Some newborns are born with maple syrup urine disease (MSUD), a rare metabolic illness. It is brought on by a flaw in the enzymes that digest some amino acids.
As part of newborn screening, the majority of newborns in the United States have their blood checked for MSUD. This enables medical professionals to begin treatment—typically with a particular diet—immediately to help avoid issues.
My 10-month-old baby smells like syrup—why?
This fact sheet contains details on MSUD. Some of these facts might not directly relate to your child because every child is unique. For certain kids, some treatments might be advised, but not for others. Both their main physician and a metabolic physician should monitor every child with MSUD.
WHAT IS MSUD?
“Maple syrup urine disease” is referred to as MSUD. Its delicious maple syrup-like odor in the urine of untreated newborns inspired the name. One kind of amino acid problem is this one. Protein, a substance that makes up numerous components of every cell in the body, contains specific amino acids that people with MSUD have difficulty digesting. Hormones, enzymes, hair, and antibodies are a few items that contain proteins. Amino acids, which come in 20 various varieties, are the building blocks of proteins. What form and function a protein has is determined by the arrangement of these amino acids within it. The instructions needed to create a single protein are stored in each gene.
Disorders of the Amino Acids: Acid disorders (AAs)
These are a collection of uncommon inherited diseases. Certain amino acids—the building blocks of protein—cannot be digested by people with problems of amino acids. The body accumulates these amino acids as well as other harmful chemicals. This may have detrimental implications on learning, development, and health. are a category of uncommon genetic traits that one inherits from their parents. The majority of characteristics, including eye color and hair color, are inherited genetically from one’s parents. They result from enzymes. a molecular catalyst for chemical processes. For instance, stomach enzymes hasten the process of breaking down food. Each enzyme can take part in a variety of chemical processes without altering or depleting itself. that are ineffective. Amino acids, which are smaller building components, are used to make proteins. Proteins are composed of tiny molecules called amino acids. Only 20 of the more than 100 distinct amino acids are used by our body to create all of its proteins. The order of amino acids in a protein is determined by our genes. It is determined by this sequence how the protein is shaped and what purpose it fulfills in the body. These amino acids must be processed by a variety of enzymes before being used by the body. People with amino acid problems are unable to digest some amino acids because of missing or malfunctioning enzymes. These amino acids then accumulate in the body and cause issues along with other harmful compounds. Various amino acid diseases have different symptoms and treatments. The same amino acid problem can affect different people differently. See the info sheets for each individual condition related to amino acids. Both men and women can develop amino acid abnormalities, which are inherited in an autosomal recessive way.
WHAT CAUSES MSUD?
Protein from meals is divided into smaller pieces called amino acids so that the body can use it. The amino acids are subsequently modified by certain enzymes so that the body can utilize them.
The most prevalent form of MSUD, known as “classic MSUD,” is brought on by a lack of a class of enzymes called “branched-chain ketoacid dehydrogenase” (BCKAD). This enzyme group’s role is to digest three distinct amino acids named leucine. One of the twenty amino acids that go into making protein. Since the body cannot produce it, it must be consumed through diet. All foods that contain protein contain it. isoleucine One of the twenty amino acids that go into making protein. Since the body cannot produce it, it must be consumed through diet. All protein-containing meals contain it, and valine One of the twenty amino acids that go into making protein. Since the body cannot produce it, it must be consumed through diet. It can be found in all protein-containing foods. These amino acids build up in the blood and cause issues when they cannot be broken down.
Branched-chain amino acids, or BCAAs, are the names given to leucine, isoleucine, and valine.
These amino acids resemble tree branches chemically in their structure. Three of the BCAAs are leucine (leu), valine (val), and isoleucine (ile). They can be discovered in all protein-rich foods. Meat, eggs, milk, and other dairy products contain significant amounts. Due to its “tree-like structure,” smaller amounts can be found in flour, cereal, and several vegetables and fruits. They can be discovered in all protein-rich foods. Meat, eggs, milk, and other dairy products contain significant amounts. Flour, cereal, as well as various vegetables and fruits, contain smaller quantities.
IF MSUD IS NOT TREATED, WHAT PROBLEMS OCCUR?
There are numerous varieties of MSUD. The most prevalent kind, “classic MSUD,” can be fatal and needs to be treated right away to avoid significant health issues. Other varieties of MSUD, such as the “intermediate” and “intermittent,” are less severe. These milder varieties are less prevalent. This fact sheet provides details on traditional MSUD.
