A Guide for Understanding Maple Syrup Urine Disease (MSUD)

A GUIDE FOR FAMILIES WHO HAVE A CHILD WITH Maple Syrup Urine Disease

CONTENTS INTRODUCTION TO MAPLE SYRUP 03 Introduction to Maple Syrup Urine Disease 10 Your Child’s Growth and Development URINE DISEASE 03 What is MSUD? 11 Teaching Your Child Diet Management Your child has a condition called Maple Syrup Urine Disease, or MSUD for short. Children who have inherited this 04 MSUD: An Inherited Disorder 12 Feeding Problems condition cannot use the essential amino acids isoleucine 05 Types of MSUD 13 The Role of Family and Other Care Providers in (i-so-lu-seen) (ILE), leucine (lu-seen) (LEU), and valine Managing MSUD (vay-leen) (VAL) in a normal way. 05 Diagnosis of MSUD These amino acids are found in all foods that contain protein. 05 Symptoms of MSUD 13 Your Child’s Diet During Illness You will need to feed your child all the foods necessary for 06 Nutrition Support of MSUD 14 A Look to the Future normal growth and development, but only the amount of Figure 1. Amino acids are joined together like beads on a necklace to ILE, LEU, and VAL he can safely use. form protein. Enzymes act like scissors to remove amino acids from 07 International System of Measurement 15 Recipes Learning some medical terms in nutrition and genetics will protein. (Metric System) 17 Resources help you understand and manage your child’s diet better. 09 Checking Your Child’s Progress If you have any questions, write them down and ask the nutritionist (dietitian), nurse, or doctor at the metabolic clinic. WHAT IS MSUD? MSUD is an inherited disorder of amino acid metabolism. Proteins, which are made up of amino acids, are found in many parts of the human body, including hair, blood, skin, and muscles. Most foods contain protein. When we eat foods containing protein, this protein is split into amino acids during digestion. The amino acids are later put back together like beads on a necklace to form new protein. These new proteins are used to build and repair the body’s tissues. Twenty amino acids occur commonly in the human body and in the foods we eat. Three of these essential amino acids are ILE, LEU, and VAL. Because of their chemical structure, these amino acids are described as branched chain. They are frequently grouped together and called branched-chain amino acids (BCAAs). All foods with protein contain BCAAs. High-protein foods are dairy products, eggs, meat, poultry, nuts, soy products, seafood, seeds, nut butters, beans and peas. Fruits, grains, and vegetables have less protein, and so have less ILE, LEU, and VAL. These are allowed in the diet in measured Abbott provides this booklet to health care quantities. professionals to help them counsel families, and Splitting protein into amino acids requires a special to families to help them learn about MSUD substance that does the actual work. Think of the splitting substance as a pair of scissors snipping beads off a necklace © 2023 Abbott (Figure 1). The “scissors” are called enzymes (n-simes). 2 3

Dietary Protein and Body Protein is an even milder form of the disorder and the diet can be Mother’s Genes Father’s Genes more liberal. The final type of MSUD is called thiamine- responsive MSUD. Large doses of the vitamin thiamine are given to improve the enzyme activity. The diet may not have to be restricted in protein, or only slightly restricted. Your child’s genetic doctor will help you understand the type of Branched-chain Leucine Isoleucine Valine Builds up in untreated MSUD A B Normal Gene MSUD your child has. amino acids (BCAAs) MSUD Gene BCKD= Branched-chain alpha (α) DIAGNOSIS OF MSUD Transaminase Transaminase Transaminase ketoacid dehydrogenase complex C D TP ~ P = Thiamine pyrophosphate, Most states require all babies to be screened for MSUD and which is required for BCKD to other conditions before they are discharged from the hospital. function Sometimes the symptoms of MSUD appear quickly, before the Branched-chain α-Keto- α-Keto- α-Keto- Figure 4. Genetic inheritance of MSUD. newborn screen result is available. In the states that do not ketoacids (BCKAs) isocaproic acid β-methylvaleric acid isovaleric acid include MSUD in their newborn screening, many infants are Each parent of a child with MSUD has one normal ( ) and one diagnosed after they start showing symptoms of MSUD. altered (MSUD) ( ) gene. Each one of their offspring will have BCKD TP~P TP~P TP~P one gene from each parent and could have one of four gene sets If the initial screening tests show that a baby may have MSUD, (Figure 4). some doctors may hospitalize the infant to confirm diagnosis A child who receives gene set A inherits two normal genes so that treatment can be started sooner if the baby has MSUD. Breakdown Products of BCAA metabolism ( ). Her body will make enough BCKD to use ILE, LEU, and Additional blood is drawn for precise measurement of ILE, Figure 2. BCAA metabolism in MSUD. VAL normally. She will pass a normal gene on to each of her LEU, VAL, and BCKAs, and urine is obtained to determine the offspring. amount of BCAAs and BCKAs excreted. Once ILE, LEU, and VAL are split off food protein, they are A child who receives gene set B or C inherits one normal SYMPTOMS OF MSUD absorbed, changed, and used to help form many other useful BCKD not working. ( ) and one MSUD ( ) gene. His body will make enough BCKD Excessive BCAAs and BCKAs in blood and tissues affect the substances in the body. ILE, LEU, and VAL cannot be to use ILE, LEU, and VAL normally, but he can pass on the nervous system. An untreated infant may have some or all of used normally . MSUD gene to his offspring. A person with this gene set—one these symptoms: In MSUD, the enzymes or group of enzymes called branched- normal and one MSUD—is called a carrier. Being a carrier does α) ketoacid dehydrogenase (BCKD) are absent BCKD not working well. • Ketoacidosis chain alpha ( not affect the person’s health. You, as parents of a child with or not working properly. Some