDC genes, you cannot pass the condition on to your offspring.
When two parents inherit the recessive gene for BCKDC, one of their offspring may get the condition while the other children may not. These offspring, however, have a 50% probability of being carriers. They may also be at risk of having a kid with MSUD later in life.
WHAT ARE THE COMPLICATIONS OF MSUD?
Undiagnosed and untreated MSUD complications can be severe, even deadly. Even newborns on a treatment plan might have episodes of acute disease, known as metabolic crises.
When there is a rapid and severe increase in BCAAs in the system, metabolic crises ensue. If left unchecked, the problem might have catastrophic physical and neurological consequences. A metabolic crisis is typically indicated by:
- Excessive exhaustion or lethargy
- Lack of vigilance
- Irritability
- Vomiting
When MSUD is not diagnosed or metabolic crises are not treated, the following serious problems might occur:
- Seizures
- Brain swelling
- Insufficient blood flow to the brain
- Metabolic acidosis is a condition in which the blood contains a high concentration of acidic chemicals.
- Coma
When these circumstances exist, they can lead to:
- Serious neurological injury
- Intellectual handicap
- Blindness
- Spasticity, also known as uncontrollable muscular tightness
- Life-threatening problems can develop over time and lead to death, especially if left untreated.
HOW IS MSUD DIAGNOSED?
According to the National Newborn Screening and Genetics Resource Center (NNSGRC), every state in the United States screens babies for MSUD as part of their newborn screening program, which is a blood test that screens for more than 30 diseases.
It is crucial to detect MSUD before birth in order to prevent long-term harm. When both parents are carriers and their child's MSUD test results are negative, further testing may be recommended to confirm the findings and avoid the onset of symptoms.
A urine or blood test might be used to diagnose MSUD if symptoms appear beyond the neonatal period. A high quantity of keto acids can be detected in urine, and a high amount of amino acids can be detected in a blood test. An enzyme study of white blood cells or skin cells can also confirm the diagnosis of MSUD.
If you suspect you are a carrier of MSUD, genetic testing can determine whether you have one of the disease-causing faulty genes. During pregnancy, your doctor can utilize chorionic villus sampling (CVS) or amniocentesis samples to diagnose your baby.
WHAT ARE THE TREATMENTS FOR MSUD?
If your newborn is diagnosed with MSUD, seeking medical attention as soon as possible will help you prevent major medical complications and intellectual disabilities. The first step in therapy is to lower the amount of BCAAs in your baby's blood.
Typically, this entails intravenous (IV) injection of amino acids devoid of BCAAs, along with glucose for added calories. The therapy will increase the usage of the body's current leucine, isoleucine, and valine. At the same time, it will lower BCAA levels while providing sufficient protein.
In collaboration with a metabolic expert and a dietician, your doctor will develop a long-term treatment plan for your kid with MSUD. The treatment plan's purpose is to supply your child with all of the protein and nutrients he or she requires for optimal growth and development. The approach will also prevent too much BCAAS from accumulating in their blood.
HOW CAN MSUD BE PREVENTED?
MSUD is a hereditary condition, hence there is no way to avoid it. A genetic counselor can assist you in determining your risk of having a child with MSUD. If you or your spouse is a carrier of the illness, genetic testing can inform you. Before birth, DNA testing can detect the condition in a fetus.
CONCLUSION
MSUD children can enjoy busy, regular lives. Regular medical supervision and stringent food restrictions might help your child avoid difficulties. Even with diligent supervision, a metabolic crisis can occur. Inform your doctor if your kid develops any MSUD symptoms. The best outcomes can be obtained if therapy is initiated and maintained as soon as feasible.