Margretta Seashore, MD

The success of treatment of inborn errors of metabolism depends upon early diagnosis and effective long-term management. We are concerned with improving the treatment of these genetic disorders. Our activities include diagnosis and screening, therapy, prenatal diagnosis and genetic counseling.

Specialized Terms: Clinical Genetics; Inborn errors of metabolism, diagnosis and treatment

Our interest is in the delineation and characterization of a number of inherited disorders of clinical importance. These include inborn errors of metabolism, single gene disorders, and certain other disorders with a genetic component.

With the support of the New England Regional Genetics Group we are looking at the factors which favor collaboration among metabolic specialists who care for children and adults with inherited disorders of metabolism. We are looking at collaborative treatment protocols, diagnostic strategies, and process and outcomes of newborn screening. The data implicate a false positive newborn screening test as a significant cause of anxiety in new parents, suggesting that prompt assessment and confirmatory testing are crucial in the evaluation of abnormal newborn screening results.

We are one 25 worldwide research sites conducting a clinical trial to study the effectiveness of a tetrahydrobiopterin, (BH4) a new investigational drug to lower the levels of phenylalanine (Phe) in the blood of persons diagnosed with phenylketonuria (PKU). We hope to learn whether or not this investigational drug will be effective to lessen some of the dietary restrictions necessary to lower the concentration of phenylalanine in the blood to acceptable treatment levels. This study is being done in the General Clinical Research Center at Yale New Haven Hospital in New Haven.

We are collaborators in a multi-center consortium working to develop a clinical registry of patients with all urea cycle disorders. This effort is part of an NIH-sponsored Rare Diseases Clinical Research Network (RDCRN). An important aspect of this effort is a longitudinal study of outcome in urea cycle disorders. The goal of this study is to identify all of the patients in the North America and determine clinical outcomes, efficacy of treatment and the importance of timing of diagnosis.

• Clinical trial to study the effectiveness of a tetrahydrobiopterin, (BH4) a new investigational drug to lower the levels of phenylalanine (Phe) in the blood of persons diagnosed with phenylketonuria (PKU).

• Longitudinal study on outcome of urea cycle disorders.
• Hepatocyte transfer in urea cycle disorders