people, such as your child, do ILE, LEU, and VAL may not be MSUD, are carriers. Brothers and sisters of your child with • Degenerative or permanent brain injury (encephalopathy) not have any normally working BCKD, or do not have enough used efficiently. MSUD may also be carriers. • Poor feeding to handle all the BCAAs that are in the protein foods they eat. • Poor sucking In either case, ILE, LEU, and VAL cannot be used normally BCKD working. A child with gene set D has MSUD caused by the two MSUD • Apnea (transient cessation of breathing) and MSUD occurs. Figure 2 shows what happens in MSUD. ILE, LEU, and VAL used normally. genes ( ), one from her mother and one from her father. Her • Sleepiness (lethargy) body will not be able to use the ILE, LEU, and VAL in food • Vomiting Think of the situation as a traffic light (Figure 3). A green normally. She will also pass the MSUD gene on to each of her • Irregular muscle movement traffic light (normal BCKD) allows ILE, LEU, and VAL to be Figure 3. The BCKD traffic light. offspring. Your child with MSUD has this gene set. • Seizures used normally. A red light (no or too little BCKD) keeps ILE, The presence of high levels of ketoacids of ILE gives urine, LEU, and VAL from being used. If the light is stuck on red, a TYPES OF MSUD sweat, and ear wax the odor of maple syrup or burnt caramel, traffic jam occurs—BCAAs and ketoacids (BCKAs) increase MSUD: AN INHERITED DISORDER There are several types of MSUD. The type generally refers which is how the disorder got its name. (Figure 2) and cause the symptoms of MSUD. MSUD is a genetic disease inherited from both mother and to the amount of enzyme activity. In the most common type— If a person is not treated, these products build up in the blood father, just like other features, such as eye and skin color. classic—little or no enzyme activity is present. The amount The nervous system symptoms usually appear during the and spill into the urine and perspiration. People who have Genetic information, which determines each person’s of LEU, ILE, and VAL must be severely restricted in the diet. first week of life. Poor control or late diagnosis of MSUD may untreated MSUD have too much ILE, LEU, VAL, and BCKAs characteristics, is carried on pairs of genes in every body cell. Intermediate MSUD has a higher level of enzyme activity and result in some delay in development. in their blood. These genes serve as blueprints, or patterns. can handle a greater amount of BCAAs. Intermittent MSUD 4 5

Ketonex®-2 Amino Acid-Modified Medical Food is a Table 1. General Guide to Foods on BCAA-Restricted Diets medical food used in the dietary management of children Table 2. Metric to English Conversions and adults with MSUD. This product contains no BCAAs, so Metric English Foods That Are Not Allowed Foods That Are Limited Foods That May Be Eaten Freely BCAAs must be met by using food sources. Ketonex-2 is also well supplied with fat, carbohydrate, minerals, and vitamins. Solids Dairy products (cheese, milk, ice Breast milk, infant formulas, bread, Gumdrop candy, hard candy, Your nutritionist will tell you which of the Ketonex products 1 g (0.001 kg) = 0.035 oz cream, yogurt), soy milk and soy crackers, fruit, fruit juices, low- jelly, Kool-Aid®, lemonade, is right for your child. ® 28 g = 1 oz products, beans and peas, eggs, fish protein cereals, popcorn, potato lollipops, Popsicles , pure fat, pure Ketonex-1 and Ketonex-2 taste different from milk. Most 454 g = 1 lb and seafood, meat, nuts, nut chips, special low-protein foods, sugar, soda children and adults get accustomed to the flavors of the foods butters, poultry, seeds, tofu vegetables, vegetable juices that they eat. They may seem distasteful to you, but it is very 1000 g (1 kg) = 2.2 lb important not to show this to your child, either by word or action. Liquids NUTRITION SUPPORT OF MSUD eating these foods in the amounts needed to provide just 5 mL = 1 tsp A diet that reduces BCAA intake is used to prevent the enough BCAA does not provide enough protein to meet the One mother disliked the odor of the medical food so much 15 mL = 1 Tbsp developmental delay and other problems associated with child’s needs for growth. To get enough protein for growth that she made a face every time she gave it to her son. 60 mL = 1/4 cup untreated MSUD. This diet, which is different for each and not get too much BCAA, a special medical food that is Because of this, he refused the medical food for several days 240 mL = 1 cup person with MSUD, can lower the blood BCAA to a range high in protein and free of BCAA is necessary. until she and her family realized what was wrong. She said 1000 mL (1 L) = 4 1/4 cup (1.06 qt) that permits normal mental development and growth. later, “We changed our attitude to thinking this wonderful The special MSUD diet for your child is very important. To be sure your child is getting enough energy, protein, and diet will make it possible for our child to have a happy life.” To provide enough energy and adequate BCAAs, protein, adequate BCAAs for growth and development, the nutritionist carefully calculates the amount of each nutrient needed. Too Most children taking medical foods for MSUD like them system to the English system is given in Table 2. However, minerals, and vitamins, a diet restricting BCAAs is designed little BCAAs, protein, or energy can result in growth failure. IF they are started early and IF their family has a positive the best way to be sure your child is getting the proper just for your child to maintain proper BCAA blood levels and Frequent diet adjustments are necessary, especially during attitude. amount of BCAA is to weigh food on a scale that reads in growth. the first 6 months of life when babies grow rapidly. The grams. nutritionist or metabolic doctor will make these diet changes Flavorings such as Kool-Aid® Unsweetened Soft Drink Mixes, Many foods contain protein. Those foods also contain BCAA. based on your baby’s health, growth, BCAA