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.
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.