The first time a baby is fed protein, usually soon after birth, the symptoms begin. Some of the initial signs include:
- lack of appetite
- poor, weak
- slim down
- cry that is loud
- urine that has a burnt sugar or maple syrup odor
Children with MSUD experience periods of illness known as metabolic crisis. Low blood sugar and a buildup of harmful chemicals in the blood are the two main contributing factors to this significant medical illness. Poor appetite, sickness, vomiting, diarrhea, excessive drowsiness, irritability, and altered behavior are signs of a metabolic crisis. Breathing issues, convulsions, comas, and occasionally even death, can happen if not treated. People with specific metabolic diseases experience metabolic crises more frequently (some fatty acid oxidation disorders, amino acid disorders, and organic acid disorders). They are frequently brought on by conditions including illness or infection, going for extended periods without eating, and, in certain circumstances, vigorous activity. The following are some of the initial signs of a metabolic crisis:
- extreme slumber
- In a bad mood
If untreated, more symptoms may appear:
- instances when muscular tone A certain degree of tension in our muscles is required for us to maintain our posture and manage our motions. This stress is known as “muscle tone People with hypotonia have too little tension in their muscles and appear “floppy. People who have hypertonia experience problems with their muscles being too tight and inflexible in their joints and muscles. goes back and forth between being hard and floppy
- expansion of the brain
- These are also known as “fits” or “convulsions.” A person experiences seizures, which cause them to lose consciousness and motor control. It could also result in uncontrollable movements. There are several causes of seizures. A metabolic crisis, brain damage, infections, and metabolic abnormalities are a few of the causes.
- Metabolic acidosis is characterized by elevated blood levels of acidic chemicals.
- When acidic substances accumulate in the blood, this occurs. Rapid breathing, disorientation, and severe tiredness may be a result. If untreated, it could result in shock, a coma, or even death.
- An individual cannot be roused from this sleep-like state. People that are unconscious are in comas. Numerous factors can put a person in a coma. Untreated low blood sugar (hypoglycemia), which can often result in death, and a metabolic crisis are two causes.
A metabolic crisis frequently has the following signs:
- following a prolonged period of fasting
- during an infection or illness
- amid anxiety-provoking situations like surgery
Damage to the brain can happen if it is not treated. Intellectual difficulties or spasticity may result from this This is muscle stiffness and an increase in reflexes. Increased muscle tone is the cause. The muscles and joints become abnormally tight or stiff as a result. Some infants go blind. Most infants with classic MSUD die within a few months if they are not treated.
WHAT IS THE TREATMENT FOR MSUD?
Your baby’s physician will collaborate with a metabolic physician This is a physician or medical geneticist with specialized education in the identification and management of metabolic diseases. They frequently work in big hospitals or universities. to look after your youngster, along with a dietitian.
To avoid intellectual deficits and major medical issues, prompt treatment is required. Most kids must consume a diet that is extremely low in protein and a particular medical formula. As soon as you learn that your child has MSUD, you should begin the diet and the formula. Your nutritionist This person has received specialized instruction in nutrition and food. A registered dietician (RD) has obtained the required education and has qualified on the national exam. Working with a trained dietitian is crucial if your child has a metabolic issue. For patients with metabolic problems or other particular needs, they assist in developing balanced meal plans. may develop a diet for your child that has the ideal ratio of protein, nutrients, and energy.
The following therapies are frequently suggested for kids with MSUD:
1. Pharmaceutical Mix
Children frequently receive a specific medical formula in place of milk in addition to a low-protein diet. This mixture supplies them with the vitamins, minerals, and protein they require while assisting in maintaining acceptable BCAA levels.
Your dietician and metabolic specialist will advise you on the best type of formula to use and how much to take.
2. Consume foods low in branched-chain amino acids.
The items that make up the diet are very low in BCAAs, which are amino acids present in protein. As a result, your child must refrain from eating items high in protein including cow’s milk, ordinary formula, meat, fish, cheese, and eggs. Additionally containing BCAAs, regular wheat, dried beans, almonds, and peanut butter are to be avoided or consumed in moderation.
Many fruits and vegetables only contain trace levels of BCAAs and can be consumed in moderation.
Other medicinal foods are available, such as rice, pasta, and special low-protein flours that are created just for MSUD sufferers. For medical formula and other specialized medical foods, some states provide financial assistance, while others mandate private insurance coverage.
The ideal eating regimen for your child will be chosen by your metabolic specialist and nutritionist. The precise strategy will rely on a number of factors, including the age, weight, and overall health of your child. Over time, your dietician will adjust the diet. Any dietary adjustments should be carried out with the assistance of a dietitian.
The MSUD diet must be used as a lifetime treatment. When children don’t adhere to the diet, they run the danger of experiencing episodes of metabolic crisis.
