A Guide for Understanding Disorders of Leucine Catabolism (DLC)

A GUIDE FOR FAMILIES WHO HAVE A CHILD WITH Disorders of Leucine Catabolism

CONTENTS INTRODUCTION TO DISORDERS OF 03 Introduction to Disorders of Leucine Catabolism 11 Your Child’s Growth and Development LEUCINE CATABOLISM 03 What Is a DLC? 12 Teaching Your Child Diet Management Your child has been diagnosed with a disorder of leucine catabolism (lu-seen ka-tab-o-lism), or DLC for short. Children 04 Disorders of Leucine Catabolism: An Inherited Disorder 12 Feeding Problems who have inherited this condition cannot use the essential amino 05 Types of Disorders of Leucine Catabolism 13 The Role of Family and Other Care Providers in acid leucine (lu-seen) (LEU) in a normal way. LEU is found in Managing a DLC all foods that contain protein. You will need to feed your child 06 Diagnosis of a DLC all the foods necessary for normal growth and development, but 06 Nutrition Support of a DLC 14 Your Child’s Diet During Illness only the amount of LEU he can safely use. 08 International System of Measurement (Metric System) 15 A Look to the Future Learning some medical terms in nutrition and genetics will Figure 1. Amino acids are joined together like beads on 16 Recipes help you understand and manage your child’s diet better. If you a necklace to form protein. Enzymes act like scissors to 09 Checking Your Child’s Progress have any questions, write them down and ask the nutritionist remove amino acids from protein. 17 Resources (dietitian), nurse, or doctor at the metabolic clinic. WHAT IS DLC? A DLC 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. LEU is one of these amino acids. LEU is an essential amino acid that is important for growth. All foods with protein contain LEU. High-protein foods include dairy products, beans and peas, eggs, fish and seafood, meat, poultry, nuts, soy products, seeds, and nut butters. Fruits, grains, and vegetables have less protein and, therefore, have less LEU. These are allowed in the diet in measured quantities. Splitting protein into amino acids requires a special substance that does the actual work. Think of the splitting substance as a pair of scissors snipping beads off a necklace (Figure 1). The “scissors” are called enzymes (n-simes). Abbott provides this booklet to health care professionals to help them counsel families, and to families to help them learn about disorders of leucine catabolism. 2 © 2023 Abbott 3

Once LEU is split off from food protein, it is absorbed, Think of the situation as a traffic light (Figure 3). A green within first few weeks of life. A “sweaty-feet” odor of the changed, and used to form many other useful substances traffic light (normal enzyme) allows LEU to be used normally. Mother’s Genes Father’s Genes blood and urine are noted. Some infants also exhibit severe in the body. In a DLC, the enzymes needed to rid the body A red light (no or too little enzyme) keeps LEU from being acidosis seizures, high ammonia levels (hyperammonemia), of the products of the breakdown of LEU are absent or not used. If the light is stuck on red, a traffic jam occurs—LEU low platelet count in the blood (thrombocytopenia), low working properly. People with a DLC, such as your child, and organic acids increase in the blood and tissues and cause number of white blood cells (neutropenia), low number of do not have any normally working enzyme or do not have symptoms of a DLC. red and white blood cells and platelets (pancytopenia), and enough to handle all the LEU that is in the protein foods they If a person is not treated, LEU and organic acid also spill into A B Normal Gene low calcium levels (hypocalcemia). eat. In either case, LEU cannot be used normally and LEU or the urine and perspiration (sweat). DLC Gene • “Chronic Intermittent” IVA children are normal at the products from its breakdown build up as organic acid and birth. During the first few years of life, they may develop other toxic (poisonous) substances. Enzyme not working. C D episodes of vomiting, metabolic acidosis, and excessive This excess keeps another important substance, coenzyme A LEU cannot be broken down. LEU tiredness (lethargy). The characteristic “sweaty-feet” odor (CoA), from working and causes the symptoms of a disorder and organic acids build up in the is typically present, and temporary hair loss (transient of leucine catabolism (Figure 2). blood and urine. Figure 4. Genetic inheritance of DLC. alopecia) is usually seen. Episodes may begin as early as 2 weeks of age, and the frequency of attacks seems to Enzyme not working well. decrease with age. Infections tend to trigger the episodes, Dietary protein L-Leucine Tissue protein LYS and TRP may not be You, as parents of a child with DLC, are carriers. Brothers as does illness and an excessive intake of protein. broken down efficiently. and sisters of your child with DLC may also be carriers. Additional Therapies. The goal of nutrition management GDH working. A child with gene set D has DLC caused by the two DLC genes of IVA is to avoid too much isovaleric acid in the blood LYS and TRP used normally. ( ), one from the mother and one from the father. Her body and urine while supplying energy, protein, vitamins, and Breakdown products do not will not be able to use the LEU in food normally. She will also minerals needed for normal growth and development. An 2-Keto-isocaproic acid build up. pass a DLC gene on to each of her offspring. Your child with a LEU-free medical food with the addition of a low-protein Figure 3. The disorders of leucine catabolism (DLC) traffic light. DLC has this gene set. diet (restricting LEU) is recommended. Your metabolic doctor may also recommend carnitine and/or glycine Isovaleryl-CoA DISORDERS OF LEUCINE CATABOLISM: TYPES OF DISORDERS OF LEUCINE supplementation. Carnitine and glycine help the body get rid AN INHERITED DISORDER CATABOLISM of toxic metabolites that build up in the body as well as help to IVA prevent possible deficiencies. DLCs are genetic disorders inherited from both mother There are four disorders of leucine catabolism considered to be and father, just like other features such as eye and skin branched-chain organic acidurias. The name of the deficiency 3-Methylcrotonyl-CoA Carboxylase Deficiency (meth- color. Genetic information, which determines each person’s generally refers to the enzyme affected. Dependent upon which ill-crot-o-nil Co-A