Biochemical Phenomena; Genetic Counseling; Genetics; Metabolism, Inborn Errors; Pediatrics; Prenatal Diagnosis; Medical Laboratory Science
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
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.
- 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
Effect of expanded newborn screening for biochemical genetic disorders on child outcomes and parental stress.
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, 290:2564-72. 2003
Newborn screening compared to clinical identification of biochemical genetic disorders.
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. Newborn screening compared to clinical identification of biochemical genetic disorders. Journal Of Inherited Metabolic Disease 2002, 25:599-600. 2002
Tetrahydrobiopterin and dietary restriction in mild phenylketonuria.
Seashore MR. Tetrahydrobiopterin and dietary restriction in mild phenylketonuria. The New England Journal Of Medicine 2002, 347:2094-5. 2002
Diagnosis of very long chain acyl-dehydrogenase deficiency from an infant's newborn screening card.
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, 108:E19. 2001
New England Consortium: a model for medical evaluation of expanded newborn screening with tandem mass spectrometry.
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. Journal Of Inherited Metabolic Disease 2001, 24:303-4. 2001
Full List of PubMed Publications
- Rojnueangnit K, Xie J, Gomes A, Sharp A, Callens T, Chen Y, Liu Y, Cochran M, Abbott MA, Atkin J, Babovic-Vuksanovic D, Barnett CP, Crenshaw M, Bartholomew DW, Basel L, Bellus G, Ben-Shachar S, Bialer MG, Bick D, Blumberg B, Cortes F, David KL, Destree A, Duat-Rodriguez A, Earl D, Escobar L, Eswara M, Ezquieta B, Frayling IM, Frydman M, Gardner K, Gripp KW, Hernández-Chico C, Heyrman K, Ibrahim J, Janssens S, Keena BA, Llano-Rivas I, Leppig K, McDonald M, Misra VK, Mulbury J, Narayanan V, Orenstein N, Galvin-Parton P, Pedro H, Pivnick EK, Powell CM, Randolph L, Raskin S, Rosell J, Rubin K, Seashore M, Schaaf CP, Scheuerle A, Schultz M, Schorry E, Schnur R, Siqveland E, Tkachuk A, Tonsgard J, Upadhyaya M, Verma IC, Wallace S, Williams C, Zackai E, Zonana J, Lazaro C, Claes K, Korf B, Martin Y, Legius E, Messiaen L: High Incidence of Noonan Syndrome Features Including Short Stature and Pulmonic Stenosis in Patients carrying NF1 Missense Mutations Affecting p.Arg1809: Genotype-Phenotype Correlation. Hum Mutat. 2015 Nov; 2015 Aug 21. PMID: 26178382
- Chan O, Paranjape S, Czyzyk D, Horblitt A, Zhu W, Ding Y, Fan X, Seashore M, Sherwin R: Increased GABAergic output in the ventromedial hypothalamus contributes to impaired hypoglycemic counterregulation in diabetic rats. Diabetes. 2011 May; 2011 Mar 16. PMID: 21411513
- Zhu W, Czyzyk D, Paranjape SA, Zhou L, Horblitt A, Szabó G, Seashore MR, Sherwin RS, Chan O: Glucose prevents the fall in ventromedial hypothalamic GABA that is required for full activation of glucose counterregulatory responses during hypoglycemia. Am J Physiol Endocrinol Metab. 2010 May; 2010 Feb 9. PMID: 20304763
- Rossi MR, DiMaio MS, Xiang B, Lu K, Kaymakcalan H, Seashore M, Mahoney MJ, Li P: Clinical and genomic characterization of distal duplications and deletions of chromosome 4q: study of two cases and review of the literature. Am J Med Genet A. 2009 Dec. PMID: 19921640
- Bultron G, Seashore MR, Pashankar DS, Husain SZ: Recurrent acute pancreatitis associated with propionic acidemia. J Pediatr Gastroenterol Nutr. 2008 Sep. PMID: 18728537
- Chan O, Cheng H, Herzog R, Czyzyk D, Zhu W, Wang A, McCrimmon RJ, Seashore MR, Sherwin RS: Increased GABAergic tone in the ventromedial hypothalamus contributes to suppression of counterregulatory responses after antecedent hypoglycemia. Diabetes. 2008 May; 2008 Mar 28. PMID: 18375441
- Bilguvar K, Bydon M, Bayrakli F, Ercan-Sencicek AG, Bayri Y, Mason C, DiLuna ML, Seashore M, Bronen R, Lifton RP, State M, Gunel M: A novel syndrome of cerebral cavernous malformation and Greig cephalopolysyndactyly. Laboratory investigation. J Neurosurg. 2007 Dec. PMID: 18154020
- Seashore MR, Seashore CJ: Newborn screening and the pediatric practitioner. Semin Perinatol. 2005 Jun. PMID: 16114581
- Seashore MR: Tetrahydrobiopterin and dietary restriction in mild phenylketonuria. N Engl J Med. 2002 Dec 26. PMID: 12501220
- Chen L, Vaezy A, Seashore MR, Baum CR: Emesis, confusion, and visual loss in an adolescent. Pediatr Case Rev. 2002 Oct. PMID: 12865672