SHARING

One of the most efficient ways to share with others about MSUD is through the use of e-mail. A year and one half ago Emily, an adult with MSUD, set up a group e-mail account hosted free by yahoogroups.com. This MSUD eGroup has grown to about 40 families and adults with MSUD. Each member receives every e-mail sent to the group. In this section, members share what the eGroup means to them.

The article “Misdiagnosed” reports one of the most amazing results from sharing with the eGroup. Beth Mauldin from Florida joined the eGroup in March 2001. Her son would probably still be limiting his protein intake if she had not sought help from other families.

you may question why Ben Mauldin’s urine smelled of maple syrup, but he did not have MSUD. The Support Group hears from many parents concerned about this odor on their children. Occasionally we hear from an adult and even some who say their animal has the maple syrup odor! This sweet smell is evidently rather common, more often in perspiration than in urine. Only those with MSUD are known to have the maple syrup odor in both their urine and ear wax.

Misdiagnosed with MSUD

In December 1999, when our son Benjamin was seven months old, he ate his first substantial protein load. Being fish-egg-dairy vegetarians, we gave him salmon. He loved it and ate a portion we later calculated to be about twenty grams of protein. About two in the morning, he became very agitated, made a high- pitched repetitive cry, stared vacantly, and was inconsolable and unresponsive. My husband and I almost took him to the hospital before he settled down, became responsive, and went back to sleep. In the morning, we found a dried urine spot on his pajamas that smelled oddly like maple syrup. I first suspected that he might be diabetic, but on a whim I checked the Merck Manual's index for maple syrup. Much to my astonishment, I found a listing for maple syrup urine disease and read about how effected persons have an inability to metabolize particular amino acids. Believing there could be a connection between our terrible night and Ben's salmon dinner, I consulted the Internet for more information and then made an appointment to see our pediatrician.

After scouring through the old newsletters and general information on the MSUD Family Support Group web site, I had many questions for our doctor. She told me that it was impossible for Ben to have a metabolic disorder and look so well. According to the information I found on the web site, that was not necessarily true. My impression was that if substantive damage had not occurred, a child could appear, and actually be, well.

Once again, I turned to the web site. This time I found Dr. Susan Winter's e-mail address. I sent her a question regarding variant forms of MSUD and asked whether my son should be tested. Dr. Winter responded very quickly. Yes, he should be tested, and a plasma quantitative amino acids test would be the starting point. After a bit of arm-bending, our pediatrician ordered a test which came back mildly abnormal. (The test was inferior to the one recommended by Dr. Winter.) Dr. Winter believed the degree of elevation was inconclusive and suggested that we look for alloisoleucine.

The labs in the area had no information on how to find this marker and could not perform the test. We were then referred to the head of the pediatric metabolic and genetics department at a regional teaching hospital.

After months of waiting, in April 2000, when Ben was 11 months old, we saw the specialist and another quantitative amino acid test was ordered with a protein load.

It too came back abnormal with two times normal valine and leucine, and three times normal isoleucine. Several other amino acids were also elevated. At the bottom of the test report was an interesting notation. “In this sample, the concentrations of several unrelated amino acids were elevated. This pattern is non-specific and likely represents a dietary artifact (non-fasting sample).”

Ben was then given high doses of thiamine and another test was performed with a protein load. Similar elevations showed up along with the same notation. To me this notation suggested that the results showed that my son had eaten before the test and potentially nothing more.

After consulting with our specialist, I asked about this notation and the other elevated amino acids and my question was circumnavigated. I also asked about looking for alloisoleucine and was told this was not necessary. We were told that Ben's pattern of elevation was typical of the disorder and that no further tests were needed. I asked if there could be a problem with his liver, and the answer was no. His ears were not swabbed for the distinctive maple syrup odor. With only the results from one type of test, Ben was diagnosed as having a mild variant form of MSUD. He was placed on a two gram of protein per kilogram of body weight diet and ordered to return in a year.

I went home wondering to myself how the two gram diet was determined? How did the specialist know my son’s liver was functioning properly, and how could you rely on tests that were conducted with arbitrary protein loads? Why were other amino acids elevated, and why were different ones elevated on a repeat of the same test? Did the notation really mean that Ben's amino acids were elevated simply from the food he ate?