car-box-ill-ase), or 3-MCC, is a deficiency 3-Methylcrotonyl-CoA characteristics, is carried on pairs of genes in every cell in the disorder of leucine catabolism your child has will determine in 3-methylcrotonyl CoA, blocking the body’s ability to break body. These genes serve as blueprints, or patterns. treatment methods. Your metabolic doctor and nutritionist will down LEU (Figure 2). Children typically have normal growth 3-MCC discuss which treatment method is best for your child. and development until they have an acute episode between Each parent of a child with a DLC has one normal ( ) and one 6 months and 3 years of age. Symptoms have also been 3-Methylglutaconyl-CoA altered DLC ( ) gene. Each one of their offspring will have Isovaleric Acidemia (I-so-val-air-ic a-cid-ee-mia), or IVA, is reported in the neonatal period and also as late as adulthood. one gene from each parent and could have one of four gene a deficiency of isovaleryl-CoA dehydrogenase (i-so-val-air-ill Symptoms typically occur after an infection and may include sets (Figure 4). Co-A dee-hi-drog-en-ase) (IVD), that prevents LEU from being poor muscle tone (hypotonia), or coordination, poor feeding, 3-Methylglutaconic used in the body. Because LEU cannot be used normally, LEU vomiting, excessive tiredness (lethargy), developmental Aciduria A child who receives gene set A inherits two normal genes ( or the products from its breakdown build up as isovaleric acid delay, or symptoms resembling Reye’s syndrome (low blood 3-Hydroxy-3-methylglutaryl-CoA ). Her body will make enough enzyme to use LEU normally. and other toxic (poisonous) substances. This excess keeps sugar [hypoglycemia], high ammonia levels in the blood HMG-CoA lyase She will pass a normal gene on to each of her offspring. another important substance, coenzyme A (CoA), from working [hyperammonemia], metabolic acidosis, elevated liver A child who receives gene set B or C inherits one normal ( ) and causes the symptoms of IVA. A characteristic feature of enzymes [transaminases], and seizures). and one DLC ( ) gene. His body will make enough enzyme IVA is a distinctive odor of sweaty feet. This odor is caused by Acetoacetic acid Acetyl-CoA Mevalonic acid to use LEU normally, but he can pass on the DLC gene to his the build-up of isovaleric acid in affected individuals. There are Additional Therapies. Nutrition management of 3-MCC Figure 2. Metabolic pathway for LEU. The black boxes show offspring. A person with this gene set—one normal and one two different types of IVA—acute and chronic. deficiency involves management of the initial infection that the site of where there could be an enzyme that doesn’t work, DLC—is called a carrier. Being a carrier does not affect the • “Acute” IVA infants appear normal at birth but develop triggered the 3-MCC symptoms, correction of carnitine causing the noted disorders. person’s health. poor feeding, vomiting, diarrhea, and drowsiness (lethargy) deficiency (if present), and possible LEU restriction. 4 5

Nutrition management may include an LEU-free medical movement (psychomotor abnormalities), seizures, and food paired with a low-protein diet (restricting LEU). Your nervous system impairment. Reye-like symptoms, including Table 1. General Guide to Foods on LEU-Restricted Diets metabolic doctor may also recommend carnitine and/or low blood sugar (hypoglycemia), acidosis, and high ammonia Foods That Are Not Allowed Foods That Are Limited Foods That May Be Eaten Freely glycine supplementation. Carnitine and glycine help the body levels (hyperammonemia), have also been reported. get rid of toxic metabolites that build up in the body as well Additional Therapies. The goal of treatment during Dairy products (cheese, milk, ice Breast milk, infant formula, bread, Gumdrop candy, hard candy, as help to prevent possible deficiencies. acute episodes is prevention of body protein breakdown cream, yogurt), soy milk and soy crackers, fruit, fruit juices, low jelly, Kool-Aid®, lemonade, protein cereals, popcorn, potato ® 3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency (catabolism) by carbohydrate administration and correction products, beans and peas, eggs, fish chips, special low-protein foods, lollipops, Popsicles , pure sugar (3-hi-drox-ee 3-meth-ill-glue-tar-ill-Co-A lie-ase), also of the acidosis. The effect of long-term nutrition management and seafood, meat, nuts, nut butters, vegetables, vegetable juices and fat, soda known as HMG-CoA lyase deficiency. This deficiency of this rare disorder has not been established. Nutrition poultry, seeds, tofu not only blocks the body’s ability to break down LEU, but management may include an LEU-free medical food paired also prevents the body from making ketones (key-tones), with a low-protein diet (restricting LEU). Your metabolic Requirements for LEU, Protein, and Energy. A child vitamins. Supplemental minerals and vitamins are not usually which are used for energy during periods without food doctor may also recommend carnitine supplementation. with a DLC who eats enough protein to grow properly gets needed when the diet is followed as directed. (fasting). HMG-CoA lyase deficiency symptoms may include Carnitine helps the body get rid of toxic metabolites that build too much LEU. Foods high in protein are cheese, milk, soy vomiting, excessive tiredness (lethargy), metabolic acidosis, up in the body as well as help to prevent possible deficiencies. milk, eggs, meat, poultry, fish and seafood, nuts, beans and I-Valex®-2 Amino Acid-Modified Medical Food With Iron low blood sugar (hypoglycemia), high ammonia levels DIAGNOSIS OF A DLC peas, seeds, and nut butters. Foods low in protein include is a medical food used for the dietary management of children (hyperammonemia), and an enlarged liver (hepatomegaly), some cereals, grains, fruits, fats, vegetables, and sweets. and adults with a DLC. I-Valex-2 contains no LEU, so LEU frequently triggered by an illness or fasting. Infection, high Most states require all babies to be screened for disorders Eating these foods in the amounts needed to provide just must be met by using other food sources. Your nutritionist protein intake, and prolonged fasting can lead to metabolic of LEU catabolism and other conditions before they are enough LEU does not provide enough protein to meet your will tell you which medical food is right for your child, as decompensation, resulting in low blood