intakes, and blood Wyler’s® Unsweetened Soft Drink Mixes, Mio Liquid Water Formula Preparation. Mix a 24-hour supply of formula at Therefore, the amounts of foods that contain protein must be levels of BCAAs. Enhancers, and concentrated fruit juices can be added to one time, or as instructed by your nutritionist. limited in your child’s diet. Table 1 is a general guide to foods Ketonex. Remember to count the added BCAAs if they are that are not allowed, foods that are limited, and foods that Ketonex®-1 Amino Acid-Modified Infant Formula With present in any of the flavorings. Tips for preparing formula: may be eaten freely if obesity is not a problem. Iron is an infant formula used to provide protein for infants • Always follow the instructions on the label and mix and toddlers. Ketonex-1 does not contain any BCAAs. Similac® Ketonex may be made into a paste and combined with some the formula according to the recipe provided by your Additional Therapies: Your metabolic doctor may Advance® Infant Formula with Iron, breast milk, or other allowed fruits, such as applesauce or other fruit purees, or nutritionist or metabolic doctor. recommend certain vitamins, minerals, and medications for intact protein must also be fed to provide the specific amount combined with instant pudding mixes. Check the label and be your child with MSUD. Common ones include: of BCAAs a baby needs for growth and development. Breast careful which pudding mixes you buy, as some contain more • Wash your hands and all supplies carefully before • Thiamine may help improve enzyme activity. milk is lower in BCAAs than infant formula or cow’s milk protein than others. preparing formula. • L-ILE may be supplemented in pure amino acid form if and can be used to supply the required BCAAs. The decision • Mix in the approved natural protein if recommended by deficiency is noted. to breastfeed should be discussed with your nutritionist and INTERNATIONAL SYSTEM OF your nutritionist or metabolic doctor. • L-VAL may be supplemented in pure amino acid form if metabolic doctor. The nutritionist or metabolic doctor will MEASUREMENT (METRIC SYSTEM) • Do not mix longer than indicated on the Ketonex label. deficiency is noted. tell you the exact amount you will need in addition to your The metric system is the International System of Requirements for ILE, LEU, VAL, Protein, and Energy. A child’s infant formula. Ketonex-1 is well supplied with fat, Measurement. It is used for all medical and scientific • Overmixing causes the fat emulsion to break. Separation child with MSUD who eats enough protein to grow properly carbohydrate, minerals, and vitamins. Supplemental minerals measures. of the formula mixture then occurs. Overmixing may also gets too many BCAAs. Foods high in protein are cheese, milk, and vitamins are not usually needed when the diet is followed add air that destroys vitamins A and C. soy milk, eggs, meat, poultry, fish, nuts, tofu, beans and peas, as directed. In the metric system, solids are weighed in grams (g) or • Refrigerate the prepared formula after mixing. Discard seeds, and nut butters. Foods low in protein include some kilograms (kg) and liquids are measured in milliliters (mL) any unused formua 24 hours after mixing because of grains, fruits, fats, vegetables, and sweets. On the other hand, or liters (L). A list of common conversions from the metric nutrient loss. 6 7

should burp your baby at least once during and again at the end types and amounts of food that your child is allowed, will be CHECKING YOUR CHILD’S PROGRESS of each feeding. Hold him upright against your shoulder or lay outlined. The nutritionist will help you work out a plan that Laboratory Tests. Because your baby grows rapidly during him face down on your lap and gently pat his back. meets your child’s needs and fits into the family budget and the first year of life, blood is tested frequently for BCAA lifestyle. content. Many doctors will ask for a blood sample once or DO NOT WARM THE BOTTLE IN THE MICROWAVE. Lists of foods make meal planning easier and help you be sure twice a week during your baby’s first 6 months, then once a Uneven warming may cause serious burns. your child’s nutrient needs are met. You will have time to week until 1 year of age. After 1 year of age, checking blood become familiar with the food lists and their nutrient content, levels and diet records may be decreased to every 2 to 3 weeks because foods will be added slowly to your child’s diet. if blood BCAA levels are well controlled. Introduction of Solid Foods. No baby is born with the ability Various methods are used to monitor the amino acid to swallow solid foods. The swallowing reflex develops at 2 to 3 When your child is older, you may need to use Free Foods (see and ketoacid levels in the blood and urine. Urine may be months of age. Before this time, the baby’s “tongue thrust” causes Table 1) to meet his energy needs. Free foods, which are high monitored for the presence of ketoacids. Home monitoring the tongue to protrude, making swallowing food difficult. Wait in energy and contain little or no BCAAs, must not replace using dinitrophenylhydrazine (DNPH) or Ketostix® strips ing to feed solid foods until the baby is 4 to 6 months old is best. prescribed foods nor be used in large amounts. If your child may be used as a way of detecting ketones in the urine. How Feeding time should be a pleasant experience for you and Ketonex-1 is similar to infant formula, and the amounts, as eats too many of these free foods, he may become overweight, often your child is tested will be determined by your baby’s your baby. well as the kinds of cereals, fruits, and vegetables prescribed, or the extra sugar may cause tooth decay. Special low-protein metabolic doctor or nutritionist. are about the same as for any baby. Your baby’s nutritionist or foods, including pasta, rice, crackers, cookies, and breads, • Always test the temperature of heated formula before metabolic doctor will advise