After months of these questions nagging at me and having a specialist who was, for whatever reason, incapable of providing answers, I joined the MSUD eGroup. I was overwhelmed by the seriousness of the disorder and the degree of monitoring that was supposed to be done. I had never heard of DNPH testing. Ben was not on formula. We had no sick day plan. We had no substantive dietary counseling. Other eGroup children’s blood leucine levels were monitored monthly, weekly, and even daily in some circumstances. It was clear that we were not getting quality care.

Then the breaking point came—our son started vomiting in the evening. This happened several times over a two week period and was a red flag to other MSUD parents that Ben's leucine levels were elevated. Another eGroup parent actually phoned us believing that our son’s situation was potentially quite serious.

We knew we needed to see a doctor who was knowledgeable about MSUD, and, unfortunately, we were already seeing the most qualified doctor in our area. We called Dr. Holmes Morton. Even though he typically does not work with variants, Dr. Morton consulted with us over the phone. After listening to the little information I had and hearing the fact that our son's ear wax never had the maple syrup smell, Dr. Morton suggested we come to Pennsylvania so that he could rule out MSUD as our son’s problem.

I was stunned with the suggestion that Ben may not have the disorder that had nearly consumed me with worry for over a year. Dr. Morton suspected that Ben's problems—vomiting, irritability, restlessness, insomnia, hyperactivity, head-sensitivity, head-banging, and thin hair—stemmed from causes other than MSUD. Needless to say, we were off to Lancaster.

When we arrived at the Lancaster General Hospital, our room was waiting for us; Dr. Morton arrived shortly thereafter. We stayed overnight and several tests were performed. One test showed that Ben metabolized valine and phenylalanine (the control) at similar rates which meant that he had no trouble with valine. Next, Ben ingested several doses of leucine over several hours. His blood was checked, and there was no accumulation, which meant his body also metabolized leucine. His liver was checked, and its function was normal. We were stunned and thrilled. The conclusion: Benjamin never had any form of MSUD.

How had this misdiagnosis happened? We believe there were two primary explanations. The first was likely caused by the sheer broadness of the fields of metabolics/genetics. Many doctors may have little experience in diagnosing and treating one of the many rare disorders that fall into this category, unless of course, that particular disease is their speciality. In hindsight, we know that we should have asked our specialist how many patients with MSUD he had diagnosed and treated.

Our second explanation for the misdiagnosis is that we were not sufficiently forceful or persistent in getting clear explanations for our questions. The moment I was given a vague answer, and when it was apparent that further questions were not welcome, we should have immediately sought another doctor. Ultimately, we learned that the care and welfare of our children is a parental responsibility and parents must be their child's advocate. Never stop asking questions and make sure that you are getting substantive answers. Thankfully, we also learned that there are amazingly competent, patient doctors who are willing to help and provide complete information.

Dr. Morton and his colleague, Dr. Strauss, believe that there is a possibility that Ben has been experiencing pediatric migraines which could explain his many symptoms. He is currently under observation, and when he has greater verbal ability this diagnosis could be confirmed.

We would like to thank Dr. Susan Winter, who was instrumental in having our son tested quickly. It would likely have saved him from neurological damage if he actually had MSUD. We would also like to extend our deepest thanks to Dr. Holmes Morton, who, as many of you know, is not only a brilliant doctor but also a most generous and wonderful man.

—Beth Mauldin

We, on the eGroup were all concerned: Did Ben suffer any damage from being on the restricted protein diet for 15 months? In an e-mail after their visit with Dr. Morton, Beth wrote that the doctors did not think there was any permanent damage. The two gram per kilogram diet probably would have been too high had Ben had a variant form of MSUD. He was still getting infant formula, cheese, soybeans and peanut butter—basically a vegetarian diet. He is at the top of the growth charts, and has met all the milestones for his age.

Since Beth wrote this article in Oct. 2001, she and her husband think they have discovered the cause of Ben’s vomiting episodes. They believe feeding him milk along with acidic fruit causes curdling in his stomach and subsequent vomiting. Eliminating the combination has eliminated the vomiting. Ben is still a very intense boy and does not have a good appetite. But who can figure out all the behaviors of any almost three year old! Now they at least know it is not related to MSUD.

