Genetic, Genomic and Metabolic Disorders

University Pediatricians | Michigan

About the Division of Genetic, Genomic and Metabolic Disorders

Using a multidisciplinary approach, the Division of Genetic, Genomic and Metabolic Disorders at the Children's Hospital of Michigan provides expert diagnosis, follow-up, treatment and counseling for infants, children and adults with genetic or suspected genetic disorders.  The Division is staffed by board-certified clinical geneticists, board-certified genetic counselors, specially trained nurses and nurse practitioners, dietitians, a social worker and a clinical psychologist. Faculty members are boarded in clinical genetics, biochemical genetics and molecular genetics.


In addition to providing diagnostic evaluations for individuals suspected of having a genetic condition and genetic counseling services for those identified with genetic conditions, there are numerous other programs operated by the Division of Genetic, Genomic and Metabolic Disorders. It is home to a newborn screening long term follow-up and treatment program for individuals diagnosed with an inborn error of metabolism following a positive newborn screen. The Children's Hospital of Michigan operates one of the few Lysosomal Storage Disease Clinics and Pediatric Enzyme Replacement Therapy (ERT) programs in Michigan treating children with lysosomal storage disorders and other genetic conditions treatable with enzyme replacement. The Division has also developed a Fetal Alcohol Syndrome Clinic for the diagnosis and management of children affected from intrauterine alcohol exposure. 

Leadership

Division Chief: David Stockton, MD

Genetic, Genomic & Metabolic Disorders Clinical Programs

  • Newborn Screening:

    Children’s Hospital of Michigan at is home to a lifelong follow-up and treatment program for individuals diagnosed with an inborn error of metabolism following a positive newborn screen. In Michigan, newborns are screened for approximately 50 different genetic disorders. Blood samples taken from the newborns shortly after birth are sent to the State of Michigan’s Newborn Screening Laboratory in Lansing for testing. Newborns that test positive for an inborn error of metabolism are referred to the Children’s Hospital of Michigan Metabolic Clinic, located within the Division of Genetic, Genomic and Metabolic Disorders, for confirmatory testing and, if needed, diagnosis and lifelong management.  Patients are seen at the Children’s Hospital of Michigan as well as at satellite locations in Southfield and Grand Rapids. A multidisciplinary team composed of physicians, metabolic dietitians, a genetic counselor, specially trained nurses and nurse practitioners, a social worker and psychologist work together to manage infants, children and adults with metabolic diseases.  Treatments are individualized for each metabolic disorder and may involve dietary management and/or medications.

  • Lysosomal Storage Disease Treatment Program (Enzyme Replacement Therapy):

    The Lysosomal Storage Disease Treatment Program is housed in the Division of Genetic, Genomic and Metabolic Disorders at the Children’s Hospital of Michigan.  The team of geneticists, nurse practitioner and genetic counselors work closely with pediatric cardiologists, ophthalmologists, orthopaedists, pulmonologists and other subspecialists to evaluate and treat children with lysosomal storage diseases.  Affected children typically lack an enzyme responsible for metabolizing or breaking down substances in the body.  If these substances accumulate to toxic levels, multi-organ damage occurs.   If left untreated, many lysosomal storage diseases result in serious medical complications and can be fatal. Enzyme replacement therapy (ERT) involves replacing the missing enzyme through intravenous infusions.  ERT is particularly effective if started early; many symptoms can be prevented, improved and/or eliminated.  Thus, early diagnosis and treatment of lysosomal storage diseases is critical.  A comprehensive evaluation is the initial step in diagnosis and subsequent treatment.

