I was inspired by Cindy Blau's story to look in the scientific literature for publications related to her case. Sure enough, "Maple Syrup Urine Disease with Particular Reference to Dietotherapy" was published in 1964 by Selma Snyderman, MD, Patricia M. Norton, Ellen Roitman, and L. Emmett Holt Jr. in the journal Pediatrics. This article details the journey taken by Cindy and her medical team as they tried new therapies to keep her alive.
As Cindy's older brother had died of MSUD, when she became difficult to feed and started to exhibit the classic maple syrup odor at the end of her first week of life, she was transferred to Bellevue Hospital in New York City where her amino acids were analyzed and levels of the branched-chain amino acids (BCAAs) were found to be elevated. By her 17th day of life, she was started on a special formula which omitted the BCAA along with methionine, which at that point was thought to also be involved in the metabolic abnormality.
At that time, formulas such as we have today did not exist. Cindy was given a synthetic mixture of amino acids along with vitamins, minerals, sugar, and corn oil. Within 3 days of starting this diet, Cindy began to improve.
With time, the team noticed that even slight elevations in temperature would cause Cindy's BCAA levels to rise and symptoms to recur. This was treated by removing the BCAAs along with methionine from the diet and adding fluids.
At about 6 months of age, Cindy stopped growing. The medical team felt that most likely there was an unknown nutritional factor that was missing from her synthetic diet, and decided to try her on a regular milk formula. Within 24 hours she became lethargic and lost muscle control. She did have a spurt of weight gain, but it was clear that she could not be managed on a regular formula, and her artificial formula was resumed.
When Cindy was 23 months of age, her doctors decided to give her a normal dose of the amino acid methionine along with a supplement of Brewer's yeast. This was effective at stimulating growth. Using a new method of amino acid analysis, it was determined that what was previously thought to be an elevation of methionine was actually alloisoleucine, a previously unknown amino acid made from isoleucine.
By manipulating the diet, Cindy's doctors were able to determine that isoleucine is responsible for the maple syrup smell while leucine is primarily responsible for neurological damage.
Cindy remained in Bellevue Hospital for four years, at which point she was finally discharged to her parent's care. The doctors noted that due to the unusual nature of her early years, which were spent in the hospital environment, she was not exposed to the language and experiences of other children. At the time this paper was written, she had recently been returned home and was attending a special needs school. At 5 years of age, Cindy was "sociable, articulate, energetic, and at times mischievous," and they held great hope for her future development.
MSUD treatment has come a long way since the 1960's, and we all owe a great deal to Cindy and her parents for everything they endured as they and their medical team learned together about how to treat this disease.
Treating MSUD: The Early Years
- Category: Volume 26-2