With No Prior Experience

With the birth of my second grandson in 1998, I was introduced to MSUD. As the day care provider for my grandsons, one with MSUD and the other with Pervasive Development Disorder (PDD), I learned firsthand the special challenges for both. Internet support groups and eGroups were my outside source of information. Messages on these groups soon made me realize the laws in Missouri were more limiting for MSUD than for PDD.

A chance meeting with our State Representative gave me insight into the possibility of changing these laws. With no prior experience, but with advice from the eGroups, I commenced a journey though the Missouri General Assembly. Through the eGroups I contacted as many persons in our state as possible. I prepared an instruction packet with pre-written letters for these persons to send to their legislators. These packets were distributed to others in the state through clinics.

Families were extremely helpful and very willing to unite. By the second year, a bill was passed that will require the insurance industry to cover low protein foods for Inherited Disorders of Amino Acids. The new law fell short of our original goal (it has a $5000 a year cap, with coverage for those up to six years of age), but it is a large step in the right direction. The support groups and eGroups will continue to be used as we pursue our goal. We united for a common goal, and for this I am thankful.

—Marcia Hubbard

Comments from eGroup Members

Celeste Battle, California

The MSUD Newsletter, the web site and the eGroup are life-savers for the family with a child having this genetic disorder. My son Brock is 23 years old with Classic MSUD. We spent many years feeling very isolated, as if we were the only family dealing with MSUD. Then we were told about the MSUD Newsletter by a physician at Buffalo Children’s Hospital. Life got easier knowing there were others just like us! Sharing and learning helped us survive. Now we have the web site and the MSUD eGroup to help us.

I have learned so much from communicating with others about this disorder. After all these years, I am still learning about MSUD, the effects of certain medications on the amino acid levels, gaining new ideas on managing illnesses and mood swings, etc. This group is a lifeline, a sounding board, a question and answer board filled with outstanding, objective information and true life experiences which are the best learning tools. My heartfelt thanks go to all who contribute information. I for one would not want to be without this eGroup and the Newsletter. They make difficult times so much easier to handle! Thanks to all of you.

Sandy Kiel, Michigan

I enjoy the eGroup because I face so many problems and ideas every day. It's like having your neighbor over for coffee to discuss your kids; only our neighbors are across the world, and our kids have very unique problems. We all share the same goal—healthy children—and want to help each other reach that goal. It's a big comfort to know there are many others struggling with the same issues I struggle with every day: formula, nutrition, food likes and dislikes, and hospitalizations. We are able to draw on each others’ experiences, which is invaluable. The group is more than an exchange of information. It is support and encouragement for each other.

Nikolai Rudd, Massachusetts

What I have found to be most interesting in being part of the eGroup is the information on problems people are having, especially the older group of persons with MSUD. We seem to be having problems we had not encountered when in our teens. From those participating in this group, I've learned that we older ones experience similar symptoms. So, when I had appointments with my doctors, I was able to give them information about others who were experiencing the same problems.

As an adult, I feel we are the guinea pigs of this disease. No one really knows if other problems will arise in the future because of something lacking in our diets. It is encouraging when I read about the plight of other people and together we try to figure out what may be happening. In a sense, we are like the characters on "Dark Angel."

We are encouraged to believe that our diets are doing what they are intended to do, but are they? We need to share experiences with each other more frequently than every two years at the Symposiums. Changes are happening during those two years. Are others also finding they are becoming ill more easily? Are they having chronic back pains and other chronic problems?

I find it both encouraging and somewhat alarming that a lot of the older MSUD persons are experiencing symptoms of "anxiety disorder" as I have experienced. This is an issue that we should not take lightly, even though it is a common disorder, and may not pertain to MSUD at all. As a group, we need to examine the possible connection to MSUD so the next generation of adults will be able to prevent this problem and others.

Calling everyone to discuss problems costs more money than I can afford. So I am thankful for this group which allows each of us to freely express ourselves and even help others. My only regret is that there are not more teens/adults using the eGroup as a resource. But if any one has questions that they'd like to ask about school, sports, fitting in, etc., I'll be more than happy to help answer them as I'm sure the other adults would too. Feel free to use us as resources at the Symposium. Chances are, I'll use you too.