  • Fetal Alcohol Syndrome Clinic:

    The Division of Genetic, Genomic and Metabolic Disorders at the Children’s Hospital of Michigan has developed a Fetal Alcohol Syndrome Clinic.  Fetal alcohol syndrome (FAS) is caused by maternal consumption of alcohol during pregnancy.   FAS is characterized by pre and postnatal growth deficiency, a distinctive constellation of facial features, and developmental and behavioral problems. Not every child exposed to alcohol during the prenatal period will have FAS, but all children who have been exposed to alcohol in-uteroare at risk to have FAS or other developmental or behavioral problems. Any child who is suspected or known to have fetal alcohol syndrome can be referred to the clinic for in-depth evaluation, counseling and follow-up care.  Prior to the initial evaluation, the caregivers are asked to complete a questionnaire about the child’s medical and developmental histories. They are also asked to send copies of previous school and/or psychological evaluations to the clinic.  During the visit the Genetics team reviews the detailed medical and developmental histories, and performs a thorough physical examination on the child to determine if he/she has the features of FAS.   Based on the outcome of the initial visit, the clinic refers families to other ancillary services and treatment and provides follow-up care as needed.

  • Cystic Fibrosis Newborn Screening:

    Cystic fibrosis has been included in the State of Michigan’s newborn screening program since October 2007.  Once an infant screens positive for cystic fibrosis on newborn screening, they are referred to one of a few sites designated by the State of Michigan, of which the Children’s Hospital of Michigan is one, to provide confirmatory diagnosis and follow-up.  At the Children’s Hospital of Michigan, every infant with a positive newborn screen has access to the appropriate diagnostic testing and genetic counseling services, which are typically offered as coordinated appointments on the same day.  If an infant is diagnosed with cystic fibrosis, the Division provides comprehensive genetic counseling services to these families to help them understand the genetics of cystic fibrosis and what it means for their children, themselves and their extended families.

  • Hemophilia Clinic:

    The Division also works with the Division of Hematology/Oncology to provide genetic services for families with hemophilia or other inherited clotting disorders.   The department works with the Hemophilia Clinic team to provide genetic evaluation and counseling services, an essential component of the comprehensive services they receive.  Extensive genetic counseling and the option of genetic testing for all newly diagnosed families is offered.  Genetic counseling services to anyone regularly followed through the Hemophilia Clinic who has specific questions regarding the genetics of hemophilia or their specific diagnosis is also provided.

Faculty

Faculty


Advanced Practice Providers

  • Linda Spencer, CNNP
  • Taylor Tucker, NP
  • Brooke Wanshon, CNNP

Want to learn more about our distinguished specialists? Click the button below to be taken to our Faculty Directory.

Faculty Directory →

Education

The Division of Genetic, Genomic and Metabolic Disorders trains numerous students, residents and fellows from programs in the Metropoitan Detroit area and around the world. It is a clinical rotation site for students from the Wayne State University Genetic Counseling Graduate Program. Working with Wayne State University School of Medicine, it provides training and education for the combined Pediatric/Genetics Residency Program, the Medical Genetics Fellowship Program and is one of the few sites in the country offering a Medical Biochemical Genetics Fellowship program.

Learn more about the residency program and fellowships offered in affiliation with the Children's Hospital of Michigan.

Research

Recent Faculty Publications

  • Robert Conway, MD

    • Longo N, Diaz GA, Lichter-Konecki U, Schulze A, Inbar-Feigenberg M, Conway RL, Bannick AA, McCandless SE, Zori R, Hainline B, Ah Mew N, Canavan C, Vescio T, Kok T, Porter MH, Berry SA. Glycerol phenylbutyrate efficacy and safety from an open label study in pediatric patients under 2 months of age with urea cycle disorders. Mol Genet Metab. 2020 Dec 23:S1096-7192(20) 30270-5.  Dr. Conway was one of the site principal investigators for this industry sponsored post-marketing clinical trial which sought to establish Ravicti dosing safety for neonates affected with urea cycle disorders. In addition to his role as site PI, he assisted in manuscript review.
    • Bannick A, Chase S, Miner A, Seeterlin M, Conway RL. Methionine Adenosyltransferase I/III Deficiency: Long-Term Follow-up and Treatment of 3 Adult Siblings. Eur J Med Genet. 2020 Sep 24:104076.   Dr. Conway was the senior faculty mentor for this project primarily authored by Bannick.
    • Ames EG, Scott AJ, Pappas KB, Maoney SM, Conway RL, Ahmad A. A cautionary tale of pyridoxine toxicity in cystathionine beta-synthase deficiency detected by two-tier newborn screening highlights the need for clear pyridoxine dosing guidelines. Amer J of Med Genetics A. 2020 Aug 20.  Dr. Conway contributed to this project by providing clinical data pertinent to 2nd tier data analysis from the state newborn screening program to the primary author, manuscript review, editing, and substantive contribution to the text.