you about when your baby should can be added to the diet. These foods will help to satisfy your Before taking a blood sample, you may be asked to accurately feeding by shaking a few drops on your wrist. start eating infant cereal and strained baby foods, and which child’s hunger. record your child’s total food and beverage intake. On a • Heating above 100° F (37.8° C) or adding hot water may foods to introduce. Guidelines for adding various foods to your form the clinic will provide, record the name of the food, the cause loss of vitamins A and C and lead to the Maillard baby’s diet are given in Figure 5. However, your nutritionist or Be sure to check with the nutritionist before exact amount in household measures (cups, teaspoons, or reaction—a reaction in which some amino acids bind with metabolic doctor may suggest different ages. Follow their advice. using any food that is not on the food lists provided. tablespoons) or in grams that your child ate, and the BCAA carbohydrate, making them unavailable to the child. content based on the food lists or information given to you by Feeding Your Infant. The way you feed your baby with At 7 to 8 months of age, your child may begin trying to eat foods the nutritionist. MSUD is the same as for any baby. The Ketonex-1 formula such as crackers, low-protein toast, or pieces of fruit without If you have any questions about the content of certain foods, Blood BCAA Levels. The amount of BCAA in the blood will be supplemented with breast milk or infant formula such help. At about 9 months of age, your child may begin self-feeding the nutritionist can calculate the nutrient composition of the is an indirect measure of how many BCAAs are present in as Similac Advance EarlyShield. The nutritionist may have using a spoon. food and help you include it in the diet plan if it is not too high body tissues. Of most concern is the brain, because too much you mix the two formulas together. The Ketonex-1 mixture If your 9- to 12-month-old child has never eaten without help, in BCAAs. ILE, LEU, VAL, and their ketoacids are harmful to brain stored in bottles in the refrigerator may be warmed before dip her fingers into the food to give her the idea of finger feeding. feeding. Later, you can teach her to pick up a spoon and help guide it to • Shake the formula mixture and pour into a bottle. her mouth. Putting your child on your lap to guide her hand may Age in Months be easier. Start with thick foods, such as mashed potatoes, since • Set a bottle in a pan of cold water on the stove and they will not slip off the spoon easily. 1 2 3 4 5 6 7 8 9 10 11 12 gradually warm it or run hot tap water over the bottle. Do not worry if your child does not eat all of the foods you • Never use a microwave oven to warm formula as this can measure out; just estimate what was not eaten, replace the Ketonex-1 plus Similac Advance with Iron or breast milk result in hot spots that can burn your baby. BCAAs with another food, and write it down. Strained cereals • Always test the temperature of heated formula before When your child is older, the differences between the BCAA- Strained fruits and vegetables feeding by shaking a few drops on your wrist. The formula restricted diet and the diets of other children will be greater. Very-low-protein foods should feel lukewarm. Your child with MSUD will require Ketonex all her life to Cup feeding • If the Ketonex-1 mixture drips freely, the nipple holes are provide most of her protein, mineral, and vitamin needs. Self-feeding finger foods the correct size. Shake the bottle well before feeding. Coarsely chopped foods To feed your baby, sit in a comfortable place, hold him in Diet Guide and Food Lists. You will be given guidance at each the curve of your arm, and keep the nipple filled with the clinic visit that spells out in detail what your child can eat. The Self-feeding spoon Ketonex-1 mixture so that air will not be swallowed. You amount and how to prepare the medical food mixture, and the Raw foods 8 Figure 5. Suggested timetable for beginning solid foods and self-feeding. 9

development. Because blood transports nutrients to the brain, YOUR CHILD’S GROWTH AND Toddlers. Toddlers, children from 1 to 3 years of age, have a the concentration of BCAAs in the blood will give the doctor DEVELOPMENT slow growth rate compared with that of infants. Toddlers may and nutritionist an idea of the amount of ILE, LEU, VAL, and gain 4 to 5 pounds (1.8–2.3 kilograms [kg]) a year, compared their ketoacids that might be in the brain. By 4 to 6 months of age, your baby’s birth weight will double. with the infants’ gain of 12 to 22 pounds (5.5–10 kg) per year. The child with MSUD who is kept on a controlled intake of Growth during this period involves changes in body form. Blood BCAA levels that are high may indicate that your child is BCAAs and whose diet supplies adequate nutrients should Legs lengthen and body fat decreases. Energy needs are eating more foods that are high in BCAAs than her body needs grow as well as a child without MSUD. decreased because of the slower growth rate. However, for growth. Illness, such as colds and flu, can also cause the During the second 6 months of life, the growth rate decreases. mineral and vitamin needs increase. body to break down its own protein, releasing BCAAs into the Your child may grow 1 inch (~ 2.5 centimeters [cm]) per month blood. When your child is not getting enough protein, because during the first 6 months and 4 inches (~ 10 cm) total during Toddlers seek independence and are very curious about of rapid growth or inadequate intake of the medical food, the the second 6 months of life. This normal decline in the growth their environment. Because toddlers want to do things for blood BCAA level may also rise. Initially during rapid growth, rate usually causes a decrease in appetite. themselves, encourage your child to feed himself. the blood BCAA level will decrease and then increase as the Preschoolers. Preschoolers