Monica Falconer, Alaska

After our first son was diagnosed with MSUD—a condition we had never heard of before—we felt alone, scared and insecure. But this feeling only lasted a few weeks. Soon after we came home from the hospital with our recovered son, we sat down at our computer and looked for the MSUD Support Group we had been told about at the hospital.

We wrote an introductory message to the MSUD eGroup, and, to our surprise, half an hour later we received at least four messages from families welcoming us and letting us know that they were there— somewhere in the country, maybe living far from us, but always only a computer screen away. It was an amazing feeling of support right away.

I remember that when we received those messages we felt good for the first time since we were told of our son's diagnosis. Now we know that we have families, friends, persons who are there for us with information, or to help us find the answers to all our questions, to give us the support that we all need.

We had never been told about the DNPH solution as a way to check for elevated levels of leucine. It was through the eGroup that we first heard of it. Despite our doctor's reluctance, we were determined to give it a try. We no longer have to be "in the dark" when our son's behavior changes, but can use DNPH to see if it has something to do with his elevated amino acid levels.

The MSUD group is like a second family to us. A family that we keep in contact with very frequently, a family that we think of daily, and a family that we love, appreciate and are very proud of. For families with relatives with MSUD, we highly recommend that they join the eGroup. It's just great!

Denise Pinskey, Michigan

I love having the MSUD eGroup. It's great to ask other MSUD families questions and get a quick response. Sometimes it is very hard to explain the disease to our family and friends and get genuine understanding. When I have a question, I know everyone in the eGroup will give an honest opinion from the MSUD perspective.

Patty Swenson, Colorado

I have found the MSUD group e-mail very valuable. Even though we have been living with Classic MSUD for 31 years, there is still so much to learn. We were able to start using isoleucine and valine supplements last year as well as DNPH for the first time. So even though I am an "old-time MSUD Mom," I was new with supplements and DNPH. All of the MSUD parents in the group helped me to completely understand and use the newer tools to manage MSUD. It has been very supportive to have other parents helping when you have no one else to talk to about MSUD. I find the eGroup helpful and supportive. Thanks!

Melisa Carr, South Carolina

The MSUD eGroup has been a very big help to me in learning about MSUD. Through questions and comments made in the e-mails, I found out several things that have improved the quality of life for my child Karena who is now 17.

Karena was diagnosed with variant MSUD at the age of 15. The doctors told me it was something they reviewed in medical school, but they were told never to expect to see anyone with the disease. I went to the Internet in search of information regarding her diagnosis. I was led to the MSUD web site and have been reading ever since.

Karena was in a psychiatric hospital for severe auditory, visual and tactile hallucinations. I was told that I should put her in an institution, that I would never be able to take care of her. She was on multiple psychotropic medications. She was not able to take care of herself; she drooled constantly from side effects of the medications. She had severe tremors of her hands and stared into space most of the time unable to comprehend what was going on around her. She had an MRI done at that time to check for possible causes of her mental and physical deterioration. The MRI showed changes in the white matter of her brain. This led the doctors to do a spinal tap. The diagnosis of MSUD was revealed in the tests run on her spinal fluid.

Karena was started on the protein restricted diet and an MSUD formula. This was an extreme adjustment for her; she was no longer able to eat whatever she wanted. She hated the formula. That was a battle I dreaded three times a day, every day. She would gag and vomit as she tried to drink it. We tried every product available. She now takes the amino acid complex blend mixed in apple juice twice a day.

I had, at one point, asked the eGroup if any other children had hallucinations. Many responded that there were times when their children's levels were high that they talked about seeing objects that were not there. With this information, I began to keep a close watch on Karena's levels to see if they correlated with her hallucinations. I noticed that she only experienced hallucinations when she was sick or her levels were high.

In March, after several months of monitoring, I talked with her doctor about my observations along with the information I had gotten from the eGroup. I asked that we try taking Karena off her anti-psychotic medication. She was weaned over a four-week period.