sugar with a small discharged from the hospital. In cases where DLCs are not child’s needs for growth. Depending on your child’s protein well as which foods and how much of each your child can eat. amount or no ketones produced (hypoketotic hypoglycemia), tested on newborn screening, an individual may be diagnosed tolerance, a special medical food that is high in protein and I-Valex-1 and I-Valex-2 must be used under the supervision and an increase in several organic acids. The inability to after showing symptoms of the condition. free of LEU may be required. of a physician. produce ketones in response to fasting can cause severe low If the initial screening tests show that a baby may have a To be sure your child is getting enough energy, protein, and I- Valex-1 and I-Valex-2 taste different from milk. Most blood sugar. DLC, additional blood and urine are collected for more adequate LEU for growth and development, a nutritionist children and adults get accustomed to the flavors of the foods Additional Therapies. Paired with a low-protein diet precise measurements that will confirm the diagnosis. Some carefully calculates the amount of each nutrient needed. Too that they eat. They may seem distasteful to you, but it is very (restricting LEU intake), additional therapies include doctors may hospitalize the infant to confirm diagnosis so that little LEU, protein, or energy can result in growth failure. important not to show this to your child, either by word or prompt attention to illness, decreased fat intake, carnitine treatment can be started sooner if the baby has a DLC. Frequent diet adjustments are necessary, especially during action. Your child may refuse the medical food just because supplementation, and avoidance of fasting. The goal of long- the first 6 months of life when babies grow rapidly. The you appear not to like it. term nutrition management is to prevent low blood sugar, NUTRITION SUPPORT OF A DLC nutritionist or metabolic doctor will make these diet changes One mother disliked the odor of the medical food so much limit long periods of fasting, and minimize elevations of LEU A diet that reduces LEU intake is used to help prevent most based on your baby’s health, growth, LEU intakes, blood that she made a face every time she gave it to her son. metabolites. A high-carbohydrate, low-fat diet with LEU of the symptoms of a DLC. This diet, which is different for levels of LEU, and urinary excretion of organic acids. Because of this, he refused the medical food for several days restriction results in normal growth and development. A each person with a DLC, can lower the blood and urinary I-Valex®-1 Amino Acid-Modified Infant Formula with until she and her family realized what was wrong. As she said high carbohydrate intake with reduced fat intake is required organic acid levels to a range that may allow normal mental Iron is an infant formula used to provide protein for infants later, “We changed our attitude to thinking this wonderful to prevent the build-up of metabolites arising from the development and growth. and toddlers. I-Valex-1 does not contain any LEU. Similac diet will make it possible for our child to have a happy life.” breakdown of stored body fat (fatty acid oxidation). Carnitine Advance Infant Formula with Iron, breast milk, or other helps the body get rid of toxic metabolites that build up in the The special diet for your child is designed for his individual intact protein must also be fed to provide the specific amount Other children in the family should be told that I-Valex is body as well as help to prevent possible deficiencies. needs, and following it is very important. With proper of LEU your baby needs for growth and development. Breast very important, and they should not emphasize the difference nutritional management, your child will grow and develop milk is lower in LEU than infant formula or cow’s milk and in taste or odor between milk and medical food to the child 3-Methylglutaconic Aciduria Type I (meth-ill-glue-ta-con- normally. with a DLC. ic a-cid-ur-ee-a) is a deficiency of methylglutaconyl-CoA can be used to supply the required LEU. The decision to hydratase (meth-ill-glue-ta-con-ill Co-A hi-dra-tase) that Many foods contain protein. Those foods also contain LEU. breastfeed should be discussed with your nutritionist and Most children taking medical foods for a DLC like them IF results from an increased amount of 3-methylglutaconic acid Your child with a DLC must limit the amount of foods that metabolic doctor. The nutritionist or metabolic doctor will the medical foods are started early and IF their family has a released and blocks the body’s ability to break down LEU contain protein. Table 1 is a general guide of foods that are not tell you the exact amount of breast milk needed in addition positive attitude. Older children who start on the diet after (Figure 2). Symptoms range from isolated speech retardation allowed, foods that are limited, and foods that may be eaten to your child’s infant formula. I-Valex-1 contains carnitine drinking cow’s milk may not like I-Valex at first, but in time to slowing down of thought and a reduction in physical freely if obesity is not a problem. and is well supplied with fat, carbohydrate, minerals, and accept it. 6 7

Tips for preparing formula: formulas together. The I-Valex-1 mixture stored in bottles in 2 to 3 months of age. Before this time, the baby’s “tongue Table 2. Metric to English Conversions • Always follow the instructions on the label and mix the refrigerator may be warmed before feeding. thrust” causes the tongue to protrude, making swallowing Metric English formula according to the recipe provided by your • Shake the formula mixture and pour into a bottle. food difficult. Waiting to feed solid foods until the baby is nutritionist or metabolic doctor. developmentally ready is best. Solids • Set a bottle in a pan of cold water on the stove and I-Valex-1 is similar to infant formula, and the amounts, as 1 g (0.001 kg) = 0.035 oz • Wash your hands and all supplies carefully before preparing gradually warm it or run hot tap water over the bottle. well as the kinds of cereals, fruits, and vegetables prescribed 28 g = 1 oz formula. • Never use a microwave oven to warm formula as this can are about the same as would be fed any baby. Your baby’s 454 g = 1 lb • Mix in the approved natural protein if recommended by your result in hot spots that can burn your baby. nutritionist or metabolic doctor will advise you about when 1000 g (1 kg) = 2.2 lb nutritionist or metabolic doctor. • Always test the temperature of heated formula before your baby should start eating infant cereal and strained • Do not mix longer than indicated on the I-Valex label. feeding by shaking a few drops on your wrist. The formula baby foods, and which foods to introduce. Guidelines for Liquids • Overmixing causes the fat emulsion to break. Separation of should feel lukewarm. adding various foods to your baby’s diet are given in Figure 5. 