also have a slow weight gain of body breaks down its own protein. Although the requirement for energy (calories) and protein 4 to 5 pounds (1.8–2.3 kg) per year. On the other hand, their A low BCAA level usually indicates that your child is not based on body weight decreases, the total daily requirement total energy needs are greater than those of toddlers. Because getting enough BCAAs in the diet. Sometimes to keep the for most nutrients increases with age. You will have to adjust your preschooler’s nutrient and energy needs are greater, the level of LEU low enough, ILE and VAL drop. The doctor may food choices accordingly to ensure that your child has an nutritionist may tell you to increase foods with a high nutrient prescribe ILE and VAL supplements to keep the BCAAs in adequate nutrient intake. The nutritionist will help you with content. These foods are packed with vitamins and minerals balance. This will help your child grow properly. food selections that are right for your child. and are energy dense. Clinic Visits. Because MSUD is a lifelong condition that could Weaning from Bottle to Cup. When the time comes to switch Let your preschooler make some decisions. For example, harm growth and development, you will be asked to bring from the bottle, your child may need extra attention, as any permit him to choose which cereal, fruit, or vegetable to eat. your child to the clinic frequently. If growth and development child would. Weaning takes patience, especially if your child Be aware that most preschoolers want to do things at their Some materials that you may find helpful are listed on page 17. are normal and blood BCAA concentrations remain within shows no interest in drinking from a cup or a glass. own speed. Be prepared to have your child spend so much Toddlers and Preschoolers. Permit your preschooler the treatment range, the frequency of clinic visits may be Begin offering Ketonex-1 from a cup when your child is time talking that little is eaten. This is normal behavior. to make food choices such as what fruit to eat for a fruit decreased with time. between 5 and 8 months of age. Some parents find a training Social Interaction at Mealtime. Mealtime is an important serving. Plan meals that have variety in color, texture, flavor, At clinic visits, your child may be given developmental, cup that has a lid and a spout to be very useful. part of every child’s social development and, whenever and preparation methods. A child who is involved in food physical, and neurological tests. Family interaction, which is possible, the family should eat together. Younger children can selection and preparation will be more interested in trying important to her development, may also be evaluated. The During weaning, your child may not want to take all of the learn how to feed themselves by watching older brothers and a new food. Involve your child in planning menus so he can clinic can address any questions or concerns you may have. prescribed Ketonex in liquid form. You may have to use more sisters. become familiar with foods allowed and excluded. Let him Diet changes will be made, if needed, and any questions you of it in instant puddings, cereals, fruits, and soups. Some of Make meals for your child with MSUD as similar as possible help with grocery shopping, setting the table, and preparing may have will be answered. the Ketonex can be mixed into a paste with fruits and fed by to the family’s meals. Menus for him can be planned from the food. spoon. those for the rest of the family. For example, whenever In addition to the metabolic specialist, you should have a local At about 3 to 4 years of age, children want to serve pediatrician or family doctor to provide required ongoing possible, use the same fruits and vegetables for everyone. The themselves. Teach your child the proper food portions. Your well-child care. Immunizations should be given at the usual ADDITIONAL WATER MUST BE OFFERED WHEN family’s help and support are very important to maintaining dietitian may provide you with a technique or way to count ® the child’s diet. protein that you can teach your child. times by this doctor, or you may obtain them from the health KETONEX IS FED AS A PASTE. department. Consult your child’s nutritionist. TEACHING YOUR CHILD DIET School Age. When your child reaches school age, she will MANAGEMENT become more independent in many aspects of her life and A child of 15 to 18 months may drink more medical food from a eating is one of them. As she begins to develop logic and math cup if he is given a small pitcher of Ketonex and is encouraged Explaining the diet to your child can begin by calling allowed skills, it is important she use these skills to understand the to pour it into a small cup without help. Many parents have foods “special” or “just for you.” From the time she is very diet. Encourage your child to help prepare the medical food found using brightly colored straws, special cups, or sports young, teach her to ask about unfamiliar foods before eating and calculate the amount of BCAAs in foods. As your child bottles to be good transitional tools to help wean a child from them. As your child grows older and is able to understand the gets older, she should understand what levels of BCAA are the bottle. concept of a missing or nonworking enzyme, explain MSUD. considered normal and the consequences of high BCAA levels. 10 11