A week after she was completely off the medication, her tremors were gone, although she was still groggy most of the time and not able to stay on task. Not too long ago, I learned through the group that valproic acid should never be given to people with MSUD. Karena was on a large dose of Depakote SR, an extended release form of valproic acid. She was always lethargic and extremely irritable. At times she would not eat well, and her levels were always low. I informed her doctor about what I had learned through the eGroup, and she agreed to try Karena off the medication. This was about six weeks ago.

Since that time, Karena is much more alert. She is able to stay on task, complete her school assignments, and is going to start attending regular classes this fall. She has been on homebound schooling for the past three years and was making no progress. The teachers had labeled her as non-educatable. They were suggesting that we give up and allow her to complete high school this year with a certificate of attendance. Now she is eligible to start working towards her diploma again, although she will start slow. It will be four more years before she will have enough credits to graduate.

I share the valuable information I obtain from the eGroup with Karena's doctors and dietician. I feel that personal experience and sharing are the best tools for learning. There is a lot to learn from one another. I am grateful to all of the participating members for sharing their knowledge and experience, and I enjoy reading the e-mails I receive.

I hope that some day I can share the type of valuable information that I have gotten from this group and make as big a difference in someone’s life as they have made in ours. Thank you.

This eGroup has been very active this past year and covered many subjects. Parents ask: How do you get a child to drink the formula when they refuse? Do other children with MSUD have problems when it is hot? How do others mix their formula so it is well blended? What new low protein foods are well liked? How have others reacted to anesthesia? Many other topics have been covered and each person learns from the responses.

You can be part of this exclusive group e-mail account. Contact Emily at this e-mail address: emilytalley@mindspring.com. Ask to be added to the MSUD eGroup and be sure to tell her how you are connected to MSUD—as a parent, teen or adult with MSUD or a professional dealing with MSUD.

Our Experience with Valproic Acid

Lisa A. O’Brien (Machak)

My daughter Mackenzie Erin—we call her M.E. for short—was born December 30, 1997. She was diagnosed with classic MSUD at 15 days, one day after being admitted to the hospital. Her metabolic doctor estimates that her leucine level at diagnosis was about 4000 µmol/l or 52.5 mg/dl. Peritoneal dialysis brought her out of her semi-comatose state. Her MSUD was under control at approximately 2 months of age, when I noticed that her eyes would flutter and roll back at times and on occasion her arms and legs would jerk randomly. We were referred to a pediatric neurologist who diagnosed a severe disorder caused by damage from the late diagnosis of MSUD.

She was started on phenobarbital and monitored with EEG’s repeated every 3 to 6 months. Each one proved to be normal. Finally, after 1½ years of phenobarbital, her EEG’s showed no more seizure activity, but were still abnormal. The neurologist told me that M.E.’s logic, reasoning and speech area of the brain were affected. The abnormal EEG’s were just her. M.E. was weaned from the phenobarbital and went on to meet her developmental milestones pretty well with some slight delay.

M.E. remained seizure free with no medication until in February 2002. She and I were cuddling on the bed after her bath and she seemed warm. I felt her head and took her temperature. It was 102.5°. I had just laid back down with her when her eyes rolled back, and she started having a grand mal seizure. It was the most frightening thing I have ever seen other than when she almost died before being diagnosed.

She was admitted to the University of Illinois Hospital at Chicago. All her pediatric specialists are there. She was started on valproic acid because she was having seizures approximately every hour even without a fever. The neurologist dismissed the possibility of febrile seizures and her 12-hour EEG showed severe seizure activity. I need to point out that her leucine level was a beautiful 150 µmol/l (2 mg/dl) at this time.

After a week in the hospital, with valproic acid levels at a therapeutic level, we returned home. Another battle fought and won—or so I assumed.

Within 5 to 7 days, I noticed M.E.’s behavior began to deteriorate, worse than it had been. (We believe she has ADHD and will soon have a diagnosis). She became extremely irrational, acting bizarre and very aggressive. Her leucine began to climb for no apparent reason. She wasn’t sick or off-diet. I made a few phone calls to her metabolic doctor and neurologist and asked, “Could this be the valproic acid causing these behaviors and the high leucine level?” (Deep down inside, a mother knows the answer to these questions and more—it’s getting the doctors to listen.)