5 mL = 1 tsp the formula mixture then occurs. Overmixing may also add • If the I-Valex-1 mixture drips freely, the nipple holes are However, your nutritionist or metabolic doctor may suggest 15 mL = 1 Tbsp air that destroys vitamins A and C. the correct size. Shake the bottle well before feeding. different ages. Follow their advice. 60 mL = 1/4 cup • Refrigerate the prepared formula after mixing. Discard any To feed your baby, sit in a comfortable place, hold her in the At about 7 to 8 months of age, your child may begin trying to 240 mL = 1 cup unused formula 24 hours after mixing because of nutrient loss. curve of your arm, and keep the nipple filled with the I-Valex-1 eat foods such as crackers, low-protein toast, or pieces of fruit 1000 mL (1 L) = 4 1/4 cup (1.06 qt) • Always test the temperature of heated formula before feeding mixture so that air will not be swallowed. You should burp without help. At about 9 months of age, your child may begin by shaking a few drops on your wrist. your baby at least once during and again at the end of each using a spoon. • Heating above 100° F (37.8° C) or adding hot water may cause feeding. Hold her upright against your shoulder or lay her face If your 9- to 12-month-old child has never eaten without help, Flavorings, such as Kool-Aid® Unsweetened Soft Drink down on your lap and gently pat her back. dip her fingers into the food to give her the idea of finger Mixes, Wyler’s® Unsweetened Soft Drink Mixes, and loss of vitamins A and C and lead to the Maillard reaction—a feeding. Later, you can teach her to pick up a spoon and help concentrated fruit juices can be added to I-Valex. I-Valex reaction in which some amino acids bind with carbohydrate, guide it to her mouth. Putting your child on your lap to guide may be made into a paste and combined with some allowed making them unavailable to the child. DO NOT WARM THE BOTTLE IN THE MICROWAVE. her hand may be easier. Start with thick foods such as mashed fruits, such as applesauce or other fruit purees, or combined Feeding Your Infant. The way you feed your baby with a Uneven warming may cause serious burns. potatoes since they do not slip off the spoon easily. with instant pudding mixes. Check the label, and be careful DLC is the same as for any baby. The I-Valex-1 formula will be which pudding mixes you buy, as some contain more protein supplemented with breast milk or infant formula such as Similac Introduction of Solid Foods. No baby is born with the ability Do not worry if your child does not eat all of the foods you than others. Advance EarlyShield. The nutritionist may have you mix the two to swallow solid foods. The swallowing reflex develops at measure out; just estimate what was not eaten, replace the INTERNATIONAL SYSTEM OF LEU with another food, and write it down. MEASUREMENT (METRIC SYSTEM) Age in Months The metric system is the International System of 1 2 3 4 5 6 7 8 9 10 11 12 Measurement. It is used for all medical and scientific measures. I-Valex-1 plus Similac Advance with Iron or breast milk In the metric system, solids are weighed in grams (g) or Strained cereals kilograms (kg) and liquids are measured in milliliters (mL) Strained fruits and vegetables or liters (L). A list of common conversions from the metric Very-low-protein foods system to the English system used in the United States is Cup feeding given in Table 2. The most accurate method to be sure your Self-feeding finger foods child is getting the proper amount of LEU is to weigh foods on a scale that reads in grams. Coarsely chopped foods Formula Preparation. Mix a 24-hour supply of formula at Self-feeding spoon one time or as instructed by your nutritionist. Feeding time should be a pleasant experience for you and your baby. Raw foods Figure 5. Suggested timetable for beginning solid foods and self-feeding. 8 9

When your child is older, the differences between the LEU- blood LEU and organic acid levels are well controlled. Various could harm your child’s growth and development, you will restricted diet and the diets of other children will be greater. methods are used to monitor the amino acids and organic acid be asked to take your child to the clinic frequently. If growth Your child with a DLC will require I-Valex all her life to levels in the blood and urine. Your baby’s metabolic doctor or and development are normal and laboratory concentrations provide most of her protein, mineral, and vitamin needs. nutritionist will determine how often your child is tested. remain within treatment range, the frequency of clinic visits Diet Guide and Food Lists. At each clinic visit, you will be Before taking a blood sample, you may be asked to accurately may be decreased with time. given guidance that spells out in detail what your child can eat. record your child’s total food and beverage intake. In this food At clinic visits, your child may be given developmental, The amount and how to prepare the medical food mixture, diary (notebook or form the clinic may provide), record the physical, and neurological tests. Family interaction, which is as well as the types and amounts of food that your child is name of the food, the exact amount in grams or household important to your child’s development, may also be evaluated. allowed, will be outlined. The nutritionist will help you work measures (cups, teaspoons, or tablespoons) that your child ate, Diet changes will be made, if needed, and any questions you out a plan that meets your child’s needs and fits into the family and the LEU content based on the food lists or information may have will be addressed. budget and lifestyle. given to you by the nutritionist. This will help the metabolic In addition to the metabolic specialist, you should have a local Lists of foods make meal planning easier and help you be sure doctor and nutritionist evaluate