Thiamine pills can frequently benefit kids with a unique form of MSUD called “thiamine-responsive MSUD.” Thiamine may also help some kids with classic MSUD. One kind of vitamin B is this. Grains, pork, beans, seeds, and nuts all contain thiamine. It is essential for converting food into energy. If your child needs to take thiamine supplements, ask your doctor. Use only supplements after consulting your doctor, please.
the procedure of diagnosing an illness in someone who doesn’t seem to have it (non-symptomatic or asymptomatic). Finding the disease in its earliest stages is the aim of tracking. amounts of BCAA
To check their amino acid levels, your child will have routine blood testing. Depending on the findings of the blood test, the diet and formula may need to be modified.
5. When any ailment first appears, contact your physician.
Even a little sickness can trigger a metabolic crisis in kids with MSUD. When your child exhibits any of the following, contact your doctor straight away to avoid complications:
- excessive drowsiness or low energy
- a disease or infection
- the fever
- changes in behavior or personality
- difficulty walking or issues with balance
Even if they are not hungry, children with MSUD should consume extra carbs and fluids while sick since they run the risk of experiencing a metabolic crisis. Children who are ill might not feel like eating. If they are unable to eat or exhibit symptoms of a metabolic crisis, they may require hospital treatment.
Consult your metabolic doctor to determine whether you need to include a special travel letter with care instructions for your child.
6. Transplanting the liver
Surgery for a liver transplant is an optional therapy for MSUD patients. The liver is where the BCKAD enzyme that causes MSUD is found. As a result, some kids with MSUD have had liver transplant surgery (liver removal and donor liver replacement) to alleviate their MSUD symptoms.
The major surgical operation of a liver transplant carries some hazards. To keep their bodies from rejecting the donor liver, people who have received a liver transplant must take medication for the rest of their lives. However, MSUD symptoms are eliminated in patients who have a successful liver transplant.
Before having surgery, there are a lot of things to think about, so you should talk to your child’s doctors in great detail.
WHAT HAPPENS WHEN MSUD IS TREATED?
Children with MSUD can generally lead healthy lives with typical growth and development with immediate and ongoing treatment. Intellectual difficulties and brain damage can be avoided with early therapy.
However, attention deficit hyperactivity disorder is more likely to develop in kids with MSUD.
Children who are especially hyperactive are the subject of this. These kids having a hard time staying still. They move considerably more restlessly and erratically than usual. Some hyperactive kids require treatment. Even after a liver transplant, individuals may benefit from medication, behavior therapy, or a combination of these treatments for attention deficit hyperactivity disorder (ADHD), anxiety, and depression. At this point, it’s unclear why this is the case.
Even after receiving medication, some kids still have episodes of metabolic crisis or brain enlargement. Recurrent metabolic crises in children increase the risk of lasting brain damage. This may result in intellectual deficits, learning difficulties throughout life, or spasticity.
WHAT CAUSES THE BCKAD ENZYMES TO BE ABSENT OR NOT WORKING CORRECTLY?
Genes instruct the body to produce different enzymes. Three genes are present. a section of DNA that includes instructions for producing a particular protein (or part of a protein). On chromosomes are the genes. Chromosomes and the genes they contain are inherited from one parent to the next. Variants, which are mistakes in the DNA that makes up a gene, can cause diseases. that may result in DBT, BCKDHB, and MSUDBCKDHA. Each of these genes is present in two copies in every person. One of these genes had variations (changes) in both of the copies in MSUD patients. Because of these genetic variations, which are modifications to a person’s DNA. Gene variations can occur and have an impact on a gene’s functionality. There are various types of variations; they might be benign, which don’t cause problems, pathogenic, which can, and of unknown relevance. The term “variants” has taken the place of “mutations,” which refers to a malfunction or lack of production of the BCKAD enzymes.
HOW IS MSUD INHERITED?
MSUD is an autosomal recessive condition. Both males and girls are equally impacted by it.
Both functional copies of a gene required to produce the BCKAD enzymes are defective in MSUD patients. Each parent passes one defective MSUD gene to their offspring.
Rarely do parents of children with MSUD also suffer the illness. Instead, each parent carries a single defective MSUD gene. They’re known as carriers. A individual who carries the single gene mutation responsible for an autosomal recessive condition (remember genes come in pairs). The condition has no effect on carriers. They can, however, convey the gene variation to their offspring. Two of these gene variations will cause the condition in offspring. The word “mutation” has been replaced with “variants.” Because their other copy of this gene is functioning properly, carriers do not suffer MSUD.