I continued to raise the question for the next three weeks while M.E. was given nothing but apples and applesauce. Her leucine continued to rise higher and higher. Her irrational behaviors became fewer and farther apart as she grew lethargic, became ataxic and started hallucinating. M.E. is fed via G-tube, so she continued to receive her formula as usual. She had been on valproic acid for 1½ months.

She was semi-comatose when admitted with a level of 1800 µmol/l (23.6 mg/dl). Now mind you, M.E. has been hospitalized so much in her four years of life, we are a household name there. But this time was different. They did CAT scans and Mannitol was on order, but not needed. MRI’s were needed but couldn’t be done—too risky they said. I had gone this road with her alone since birth and had been so strong. This time I was as limp and helpless as she was while lying there.

As I searched the depths of my soul for strength, a very kind resident doctor came into the room. He said, “Mom, it says here that you believe that valproic acid is causing this metabolic crisis.” I jumped up and said emphatically, “Yes, I do!” Then he stated, “But there is no data to back this up.” At this point, I told him to call the neurologist and tell her I wanted the valproic acid stopped immediately!”

This very kind resident doctor then ventured on a tireless search to come up with some type of data to prove this. I had hope and strength again. Within 12 hours of our discussion, he produced an abstract describing the interaction between valproate and branched-chain amino acid metabolism. (See a reprint of the abstract in the box below.) The valproic acid was discontinued. Later, in a humorous moment, he and I joked about who would get the credit—I gave it to him. He gave it to me, stating that I knew all along but didn’t know where to find proof to back up what I thought.

Within 24 hours of stopping the valproic acid, M.E.’s levels started to drop, and she became a little more alert. Each day in ICU there would be an agonizing wait for leucine levels of the day. Finally, after 4 days, she was discharged with a level of 250 µmol/l (3.3 mg/dl). She was now on Phenobarbital Elixir instead of the valproic acid.

Since then, M.E.’s MSUD has remained under control, although we have run into problems with the Phenobarbital Elixir. M.E.’s behavior became very hyperactive, and she started with bizarre behaviors within a week or two of beginning the new medication. I phoned the neurologist. He said they have a lot of complaints about this medication. Apparently there is an ingredient in the Elixir that causes this (possibly a dye or alcohol). So we switched to the tablets approximately two weeks ago. I crush and dissolve them and put them through her G-tube.

I have noticed a small improvement in hyperactivity and behavior although not as much as I hoped. Much of what we are seeing could be the ADHD with the phenobarbital exaggerating the symptoms. I want to add that I was told by our neurologist that phenobarbital is usually not the anti-seizure drug of choice for children, because over time and continued use, it has been shown to lower the I.Q. by a few points.

As it stands right now, we will be doing another EEG to determine whether to continue medication or explore other choices. Our two other choices for anti-seizure drugs have severe side effects. As for M.E., she is forever smart, charming and inquisitive despite all her setbacks. She continues to amaze me each and every day. Bless her heart.

Be Aware of These Potential Problems

1. FOOD POISONING: It is well known that a large percentage of episodes of vomiting and diarrhea are really food poisoning and not the “flu” that is often blamed. For children and persons with MSUD, the vomiting and diarrhea that go with food poisoning can be disastrous. Be sure all foods that are to be refrigerated are not left at room temperature after a meal. Keep formula refrigerated between feedings. Keep dishes washed and use good hygiene. You may be able to avoid flu-like episodes that send MSUD children to the hospital.

2. ASPIRIN: Do not give aspirin or over-the-counter medications containing aspirin to children with MSUD. Children with MSUD are very susceptible to a Reye Syndrome-like illness with the accompanying brain edema. It is very important that children with MSUD do not take aspirin or products containing aspirin. Make it a practice to read the ingredient list on all over-the-counter medications.

3. VALPROIC ACID (valproate): Additional research is needed to determine the safety of medication containing valproate for children with MSUD. Valproic acid has been given to some children with MSUD for seizure activity. Several parents have noted significant changes in their children when this medication was given. These reactions disappeared when the medication was withdrawn. (See previous article and abstract.)

Have you noticed any adverse reactions to medications in your child with MSUD? Has any adult with MSUD had reactions? The editor would be interested in hearing from you and also from professionals who could give us some insight into medications and MSUD.

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