your child’s laboratory test pediatrician or family doctor to provide required ongoing your child’s nutrient needs are met. You will have time to results. well-child care. This doctor should give immunizations at become familiar with the food lists and their nutrient content, Urine Tests. A urine test may be requested by your metabolic the usual times, or you may obtain them from the health because foods will be added slowly to your child’s diet. doctor to monitor metabolic control. When a child is not department. When your child is older, you may need to use Free Foods getting enough calories, his body fat and protein may be used (see Table 1) to meet her energy needs. Free foods, which are for energy. In certain DLCs (ie, HMG-CoA lyase deficiency), YOUR CHILD’S GROWTH AND high in energy and contain little or no LEU, must not replace breakdown of body fat and protein may release ketones and DEVELOPMENT prescribed foods nor be used in large amounts. If your child organic acids, which can affect his health. Ketones may be By 4 to 6 months of age, your infant’s birth weight will double. eats too many of these free foods, she may become overweight, detected in the urine by the use of Ketostix®. Daily testing of The child with a DLC whose LEU intakes are well controlled or the extra sugar may cause tooth decay. Special low-protein the first urine in the morning will provide information useful and whose diet supplies adequate nutrients should grow as foods, including pasta, rice, crackers, cookies, and breads, can in managing your child’s diet. well as a child without a DLC. be added to the diet. These foods will help satisfy your child’s LEU and Organic Acid Levels. The amount of LEU in the During the second 6 months of life, the growth rate decreases. hunger. blood is an indirect measure of how much LEU is present in may be more pronounced in an open cup. Some parents find body tissues. Of most concern is the brain, because too much Your child may grow 1 inch (~2.5 centimeters [cm]) per month a training cup that has a lid and a spout to be very useful. If you are not able to find the LEU content of a certain food, LEU, organic acid, and ammonia, as well as too little sugar, during the first 6 months and 4 inches (~10 cm) total during Offering the I-Valex at a cold temperature may also increase ask your nutritionist. The nutritionist can calculate the are harmful to brain development. Because blood transports the second 6 months of life. This normal decline in the growth your child’s willingness to drink from a cup. nutrient composition of the food and help you include it in the nutrients to the brain, the concentration of LEU, organic acid, rate usually causes a decrease in appetite. diet plan if it is not too high in LEU. and sugar in the blood will give the doctor and nutritionist an During weaning, your child may not want to take all the idea of how much of these substances might be in the brain. Although the requirement for energy (calories) and protein prescribed I-Valex in liquid form. You may offer some of it in based on body weight decreases, the total daily requirement instant puddings, cereals, fruits, and soups, or it can be mixed Be sure to check with the nutritionist before Blood LEU levels that are high may indicate that your child is for most nutrients increases with age. You will need to adjust into a paste with fruits and fed by spoon. using any food that is not on the food lists provided. eating more foods that are high in LEU than his body needs food choices accordingly to ensure that your child has an for growth. Illness, such as colds and flu, can also cause the adequate nutrient intake. The nutritionist will help you with ADDITIONAL WATER MUST BE OFFERED WHEN body to break down its own protein, releasing LEU into the food selections that are right for your child. ® CHECKING YOUR CHILD’S PROGRESS blood. When your child is not getting enough protein, because I-VALEX IS FED AS A PASTE. of rapid growth or inadequate intake of the medical food, the Weaning from Bottle to Cup. When the time comes to Consult your child’s nutritionist. Laboratory Tests. Because your baby grows rapidly during blood LEU levels may also rise. Initially during rapid growth, switch from the bottle, your child may need extra attention, the first year of life, blood and urine samples will be tested the blood LEU level will decrease and then increase again as as any child would. Weaning takes patience, especially if your frequently to monitor how well her DLC is controlled, and the body breaks down its own protein. child shows no interest in drinking from a cup or a glass. A child of 15 to 18 months of age may drink more medical to indicate if changes in treatment are needed. Your doctor food from a cup if she is given a small pitcher of I-Valex and may ask for a blood and/or urine sample once or twice a week A low LEU level usually indicates that your child is not getting Begin offering I-Valex-1 from a cup when your child is is encouraged to pour it into a small cup without help. Many during your baby’s first 6 months, then once every 2 weeks enough LEU in the diet. between 5 and 8 months of age. Because taste buds vary on parents have found using brightly colored straws, special until 1 year of age. After 1 year of age, checking blood and urine different parts of the tongue, I-Valex may taste different when cups, or sports bottles to be good transitional tools to help levels and diet records may be decreased to once a month if Clinic Visits. Because a DLC is a lifelong condition that taken from a cup instead of a bottle. Also, the smell of I-Valex wean a child from the bottle. 10 11

