Margretta Reed Seashore MD

Professor of Genetics, of Laboratory Medicine, of Nursing and of Pediatrics; Director, Biochemical Disease Detection Laboratory

Research Interests

Clinical Genetics; Inborn errors of metabolism, diagnosis and treatment

Current Projects

  • 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

Research Summary

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.

Extensive Research Description

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.


Selected Publications

  • Waisbren SE, Albers S, Amato S, Ampola M, Brewster TG, Demmer L, Eaton RB, Greenstein R, Korson M, Larson C, Marsden D, Msall M, Naylor EW, Pueschel S, Seashore M, Shih VE, Levy HL. Effect of expanded newborn screening for biochemical genetic disorders on child outcomes and parental stress. JAMA. 2003 Nov 19;290(19):2564-72. PMID: 14625333 [PubMed - indexed for MEDLINE]
  • Waisbren SE, Read CY, Ampola M, Brewster TG, Demmer L, Greenstein R, Ingham CL, Korson M, Msall M, Pueschel S, Seashore M, Shih VE, Levy HL; New England Consortium of Metabolic Programs. Newborn screening compared to clinical identification of biochemical genetic disorders. J Inherit Metab Dis. 2002 Nov;25(7):599-600. PMID: 12638945 [PubMed - indexed for MEDLINE]
  • Seashore MR. Tetrahydrobiopterin and dietary restriction in mild phenylketonuria. N Engl J Med. 2002 Dec 26;347(26):2094-5. No abstract available. PMID: 12501220 [PubMed - indexed for MEDLINE]
  • Wood JC, Magera MJ, Rinaldo P, Seashore MR, Strauss AW, Friedman A. Diagnosis of very long chain acyl-dehydrogenase deficiency from an infant's newborn screening card. Pediatrics. 2001 Jul;108(1):E19. PMID: 11433098 [PubMed - indexed for MEDLINE]
  • Albers S, Waisbren SE, Ampola MG, Brewster TG, Burke LW, Demmer LA, Filiano J, Greenstein RM, Ingham CL, Korson MS, Marsden D, Schwartz RC, Seashore MR, Shih VE, Levy HL. New England Consortium: a model for medical evaluation of expanded newborn screening with tandem mass spectrometry. J Inherit Metab Dis. 2001 Apr;24(2):303-4. No abstract available. PMID: 11405349 [PubMed - indexed for MEDLINE]

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