  • Vinod Misra, MD

    • *Doctor P, Sood BG, Natarajan G, Misra VK. (2020). Rib Fracture in a Term Newborn with Respiratory Distress. NeoReviews. Jul 2020. In press.
    • *Chand MT, Turner S, Solomon LA, Jay A, Rabah R, Misra VK. (2020) A Case of 45,X/46,XY Mosaicism Presenting as Swyer Syndrome. Journal of Pediatric and Adolescent Gynecology. 33(5):577-580. (doi: 10.1016/j.jpag.2020.06.008).
    • Gunning AC, Strucinska K, Oreja MM, Parrish A, Caswell R, Stals KL, Durigon R, Durlacher-Betzer K, Cunningham MH, Grochowski CM, Baptista J, Tysoe C, Baple E, Lahiri N, Homfray T, Scurr I, Armstrong C, Dean J, Pelayo UF, Jones AWE, Taylor RW, Misra VK, Yoon WH, Wright CF, Lupski JR, Spinazzola A, Harel T, Holt IJ, Ellard, S. (2020). Recurrent De Novo NAHR Reciprocal Duplications in the ATAD3 Gene Cluster Cause a Neurogenetic Trait with Perturbed Cholesterol and Mitochondrial Metabolism. The American Journal of Human Genetics. 106 (2): 272-279.

  • Kara Pappas, MD

    • Singh P, Secord E, Pappas K, Savaşan S.. An infant with severe combined immunodeficiency, osteopetrosis, chromosomally integrated herpesvirus-6 infection, and hemophagocytic syndrome: What are the links? Pediatr Blood Cancer 2020 Aug;e28564. doi: 10.1002/pbc.28564
    • Ames EG, Scott AJ, Pappas KB, Moloney SM, Conway RL, Ahmad A. A cautionary tale of pyridoxine toxicity in cystathionine beta-synthase deficiency detected by two-tier newborn screening highlights the need for clear pyridoxine dosing guidelines. Am J Med Genet A. 2020 Aug. doi: 10.1002/ajmg.a.61815.
    • Kaur S, Pappas K. Genetic Etiologies of Neonatal Seizures. Neoreviews (10) 2020:e663-e672. doi: 10.1542/neo.21-10-e663.