Toddlers. Toddlers, children from 1 to 3 years of age, have a materials that you may find helpful are listed on page 15. Loss of Appetite. Loss of appetite can result from a variety also very important for both parents to support each other in slow growth rate compared with that of infants. Toddlers may Toddlers and Preschoolers. Permit your preschooler to make of causes including poor metabolic control; illness; eating too managing a food strike. If a child is allowed to eat foods not on gain 4 to 5 pounds (1.8–2.3 kilograms [kg]) a year, compared food choices, such as what fruit he wants to eat. Plan meals that many sweet foods or desserts that satisfy the appetite and her diet, LEU levels will not be controlled. with the infants’ gain of 12 to 22 pounds (5.5–10 kg) per year. have variety in color, texture, flavor, and preparation methods. decrease the desire to eat the foods prescribed; getting too On a food jag, a child wants to eat the same food or foods for Growth during this period involves changes in body form. Legs A child who is involved in food selection and preparation will much I-Valex, which may depress the appetite for other foods; long periods. If the foods are nutritious and are in the diet, lengthen and body fat decreases. Energy needs are decreased be more interested in trying a new food. Involve your child in or having a lower than normal blood LEU level. Medications there is no reason for concern. Remember that most of your because of the slower growth rate. However, mineral and planning menus to become familiar with foods allowed and may also decrease appetite. child’s nutrient needs are supplied by I-Valex. vitamin needs increase. excluded. Let him help grocery shop, set the table, and prepare Unusual Hunger. This may be an indication that the diet needs Toddlers seek independence and are very curious about the food. to be adjusted. The amount of I-Valex may need to be increased Inappropriate Feeding Behavior. Inappropriate feeding their environment. Because toddlers want to do things for because the table foods prescribed are not satisfying needs. behaviors, such as refusing to give up the bottle and/or At about 3 to 4 years of age, children want to serve themselves. Using low-protein foods is a great way to manage hunger difficulty in eating solids, chewing, or self-feeding, may result themselves, encourage your child to feed himself. Teach your child the proper food portions. One way to do this without increasing protein intake. from a variety of causes. These can include a delay in offering Preschoolers. Preschoolers also have a slow weight gain of is to use a “token” system. Tokens symbolizing 5, 15, or 30 mg table foods, delay in teaching the child to drink I-Valex by cup, 4 to 5 pounds (1.8–2.3 kg) per year. On the other hand, their of LEU, or 1 gram of protein, may be used to “purchase” foods Refusing Medical Food. A child may refuse I-Valex because of or not allowing the child to feed himself either with fingers total energy needs are greater than those of toddlers. Because containing these amounts. normal variations in appetite, and this should not be of concern or spoon. Always keep a positive attitude and make feeding a your preschooler’s nutrient and energy needs are greater, the School Age. When your child reaches school age, she will if average intake over a week is adequate. If I-Valex is not pleasurable event. nutritionist may tell you to increase foods with a high nutrient become more independent in many aspects of her life and offered regularly, a child may decide to refuse it. Improperly Try not to feed a child longer than necessary at mealtime to content. These foods are packed with vitamins and minerals eating is one of them. As she begins to develop logic and math mixed I-Valex also can cause refusal— too much water makes encourage self-feeding. Remember that small amounts of food and are energy dense. skills, it is important she use these skills to understand the diet. the volume too great; too little water makes the I-Valex mixture are usually wasted when a child first learns to self-feed, but Let your preschooler make some decisions. For example, Encourage your child to help prepare the medical food and too thick. A child may refuse I-Valex as an attention-getting this is normal. Keeping food records will help your nutritionist permit him to choose which cereal, fruit, or vegetable to eat. calculate the amount of LEU in foods. As your child gets older, device, especially if he senses that his parents are anxious for estimate your child’s intake. Be aware that most preschoolers want to do things at their she should understand what levels of LEU are considered him to drink the I-Valex mixture. Remember, I-Valex plays own speed. Be prepared to have your child spend so much time normal and the consequences of high LEU levels. an important role in providing most of your child’s nutrition A child may be using his diet as a way of getting attention or talking that little is eaten. This is normal behavior. needs. If refusal of the medical food continues to be a problem, manipulating parents. If your child has any of these problems, Adolescence. Adolescence may be a difficult time for both the use of a feeding tube may need to be considered. call the nutritionist. The nutritionist will give you support and Social Interaction at Mealtime. Mealtime is an important you and your child, regardless of the DLC! The influence of Refusing Solids. A child may experience normal variations in offer suggestions to help solve the problem. part of every child’s social development and, whenever friends and the struggle for independence may make dietary appetite or taste for certain foods. The prescribed amount of possible, the family should eat together. Younger children can compliance a challenge. Teens may feel that the DLC makes I-Valex may be too high and the energy in it is causing her to THE ROLE OF FAMILY AND OTHER CARE learn how to feed themselves by watching older brothers and them different from their friends. Eating out with friends is lose her appetite. PROVIDERS IN MANAGING A DLC sisters. part of growing up. Help your child develop the skills for eating Make meals for your child with a DLC as similar as possible to out, traveling, and “sticking” to the diet when not at home. Toddlers and preschoolers periodically have one of two Parents carry the bulk of the responsibility for managing the family’s meals. Menus for him can be planned from those Sometimes teenagers with a DLC would rather tell people they characteristic feeding behaviors that cause parents concern. their child’s DLC. If possible, try to share the responsibility for the rest of the family. For example, whenever possible, are vegetarian or vegan than explain about the DLC. Help your They may decide to stop eating by going on a “food strike,” or in preparing meals and monitoring your child’s diet. Other use the same fruits and vegetables for everyone. You can also teenager deal with her peers and not be self-conscious that she they may go on a “food jag.” Food jags and strikes are common children in the family, as well as the child with a DLC, prepare a low-protein