Adolescence. Adolescence may be a difficult time for both the of your child’s nutrition needs. If refusal of the medical food THE ROLE OF THE FAMILY AND OTHER Feeding an ill child can be very difficult. Often a child with child and the parents, regardless of MSUD! The influence of continues to be a problem, the use of a feeding tube may need CARE PROVIDERS IN MANAGING MSUD fever is restless and loses appetite. The illness might also friends and the struggle for independence may make dietary to be considered. Parents carry the bulk of the responsibility for the diet. If include stomach upset, nausea, or even vomiting. A child may compliance a challenge. They may feel that MSUD makes them Refusing Solids. A child may experience normal variations in possible, try to share the responsibility, so both parents can become very dehydrated because of the high body temperature different from their friends. Eating out with friends is part appetite or taste for certain foods. Or, the prescribed amount of prepare and monitor the diet. Other children in the family, as and a lack of adequate fluid intake. of growing up. Help your child develop the skills for eating Ketonex may be too high and the energy in it is causing her to well as the child with MSUD, should learn about the diet as If you suspect a cold or virus, or if your child has a fever, it out, traveling, and “sticking” to the diet when not at home. lose her appetite. is important to call your pediatrician or metabolic doctor Sometimes teenagers with MSUD would rather tell people they soon as they are old enough to understand it. Older brothers are a vegetarian or vegan than explain about MSUD. Help your Toddlers and preschoolers periodically have one of two and sisters should be encouraged to be involved in feeding the immediately. Illness in a child with MSUD can be very serious. teenager deal with her peers and not be self-conscious that she characteristic feeding behaviors that cause parents concern. child with MSUD so they become familiar with foods allowed Your metabolic doctor or nutritionist will help you decide has MSUD. Finding a peer with MSUD through support groups They may decide to stop eating—go on a “food strike,” or they and excluded. Make sure they understand the importance of on how to manage it. Ask your nutritionist for a “sick-day can be a great comfort for a teen. Ask the clinic for resources may go on a “food jag.” the diet for their brother’s or sister’s health. Brothers and plan” to use during illness. A sick-day plan provides adequate and suggestions. During a food strike when your child refuses to eat, offer food sisters should not feel sorry for the child with MSUD because calories to meet energy needs and helps keep your child at usual mealtimes and if she refuses the food, take it away. she is on a special diet. Treat your child with MSUD as out of the hospital. Ask about beginning medication such as FEEDING PROBLEMS Allow only water between meals. She will become hungry and normally as possible. acetaminophen (Tylenol®) to reduce fever and fluids to prevent Parents may be tempted to treat their child as a “sick” child then eat. Remember that Ketonex supplies most of your Grandparents love to spoil their grandchildren! It may be dehydration. and not follow their usual patterns of child rearing. The child child’s nutrient needs, so her medical food should never be difficult for them as they sometimes feel the child with Here are some suggestions of things to do when your child is ill with MSUD is a normal child who needs to manage food intake restricted. MSUD is “missing out.” It is important that they understand with fever. carefully. Ask your child’s doctor, nutritionist, public health Do not give in to the food strike and offer free foods or foods the diet and become actively involved as much as possible. A • Do not force-feed food or Ketonex, especially if your child is nurse, or social worker for support and help if any of the that are not on the BCAA-restricted diet. The nutritionist can grandmother may be the ideal person to experiment with low- nauseated or vomiting. Soda crackers may be the only food following problems should occur. help you during this trying time, so do not hesitate to call. It is protein cooking and provide special low-protein treats. he will feel like eating. Encourage intake of any allowed Loss of Appetite. Loss of appetite can result from a variety also very important for both parents to support each other in Explain MSUD to relatives, friends, day-care providers, baby- foods your child is willing to eat. of causes, including illness; eating too many sweet foods or managing a food strike. If a child is allowed to eat foods not on sitters, and all teachers. They should become familiar with • Encourage your child to continue drinking his medical food desserts that satisfy the appetite and decrease the desire to eat her diet, blood ILE, LEU, and VAL levels will not be controlled. foods allowed and excluded and understand the importance of if he tolerates it. the foods prescribed; getting too much Ketonex, which may On a food jag, a child wants to eat the same food or foods for the diet. Give a list of the foods allowed and excluded to anyone • Offer Pedialyte® Oral Electrolyte Solution with added depress the appetite for other foods; or having a lower than long periods. If the foods are nutritious and are in the diet, who feeds your child and explain the list as well as the exact carbohydrate, such as dextrose or table sugar (3 Tbsp sugar normal blood BCAA level. Some children have a poor appetite there is no reason for concern. Remember that most of your menu. to 8 fl oz of Pedialyte); Pro-Phree®; non-cola carbonated despite adequate treatment and dietary management. In such child’s nutrient needs are supplied by Ketonex. beverages; sugar-sweetened carbonated beverages; Kool- cases, it may be necessary to use a feeding tube to ensure Tell everyone who cares for your child that even “just a little Aid®; Tang®; tea with sugar; vegetable broth; or fruit juices nutrition needs are met. Inappropriate Feeding Behavior. Inappropriate behaviors, bite” of a high-protein food is not allowed. Emphasize what can with some sugar added. Unusual Hunger. This may be an indication that the diet such as refusing to give up the bottle and/or difficulty in eating happen if your child does not stay on the diet. • Dilute the Ketonex mixture, or use liquid Jell-O® if it is needs to be adjusted. The amount of Ketonex may need to be solids, chewing, or self-feeding, may result from