  • David Stockton, MD

    • Respiratory function during enzyme replacement therapy in late-onset Pompe disease: longitudinal course, prognostic factors, and the impact of time from diagnosis to treatment start. Stockton DW, Kishnani P, van der Ploeg A, Llerena J Jr, Boentert M, Roberts M, Byrne BJ, Araujo R, Maruti SS, Thibault N, Verhulst K, Berger KI. J Neurol. 2020 Oct;267(10):3038-3053. doi: 10.1007/s00415-020-09936-8. Epub 2020 Jun 10. PMID: 32524257 Free PMC article.
    • Deficiency of FRAS1-related extracellular matrix 1 (FREM1) causes congenital diaphragmatic hernia in humans and mice. Beck TF, Veenma D, Shchelochkov OA, Yu Z, Kim BJ, Zaveri HP, van Bever Y, Choi S, Douben H, Bertin TK, Patel PI, Lee B, Tibboel D, de Klein A, Stockton DW, Justice MJ, Scott DA. Hum Mol Genet. 2020 Apr 15;29(6):1054. doi: 10.1093/hmg/ddz307. PMID: 32016392 No abstract available.
    • Clinical spectrum of individuals with pathogenic NF1 missense variants affecting p.Met1149, p.Arg1276, and p.Lys1423: genotype-phenotype study in neurofibromatosis type 1. Koczkowska M, Callens T, Chen Y, Gomes A, Hicks AD, Sharp A, Johns E, Uhas KA, Armstrong L, Bosanko KA, Babovic-Vuksanovic D, Baker L, Basel DG, Bengala M, Bennett JT, Chambers C, Clarkson LK, Clementi M, Cortés FM, Cunningham M, D'Agostino MD, Delatycki MB, Digilio MC, Dosa L, Esposito S, Fox S, Freckmann ML, Fauth C, Giugliano T, Giustini S, Goetsch A, Goldberg Y, Greenwood RS, Griffis C, Gripp KW, Gupta P, Haan E, Hachen RK, Haygarth TL, Hernández-Chico C, Hodge K, Hopkin RJ, Hudgins L, Janssens S, Keller K, Kelly-Mancuso G, Kochhar A, Korf BR, Lewis AM, Liebelt J, Lichty A, Listernick RH, Lyons MJ, Maystadt I, Martinez Ojeda M, McDougall C, McGregor LK, Melis D, Mendelsohn N, Nowaczyk MJM, Ortenberg J, Panzer K, Pappas JG, Pierpont ME, Piluso G, Pinna V, Pivnick EK, Pond DA, Powell CM, Rogers C, Ruhrman Shahar N, Rutledge SL, Saletti V, Sandaradura SA, Santoro C, Schatz UA, Schreiber A, Scott DA, Sellars EA, Sheffer R, Siqveland E, Slopis JM, Smith R, Spalice A, Stockton DW, Streff H, Theos A, Tomlinson GE, Tran G, Trapane PL, Trevisson E, Ullrich NJ, Van den Ende J, Schrier Vergano SA, Wallace SE, Wangler MF, Weaver DD, Yohay KH, Zackai E, Zonana J, Zurcher V, Claes KBM, Eoli M, Martin Y, Wimmer K, De Luca A, Legius E, Messiaen LM.  Hum Mutat. 2020 Jan;41(1):299-315. doi: 10.1002/humu.23929. Epub 2019 Oct 26. PMID: 31595648 Free PMC article.
    • Thrombotic risk in congenital erythrocytosis due to up-regulated hypoxia sensing is not associated with elevated hematocrit.Gordeuk VR, Miasnikova GY, Sergueeva AI, Lorenzo FR, Zhang X, Song J, Stockton DW, Prchal JT.  Haematologica. 2020 Mar;105(3):e87-e90. doi: 10.3324/haematol.2019.216267. Epub 2019 Jul 9. PMID: 31289208 Free PMC article. No abstract available.

Recent Faculty Abstracts/Presentations (National)

  • Gerald Feldman, MD

    • Sen K, Kaur S, Friday, Y, Cichon, M, Smitherman, L, Feldman, GL. Genetics Primary Care Clinic Initiated By Combined Pediatric-Medical Genetics And Genomics Residents: A Potential National Model. American College of Medical Genetics and Genomics 2020 Annual Meeting. Genet Med (on line). Platform Presentation. 
    • Dasgupta S, Feldman GL, Powell C, Toriello H, Westman J, Wilson W, Waggoner D. Training the Next Generation Of Genomic Medicine Providers: Trends In Medical Education And National Assessment. American College of Medical Genetics and Genomics 2020 Annual Meeting. Genet Med (on line). Platform Presentation 

  • Vinod Misra, MD

    • Pomerantz DJ, Cunningham, MH, Altinok, D & Misra, VK. (2020) BCAP31- Associated Encephalopathy Presenting as Early Infantile Spastic Paraplegia, American College of Medical Genetics 2020 Annual Clinical Genetics Meeting, San Antonio, TX.