pasta or meatless dish that is similar to has a DLC. Finding a peer with a DLC through support groups among young children. should learn about the diet as soon as they are old enough to the one served to other family members. The family’s help and can be a great comfort for a teen. Ask the clinic for resources understand it. Older brothers and sisters should be encouraged support are very important to maintaining the diet. and suggestions. During a food strike when your child refuses to eat, offer food to be involved in feeding the child with the DLC so they at usual mealtimes, and if she refuses the food, take it away. become familiar with foods allowed and excluded. Make sure TEACHING YOUR CHILD DIET FEEDING PROBLEMS Allow only water between meals. She will become hungry and they understand the importance of the diet for their brother’s MANAGEMENT Parents may be tempted to treat their child as a “sick” child then eat. Remember that I-Valex supplies most of your or sister’s health. Brothers and sisters should not feel sorry for and not follow their usual patterns of child rearing. The child child’s nutrient needs, so her medical food should never be the child with the DLC because he is on a special diet. Treat Explaining the diet can begin by calling allowed foods “special” restricted. your child with a DLC as normally as possible. or “just for you.” From the time your child is very young, with a DLC is a normal child who needs to manage food intake teach her to ask about unfamiliar foods before eating them. As carefully. Ask your child’s doctor, nutritionist, public health Do not give in to a food strike and offer Free Foods or foods Grandparents love to spoil their grandchildren! It may be your child grows older and is able to understand the concept nurse, or social worker for support and help if any of the that are not on the LEU-restricted diet. The nutritionist can difficult for them as they sometimes feel the child with the of a missing or nonworking enzyme, explain the DLC. Some following problems should occur. help you during this trying time, so do not hesitate to call. It is DLC is “missing out.” It is important they understand the 12 13

diet and become actively involved as much as possible. A grandmother may be the ideal person to experiment with low- Mother’s Genes Father’s Genes Mother’s Genes Father’s Genes protein cooking and provide special low-protein treats. Explain the DLC to relatives, friends, day-care providers, baby- sitters, and all teachers. They should become familiar with foods allowed and excluded, and understand the importance A B Normal Gene A B Normal Gene of the diet. Give a list of the foods allowed and not allowed to DLC Gene DLC Gene anyone who feeds your child and explain the list as well as the exact menu. C D C D Tell everyone who cares for your child that even “just a little bite” of a high-protein food is not allowed. Emphasize what can happen if your child does not stay on the diet. Figure 6. All children of a person with a DLC and a person who does Figure 7. Approximately half of the children of a parent with a DLC Here are some suggestions of things to do when your child is ill not have a DLC will be carriers of a DLC. and a parent who is a carrier of a DLC will have a DLC. YOUR CHILD’S DIET DURING ILLNESS with fever. A body temperature greater than 98.6° F (37° C) or a rectal • Do not force-feed food or I-Valex, especially if your child is A LOOK TO THE FUTURE their metabolic doctor and genetic counselor before another temperature over 100° F (37.8° C) is a fever. During fever, the nauseated or vomiting. Soda crackers may be the only food pregnancy. body’s rate of using food for energy speeds up. If extra energy he will feel like eating. Encourage intake of any allowed Continuing the Diet. A DLC is a serious health concern. is not supplied during illness, the body will break down its foods that your child is willing to eat. Treating a child as early in life as possible may prevent If you decide to have another child, give yourselves time to own muscle protein and fat stores for energy. Muscle protein • Encourage your child to continue drinking his medical food developmental delay and severe neurological damage. Not adjust to providing for the special needs of the first child. breakdown (and fat breakdown in some DLCs) needs to be if he tolerates it. following the LEU restricted diet may cause mental and Parents will want to be skilled in diet management for the DLC prevented in children with a DLC because it will release too • Offer Pedialyte® Oral Electrolyte Solution with added neurological damage at any age. Lifelong nutrition support before having another child. much LEU and organic acids into the blood. LEU and organic carbohydrate, such as dextrose or table sugar (3 Tbsp sugar must be adapted to each person’s needs. Metabolic doctors and acids are carried to the brain and other body organs where they to 8 fl oz of Pedialyte); Pro-Phree®; non-cola carbonated nutritionists provide support that is essential for helping your Offspring of a Person with a DLC. All children born to a may have a harmful effect. Give your child extra low-protein beverages; sugar sweetened carbonated beverages; Kool- child have a normal, productive life. person with a DLC will be carriers of the gene or have a DLC. food, formula, and fluids during illness. The extra food will Aid®; Tang®; tea with sugar; vegetable broth; or fruit juices As shown in Figure 6, all offspring of a parent with a DLC ( decrease the amount of muscle protein broken down for body with some sugar added. Family Planning. The chance that two carriers of a DLC will ) and a parent who is normal( ) inherit one normal ( energy. • Dilute the I-Valex mixture, or use liquid Jell-O® if it is have a child with a DLC is 1 in 4, or 25%, for each pregnancy ) and one DLC ( ) gene. Each one of their children will be a tolerated. (Figure 4). Because you have a child with a DLC, you know carrier. If a person with a DLC has children with a carrier for Feeding an ill child can be very difficult. Often a child with • Freeze any of the beverages listed and make into chipped that both parents are carriers. That means you have a 25% risk DLC, approximately one half (50%) of their offspring will have fever is restless and has a loss of appetite. The illness might ice. Frequently feed small amounts of this chipped ice to with each pregnancy of having