The National Biennial Symposium for Maple Syrup Disease was held in June in Lancaster County with an overwhelming turnout of families and professionals from this country and overseas. Lectures and discussions followed the theme of "Progress, Problems, and Promises." Prior to the two day symposium for parents, the Clinic sponsored a day long scientific meeting to examine neurological effects of MSUD and to provide an overview of the clinic's approach to management of MSUD as presented in a first draft of a Manual for Care. Dr. Morton and Dr. Kevin Strauss, Resident in Pediatrics at Boston Children's Hospital who spent four months of his senior year of Harvard Medical School in study at the Clinic, discussed a "new" disease model for MSUD which recognizes the greater role of leucine as a modulator of amino acid transport into the brain and out of the cells. Much of the information presented at the Scientific Meeting was based upon work by Dr. Halvor Christensen who attended the meeting. Dr. Christensen remarked that some of his most important observations about how leucine influences the transport of other amino acids were made at Boston Children's Hospital in 1949. His early experiments led to the discovery of the transport system that regulates entry of the neutral amino acids into the brain and provided the first observations that increased concentrations of leucine and phenylalanine cause intracellular entrapment of selective amino acids. Dr. Christensen's discoveries are key to clearer understanding of how high serum leucine causes a complex neurologic syndrome that includes sudden changes in level of consciousness and coordination, brain edema, as well as chronic malnutrition of the developing nervous system. After Dr. Christensen's remarks, Dr. Morton and Dr. Strauss presented their studies of the neurological signs and MRI findings of acute leucine intoxication, described management protocols that allow recovery from cerebral edema, usually irreversible and fatal, and presented MRI findings of patients after prolonged imbalances in serum amino acids caused arrests of brain growth and development.
Douglas Wilmore, MD, Professor of Surgery, Harvard Medical School and Brigham & Women's Hospital in Boston discussed biochemical, endocrinologic, and inflammatory variables that must be controlled to prevent endogenous protein catabolism and sustain protein synthesis in ill or injured patients. His studies and recommendations of the use of glutamine in nutritional management were important contributions to the meeting.
Quentin R. Smith, PhD, Chairman, Department of Pharmacology, Texas Tech University, presented data about neutral amino acid transport across the blood brain barrier and what that suggests about acute neurological dysfunction and chronic amino acid deficiencies in the central nervous system of patients with MSUD.
Attended by approximately 35 physicians and researchers (including Dr. Hugo Moser of Kennedy Krieger Institute and an early supporter of the Clinic's work), the scientific session concluded with discussion of new strategies to prevent illness and injury in patients with MSUD. The current strategy, based on the central idea of simply lowering leucine to control MSUD, does not necessarily promote optimal growth and development. Children survive but are often compromised with some degree of malnutrition, poor brain growth, and mild to severe physical impairment. The new strategy developed by Dr. Morton and used by the Clinic seeks to balance the ratios of the amino acids leucine, isoleucine and valine by modifications in formulas and uses glutamine and alanine to help promote protein synthesis and catabolism in muscle and liver. This strategy has enabled many of the younger MSUD children in care by the Clinic to achieve and maintain normal growth and development.
Following the day long meeting, we enjoyed a Lancaster County supper graciously hosted by friends and neighbors, Marilyn Lewis and Marian Ware. We thank them for such a lovely evening to conclude our meeting.