  • Kara Pappas, MD

    • Henige H, Kaur S, Pappas K. “Compound Heterozygous Variants In GOSR2 Associated With Congenital Muscular Dystrophy: A Case Report.” Poster presented American College of Medical Genetics and Genomics Annual Meeting; 2020 Mar 17-21; San Antonio, TX 
    • Pomerantz D, Hankerd M, Campbell S, Smith-Dewey R, Ebrahim S, Pappas K. “Severe Respiratory Distress, Chronic Constipation & Absence of Thrombocytopenia as Distinguishing Features in a Case of 10p12-p11 Microdeletion Syndrome.” Poster presented American College of Medical Genetics and Genomics Annual Meeting; 2020 Mar 17-21; San Antonio, TX

Recent Faculty Grants

  • Robert Conway, MD

    “An Open-label Extension Study to Evaluate the Safety and Efficacy of Subcutaneous Injections of Pegvaliase (> 40 mg/day Dose) in Adults with Phenylketonuria” 

    The aim of this trial is to assess the safety of pegvaliase doses higher than that presently approved by the FDA; subjects in this study were rolled over from study BMN 165-302. Role: Site PI for multi-center trial Funding Source/Sponsor: Biomarin Pharmaceutical 

    Time Period: 12/6/2018-February 2020 Funding source: Biomarin Pharmaceutical. Direct cost $33,592

  • Gerald Feldman, MD

    Program Director and Principal Investigator, Michigan Department of Community Health: Newborn Screening Management Program. Annual contract, effective 10/1/20-9/30/21, awarded to Children’s Hospital of Michigan, Division of Genetic and Metabolic Disorders, for the management of all infants born in Michigan and diagnosed with an inborn error of metabolism through the Newborn Screening Program; (Budget: $2,027,231) 


    Program Director and Principal Investigator, Michigan Department of Community Health: Special Supplemental Nutrition Program for Women, Infants and Children (WIC), contract, effective 10/1/20- 9/30/21, awarded to Children’s Hospital of Michigan, Division of Genetic and Metabolic Disorders, for the management of infants born in Michigan and diagnosed with an inborn error of metabolism through the Newborn Screening Program; (Budget: $11,745)


     Program Director and Principal Investigator, Michigan Department of Community Health: Newborn Screening Management Program. Annual contract, effective 10/1/19-9/30/20, awarded to Children’s Hospital of Michigan, Division of Genetic and Metabolic Disorders, for the management of all infants born in Michigan and diagnosed with an inborn error of metabolism through the Newborn Screening Program; (Budget: $1,972,251)


    Program Director and Principal Investigator, Michigan Department of Health and Human Services: Special Supplemental Nutrition Program for Women, Infants and Children (WIC) contract, effective 10/1/19-9/30/20, awarded to Children’s Hospital of Michigan, Division of Genetic, Genomic and Metabolic Disorders, for the management of infants born in Michigan and diagnosed with an inborn error of metabolism through the Newborn Screening Program (Budget: $11,745) 

  • David Stockton, MD

    State of Michigan Newborn Screening Lysosomal Storage Disease Coordinating Center A Long-Term Study to Evaluate Growth and Development Outcomes in Patients with Infantile-Onset Pompe Disease who are Receiving Myozyme (Alglucosidase Alfa)


    Fetal Alcohol Syndrome Diagnostic Clinic from the Michigan Department of Health and Human Services 


    Genetic Services Grant from the Michigan Department of Health and Human Services 

Recent Faculty Awards & Other Professional Accomplishments

  • Kara Pappas, MD

    Other Professional Accomplishments:

    • American College of Medical Genetics, Education Committee, Member

  • David Stockton, MD

    Awards:

    • Hour Magazine "Top Doc" 2020
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