another child with a DLC. The a DLC and one-half (50%) will be carriers (Figure 7). also include stomach upset, nausea, or vomiting. A child may provide energy and prevent dehydration. chance that two carriers will have a child who is a carrier is 1 become very dehydrated because of the high body temperature • As your child’s appetite improves, gradually return to the of 2, or 50% for each pregnancy. Childbearing by Women with a DLC. For the woman with and a lack of adequate fluid intake. usual diet plan. a DLC, having children may cause problems. A major concern Before a couple with a child who has a DLC plan to have any for the DLC women is the stress of the pregnancy on her If you suspect a cold or virus, or if your child has a fever, it Emergency Letter. Individuals with DLC should have an more children, they should take time to seriously think about metabolic control. The nutritional requirements can rapidly is important to call your pediatrician or metabolic doctor emergency letter with them at all times. This letter provides the special parenting tasks that parents of a child with a DLC change during the course of a pregnancy. Pregnant women immediately. Illness in a child with a DLC can be very serious. important information such as the name of the condition, must manage. Genetic counseling is recommended to review must be monitored carefully for their own safety, as well as the Your metabolic doctor or nutritionist will help you decide on explanation of symptoms, the importance of timely treatment the risks, and to discuss several reproductive options that are health of their baby. how to manage it. and treatment strategies, and your metabolic doctor’s contact available before and during pregnancy. information. In times of illness or stress that may require DLCs are a serious health concern. However, by following Ask your nutritionist for a “sick-day plan” to use during illness. hospitalization, this letter can be presented. This letter can be While there is no test that can determine if another child will an LEU-restricted diet closely and keeping blood LEU levels A sick-day plan provides adequate calories to meet energy needs provided by your metabolic team. be affected with a DLC before a pregnancy, prenatal testing within the treatment range, the person with a DLC can lead and helps keep your child out of the hospital. Ask about using may be possible during the early part of the pregnancy. A a normal, productive life. Successful pregnancies require medication such as acetaminophen (Tylenol®) to reduce fever. couple may want to discuss and consider all their options with attentive diet monitoring during the prenatal, labor, delivery, and postpartum periods. 14 15

RECIPES RESOURCES ® ® ® Kool-Aid -Flavored I-Valex -1 Fruit Juice-Flavored I-Valex -2 Support Groups/Newsletters Ener-G® Foods, Inc. Yield: 8 fl oz Yield: 8 fl oz Organic Acidemia Association 5960 First Avenue South 40 g I-Vales-1 20 g I-Valex-2 9040 Duluth St. Seattle, WA 98108 3 Tbsp, level, sugar1 3 fl oz concentrated apple, grape, or orange juice Golden Valley, MN 55427 Phone: (800) 331-5222; (206) 767-3928 1/4 tsp Kool-Aid or Wyler’s® Unsweetened Soft Drink Mix Water (room temperature) to make 8 fl oz Phone: (763) 559-1797 (Central Time) Fax: (206) 764-3398 Add water (room temperature) to ingredients to make Warm juice concentrate to room temperature. Place all Fax: (866) 539-4060 (Toll Free) Email: [email protected] 8 fl oz. Mix in a blender at lowest speed no more than 4 ingredients in a blender at lowest speed no more than 4 Email: [email protected] Website: ener-g.com seconds. Or, shake briskly in a closed container for 10 to seconds. Or, shake briskly in a closed container for 10 Website: oaanews.org Med-Diet® Laboratories, Inc. 12 seconds. Serve chilled. to 12 seconds. Serve chilled. 3600 Holly Lane, Suite 80 Nutrient 1 fl oz 8 fl oz Nutrient Apple Grape Orange Low-Protein Food Suppliers Plymouth, MN 55447 Lysine, mg 0 0 juice juice juice Canbrands Specialty Foods, Inc. Phone: (800) 633-3438 (MED-DIET); Protein, g 0.75 6 Lysine, mg 33 15 48 3500 Laird Rd. Unit 4 (763) 550-2020 Energy, kcal 42 336 Protein, g 6.5 6.7 8.6 Mississauga, ON, Canada L5L 5Y4 Fax: (763) 550-2022 Energy, kcal 257 275 252 Phone: (905) 829-6003 Email: [email protected] 1 Email: [email protected] Website: med-diet.com Osmolality (concentration of particles in solution) may be too high if more sugar is added, which may cause bloating and diarrhea. Website: canbrands.ca 2 The amount of drink mix may be varied according to taste preference. *Please check with your dietitian or doctor before using this recipe in infants. PKU Perspectives Dietary Specialties Lindon, UT 84042 8 S. Commons Rd. Phone/Text/Fax: (866) 758-3663 Waterbury, CT 06704 Email: [email protected] ® ® Additional Tips for Flavoring I-Valex Phone: (888) 640-2800 Website: pkuperspectives.com Kool-Aid -Flavored I-Valex -2 Website: dietspec.com Yield: 16 fl oz Medical Food Taste Connections, LLC 40 g I-Valex-2 • Add chocolate or strawberry syrup. Phone: (310) 413-6499 3 Tbsp, level, sugar1 • Mix I-Valex with fruit to make a “smoothie.” Fax: (310) 318-8407 1/2 tsp Kool-Aid or Wyler’s Unsweetened Soft Drink Mix2 • Freeze flavored medical food into “slushies” or Email: [email protected] Add water (room temperature) to ingredients to make 16 fl “popsicles.” Website: tasteconnections.com oz. Mix in a blender at lowest speed no more than 4 seconds. • Add dry I-Valex to pudding (lemon, tapioca, Or, shake briskly in a closed container for 10 to 12 seconds. vanilla, etc) mixture. Prepare pudding with non- Serve chilled. dairy creamer. Nutrient 16 fl oz Use low-protein food lists to calculate LEU content Lysine, mg 0 of flavorings. Protein, g 12 Energy, kcal 308 1 Osmolality (concentration of particles in solution) may be too high if more sugar is added, which may cause bloating and diarrhea. 2 The amount of drink mix may be varied according to taste preference. Jell-O, Kool-Aid, Popsicles, Tang, Tylenol, Kuvan, NutraSweet, and Wyler’s are not registered trademarks of Abbott Laboratories. 17 16

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 Call To Get Started: 1-855-217-0698 (M-F, 8:30 a.m. to 5:00 p.m. EST) Tyrosinemia Isovaleric Acidemia and Homocystinuria 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 ® I-Valex 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 20205033/January 2023 LITHO IN USA