There is a 25% probability that the child will have MSUD in each pregnancy when both parents are carriers. Like the parents, there is a 50% probability that the child will also carry the gene. A 25% probability exists that the infant will have two functional genes.
pertaining to (or resulting from) genes and heredity, or the study of genes and heredity. Families with kids who have MSUD can get counseling. Your questions about the condition’s inheritance, options for subsequent pregnancies, and how to test additional family members can be answered by genetic counselors. Inquire with your physician about a genetic counselor referral. These are medical professionals with specialized knowledge of genetic disorders. They aid in families’ understanding of the transmission of genetic illnesses. People who have hereditary disorders in their families or who are worried that a child they are expecting may have one can benefit from the information and support provided by genetic counselors.
IS GENETIC TESTING AVAILABLE?
Blood can be used for genetic testing for MSUD. Genetic testing, also known as DNA testing, searches for modifications, also known as variations, in the genes that are responsible for MSUD.
Deoxyribonucleic acid (DNA), a molecule present in chromosomes, is a genetic information-carrying molecule. The four units (referred to as bases) that make up DNA are A, T, G, and C. All of the instructions necessary to create the proteins required by an organism are written in the bases’ order. A gene is a segment of DNA that contains the rules for making a particular protein. A mutation is a change in one or more of the DNA nucleotides that make up a gene. Certain health issues or illnesses can result from mutations that alter the protein’s instructions. Each parent gives their offspring half of their chromosomes, and with them half of their DNA instructions. These instructions are what trigger the inheritance of particular features, like eye or hair color. To diagnose your child, no testing is required. It can be useful for prenatal testing or carrier testing, which are covered below.
WHAT OTHER TESTING IS AVAILABLE?
By counting the branched chain amino acids in a blood sample, MSUD can be verified. A blood or skin sample can be used in an enzyme test to diagnose it. If you have inquiries concerning MSUD testing, consult your physician or genetic counselor.
CAN YOU TEST DURING A FUTURE PREGNANCY?
If your child has both gene mutations (variants), DNA testing might be done during upcoming pregnancies. Either CVS or amniocentesis is used to get the sample required for this test. This test is carried out during pregnancy. A tiny sample of fluid is drawn out of the sac that surrounds the fetus using a needle. The sample can be used to check the fetus for certain genetic diseases. Typically, amniocentesis is performed between 13 and 20 weeks of pregnancy to test for genetic disorders.
An enzyme test can be performed on cells if DNA testing is not helpful.
the smallest habitation. In multicellular organisms like humans, cells make up all the organs and tissues. They are also capable of living on their own, just like bacteria and other microbes. A cell must at the very least have a membrane around it, have DNA at some point throughout its existence, and be able to divide itself into two identical copies. within the fetus. The sample required for this test is once more acquired by either CVS This unique test is carried out very early in pregnancy. A tiny sample of the placenta is taken during CVS and tested. This sample can be used to check the fetus for specific genetic diseases. Between 10 and 12 weeks of pregnancy, CVS is typically performed. also amniocentesis.
Parents can decide whether to test their unborn child while still pregnant or after delivery. To reduce the likelihood that their future children may have MSUD, parents may also decide to adopt assisted reproductive technologies. A genetic counselor can discuss your options with you and provide information on prenatal or postpartum testing for your unborn child.
CAN OTHER MEMBERS OF THE FAMILY HAVE MSUD OR BE CARRIERS?
Older siblings and sisters of a baby with MSUD are unlikely to also have the illness if they are healthy and developing normally. You should speak with your metabolic physician or genetic counselor if you have any concerns about testing your other children.
Even siblings who do not have MSUD can nevertheless become carriers like their parents. Carrier testing should only be performed on adults, unless there are exceptional circumstances.
Your siblings have a 50% probability of being MSUD carriers if you are the parent of a child who has it. It’s crucial to inform other family members that they might be carriers. There is a little possibility that they run the risk of passing MSUD to their offspring.
Every state provides infant MSUD screening. On the other hand, if both parents are carriers, newborn examination a screening procedure that uses a tiny amount of blood drawn from a newborn’s heel to look for various illnesses. A positive or abnormal newborn screening result indicates that the infant’s blood had minute variations, and additional testing is required to determine whether the baby has a metabolic disease. The issue cannot be ruled out in a newborn baby based on the results. In this instance, in addition to neonatal screening, specific diagnostic testing should be carried out. the procedure of checking for sickness in someone who doesn’t exhibit any symptoms of it (nonsymptomatic or asymptomatic person). The purpose of screening is to identify diseases in their earliest stages. It is crucial that this testing be conducted as soon as possible, ideally around 24 hours of age.