a variety tolerated. increased because the table foods prescribed are not satisfying of causes, including a delay in offering solid foods; delay in YOUR CHILD’S DIET DURING ILLNESS • Freeze any of the beverages listed and make into chipped needs. Providing low-protein foods is a great way to manage teaching the child to drink Ketonex by cup; or not allowing ice. Frequently feed small amounts of this chipped ice to hunger without increasing protein intake. the child to self-feed either with his fingers or a spoon. Always A body temperature greater than 98.6° F (37° C) or a rectal provide energy and prevent dehydration. keep a positive attitude and make feeding a pleasurable event. temperature over 100° F (37.8° C) is a fever. During a fever, the • As your child’s appetite improves, gradually return to the Refusing Medical Food. A child may refuse Ketonex because Try not to feed a child longer than necessary at mealtime to body’s rate of using food for energy speeds up. If extra energy usual diet plan. of normal variations in appetite, and this should not be of encourage self-feeding. Remember that small amounts of food is not supplied during illness, the body will break down its own concern, especially if average intake over a week is adequate. If are usually wasted when a child first learns to selffeed, but muscle and fat stores for energy. Muscle protein breakdown Emergency Letter. Individuals with MSUD should have an Ketonex is not offered regularly, a child may decide to refuse this is normal. Keeping food records will help your nutritionist needs to be prevented in children with MSUD, because it will emergency letter with them at all times. This letter provides it. Improperly mixed Ketonex can also be a cause—too much estimate your child’s intake. release too much BCAA into the blood. BCAA is then carried important information such as the name of the condition, water makes the volume too great; too little water makes the to the brain where it may have a harmful effect. Give your child explanation of symptoms, the importance of timely treatment medical food mixture too thick. A child may refuse Ketonex A child may be using his diet as a way of getting attention or extra low-protein foods, formula or fluids during illness. This and treatment strategies, and your metabolic doctor’s contact as an attention getting device, especially if he senses that his manipulating parents. If your child has any of these problems, extra food energy will decrease the amount of muscle protein information. In times of illness or stress that may require parents are anxious for him to drink the Ketonex mixture. call the nutritionist. The nutritionist will give you support and broken down for body energy. hospitalization, this letter can be presented. This letter can be Remember, Ketonex plays an important role in providing most offer suggestions to help solve the problem. provided by your metabolic team. 12 13

A LOOK TO THE FUTURE While there is no test that can determine if another child will RECIPES Continuing the Diet. MSUD is a serious health concern. be affected with MSUD before a pregnancy, prenatal testing Treating a child as early in life as possible helps to prevent may be possible during the early part of the pregnancy. A ® ® developmental delay and neurological damage. Not following couple may want to discuss and consider all their options with Kool-Aid -Flavored Ketonex -1 the MSUD diet may cause mental and nervous system damage their metabolic doctor and genetic counselor before having Yield: 8 fl oz at any age. Lifelong nutrition support must be adapted to each another pregnancy. 40 g Ketonex-1 person’s needs. Metabolic doctors and nutritionists provide If you decide to have another child, give yourselves time to 3 Tbsp, level, sugar1 ® support that will help your child have a normal, productive life. adjust to the special needs of the first child. Make sure you 1/4 tsp Kool-Aid or Wyler’s Unsweetened Soft Drink Mix Current research is looking at alternative treatment options for have learned diet management for your child with MSUD Add water (room temperature) to ingredients to make 8 fl oz. Mix in a MSUD, such as enzyme replacement, gene therapy, and liver before having another child. blender at lowest speed no more than 4 seconds. Or, shake briskly in a transplantation. However, until these therapies can be proven Offspring of a Person with MSUD. All children born to a closed container for 10 to 12 seconds. Serve chilled. effective and safe, dietary treatment for life is essential. person with MSUD will be carriers of the gene. As shown in Nutrient 1 fl oz 8 fl oz Figure 6, all offspring of a parent with MSUD ( ) and a parent Family Planning. MSUD occurs approximately one time who is normal ( ) inherit one normal ( ) and one MSUD ( ) Isoleucine, mg 0 0 in every 185,000 live births. In the Old Order Mennonite gene. Each one of their offspring will be a carrier. Leucine, mg 0 0 population, MSUD occurs in approximately 1 in 175 newborns. If a person with MSUD has children with a carrier for MSUD, Valine, mg 0 0 The chance that two carriers of MSUD will have a child with approximately one-half (50%) of their offspring will have Protein, g 0.75 6 MSUD is 1 in 4, or 25%, for each pregnancy (Figure 4). The MSUD and one-half (50%) will be carriers (Figure 7). Energy, kcal 42 336 chance that two carriers will have a child who is a carrier is 1 in 2, or 50%, for each pregnancy. Childbearing by Women with MSUD. For the woman with 1 Osmolality (concentration of particles in solution) may be too high if more sugar is added, which may cause bloating and diarrhea. MSUD, having children may cause problems. A major concern 2 The amount of drink mix may be varied according to taste preference. Before a couple who has a child with MSUD has any more for women with MSUD is the stress of the pregnancy on her children, they should take time to seriously think about the metabolic control. Nutritional requirements can rapidly change special parenting tasks that parents of a child with MSUD during the course of a pregnancy. Pregnant women must be must manage. Genetic counseling is recommended to review monitored carefully for their own safety, as well as the health the risks and to discuss several reproductive options that are of their baby. Successful pregnancies require careful diet ® ® monitoring during the prenatal, labor, delivery, and postpartum Kool-Aid -Flavored Ketonex -2 available before and during pregnancy. Yield: 16 fl oz periods. 40 g Ketonex-2 3 Tbsp, level, sugar1 1/2 tsp Kool-Aid or Wyler’s Unsweetened Soft Drink Mix2 Mother’s Genes Father’s Genes Mother’s Genes Father’s Genes Add water (room temperature) to ingredients to make 12 fl oz. Mix in a blender at lowest speed no more than 4 seconds. Or, shake briskly in a closed container for 10 to 12 seconds. Serve chilled. Nutrient 16 fl oz A B Normal Gene A B Normal Gene Isoleucine, mg 0 MSUD Gene MSUD Gene Leucine, mg 0 C D C D Valine, mg 0 Protein, g 12 Energy, kcal 308 Figure 6. All children of a person with MSUD and a person who doesn’t Figure 7. Approximately half of the children of a parent with MSUD 1 Osmolality (concentration of particles in solution) may be too high if more sugar is added, which may cause bloating and diarrhea. have MSUD will be carriers of MSUD. who mates with a carrier of MSUD will have MSUD. 2 The amount of drink mix may be varied according to taste preference. 14 15

RESOURCES ® Fruit Juice-Flavored Ketonex -2* Support Groups/Newsletters Med-Diet™ Laboratories, Inc. Yield: 8 fl oz 3600 Holly Lane, Suite 80 MSUD Family Support Group 20 g Ketonex-2 Email: [email protected] Plymouth, MN 55447 1 3 fl oz concentrated apple, grape, or orange juice Website: msud-support.org Phone: (800) 633-3438 (MED-DIET); Water (room temperature) to make 8 fl oz (763) 550-2020 Warm juice concentrate to room temperature. Place all ingredients in a Low-Protein Food Suppliers Fax: (763) 550-2022 blender and mix at lowest speed no more than 4 seconds. Or, shake briskly Email: [email protected] in a closed container for 10 to 12 seconds. Serve chilled. Canbrands Specialty Foods, Inc. Website: med-diet.com Nutrient Apple Grape Orange 3500 Laird Rd. Unit 4 PKU Perspectives Mississauga, ON, Canada L5L 5Y4 Lindon, UT 84042 juice juice juice Phone: (905) 829-6003 Phone/Text/Fax: (866) 758-3663 Leucine, mg 33 15 48 Email: [email protected] Email: [email protected] Website: canbrands.ca Website: pkuperspectives.com Isoleucine, mg 0 9 28 Valine, mg 6 13 41 Dietary Specialties Taste Connections, LLC Protein, g 6.5 6.7 8.5 8 S. Commons Rd. Phone: (310) 413-6499 Energy, kcal 257 276 251 Waterbury, CT 06704 Fax: (310) 318-8407 *Please check with your dietitian or doctor before using this recipe in infants. Phone: (888) 640-2800 Email: [email protected] Website: dietspec.com Website: tasteconnections.com Ener-G® Foods, Inc. ® 5960 First Avenue South Additional Tips for Flavoring Ketonex Medical Food Seattle, WA 98108 Phone: (800) 331-5222; (206) 767-3928 • Add chocolate or strawberry syrup. Fax: (206) 764-3398 • Mix Ketonex with fruit to make a “smoothie.” Email: [email protected] • Freeze flavored medical food into “slushies” or “popsicles.” Website: ener-g.com • Add dry Ketonex to pudding (lemon, tapioca, vanilla, etc) mixture. Prepare pudding with non-dairy creamer. Use low-protein food lists to calculate protein content of flavorings. Ketostix, Jell-O, Kool-Aid, Popsicles, Tang, Tylenol, and Wyler’s are not registered trademarks of Abbott Laboratories. 16 17

IMPORTANT PHONE NUMBERS Abbott Metabolic Medical Foods Nutritionist: ______________________________________________________ Fire: ______________________________________________________ 21 products to meet a wide range of nutrition Metabolic Doctor: ______________________________________________________ Hospital: ______________________________________________________ needs in more than 40 inborn errors of metabolism. Pediatrician: ______________________________________________________ Other: ______________________________________________________ Police: ______________________________________________________ ______________________________________________________ Your Path to Insurance Reimbursement Support Phenylketonuria (PKU) Maple Syrup Urine Disease Urea Cycle Disorders Abbott offers a reimbursement support program to help determine your coverage options for Abbott Metabolic products and will connect you with a supplier who can help get it delivered right to you door. Propionic and Glutaric Aciduria Type I STEP STEP STEP Methylmalonic Acidemia 1 2 3 How it Call We Help We Help with insurance determine connect you to works and prescriber’s available coverage suppliers who deliver information options products Tyrosinemia Isovaleric Acidemia and Homocystinuria Call To Get Started: 1-855-217-0698 (M-F, 8:30 a.m. to 5:00 p.m. EST) Disorders of Leucine Metabolism To learn more, visit pathway-plus.com Each health care provider is ultimately responsible for verifying codes, coverage, and payment policies used to ensure that they are accurate for the services and items provided. Providers should consult with the insurance plan for complete and accurate details concerning documentation for claims. Abbott Nutrition does not guarantee reimbursement by any third- Dietary Modification Hypercalcemia Ketogenic Diet Management Dietary Modification party insurance plan and will not reimburse physicians or providers for claims denied by third-party insurance plans. of Protein Carbohydrate Disorders of Carbohydrate and Fat 18 19

Use under medical supervision. Abbott Metabolic Medical Foods ® Ketonex is part of an extensive line of medical foods from ® Abbott, makers of Similac . Visit the AbbottStore.com for product information and purchasing. If you are a new patient, ask your health care provider to request a free starter kit to get you started on our product. © 2023 Abbott 20202996/January 2023 LITHO IN USA