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The MMWR series of publications is published by the Introduction 1. Epidemiology Program Office Centers for Disease, Control and Prevention CDC U S Department of Background 2. Health and Human Services Atlanta GA 30333 Clinical Characteristics and Effect of PI Diseases 3. Incidence and Birth Prevalence Estimates 7, SUGGESTED CITATION Diagnosis 7. Centers for Disease Control and Prevention Applying. public health strategies to primary immunodeficiency Treatment 8. diseases a potential approach to genetic disorders Public Health Framework 9. MMWR 2004 53 No RR 1 inclusive page numbers Public Health Assessment 10. Population Based Interventions 13, Evaluation of Screening and Diagnostic Tests 18. Centers for Disease Control and Prevention Education and Communication 21. Julie L Gerberding M D M P H Conclusion 22, References 22. Dixie E Snider Jr M D M P H Terms and Abbreviations Used in This Report 26. Acting Deputy Director for Public Health Science, Continuing Education Activity CE 1.
Susan Y Chu M D M S P H, Acting Associate Director for Science. Epidemiology Program Office, Stephen B Thacker M D M Sc. Office of Scientific and Health Communications, John W Ward M D. Editor MMWR Series, Suzanne M Hewitt M P A, Managing Editor MMWR Series. C Kay Smith Akin M Ed, Lead Technical Writer Editor.
Project Editor, Beverly J Holland, Lead Visual Information Specialist. Lynda G Cupell, Malbea A LaPete, Visual Information Specialists. Kim L Bright M B A, Quang M Doan M B A Disclosure of Relationship. Erica R Shaver Our subject matter experts wish to disclose they have no financial. Information Technology Specialists interests or other relationships with the manufacture of commercial. products providers of commercial services or commercial supporters. This report does not include any discussion of the unlabeled use of. commercial products or products for investigational use. Vol 53 RR 1 Recommendations and Reports 1, Applying Public Health Strategies. to Primary Immunodeficiency Diseases, A Potential Approach to Genetic Disorders.
Prepared by, Mary Lou Lindegren M D 1 Lisa Kobrynski M D 2 Sonja A Rasmussen M D 3 Cynthia A Moore M D Ph D 3 Scott D Grosse Ph D 4. Marsha Lynne Vanderford Ph D 5 Thomas J Spira M D 6 J Steven McDougal M D 6 Robert F Vogt Jr Ph D 7 W Harry Hannon Ph D 7. Lisa V Kalman Ph D 7 Bin Chen Ph D 8 Marifran Mattson Ph D 9 Timothy G Baker M P H 1 and Muin Khoury M D Ph D 1. Office of Genomics and Disease Prevention National Center for Environmental Health CDC 2Emory University Atlanta Georgia 3Division of Birth Defects. and Developmental Disabilities National Center on Birth Defects and Developmental Disabilities CDC 4Office of the Director National Center on Birth. Defects and Developmental Disabilities CDC 5Office of the Director National Center for Environmental Health 6Division of AIDS STD and TB. Laboratory Research National Center for HIV STD and TB Prevention CDC 7Division of Laboratory Sciences National Center for Environmental Health. CDC 8Division of Laboratory Systems Public Health Practice Program Office CDC and 9Purdue University West Lafayette Indiana. Primary immunodeficiency PI diseases are a group of primarily single gene disorders of the immune system Approximately. 100 separate PI diseases have been described but 20 probably account for 90 of cases Although diverse PI diseases share the. common feature of susceptibility to infection and result in substantial morbidity and shortened life spans Most important. prompt diagnosis and treatment can now lead to life saving treatment and result in marked improvements in the quality and. length of life for persons with PI diseases, In November 2001 a workshop was convened by CDC in Atlanta Georgia to discuss ways to improve health outcomes among. persons with PI disease A multidisciplinary panel of persons knowledgeable in PI diseases and public health met to identify and. discuss public health strategies that can be applied to PI diseases and possibly for other genetic disorders A systematic assessment. based on the established public health framework was applied to the growing group of PI diseases whose diverse genetic mutations. span multiple components of the immune system but all lead to increased incidence and severity of infections. During the meeting specialists in clinical immunology public health genetics pediatrics health communication and ethics. from state and federal agencies academic centers professional organizations and advocacy foundations discussed the four compo. nents of the public health framework as they relate to PI diseases These four components include 1 public health assessment. application of traditional public health methods to assess the occurrence and impact of PI diseases on communities 2 population. based interventions development implementation and evaluation of screening tests administered to newborns and clinical. algorithms for early recognition of symptomatic persons to facilitate the earliest possible diagnosis and treatment for PI diseases. 3 evaluation of screening and diagnostic tools to ensure their quality and appropriateness for identification of patients with PI. diseases and 4 communication communication with and information dissemination to health care providers and the public to. facilitate prompt and appropriate diagnosis and intervention The working group s deliberations focused on challenges and. opportunities priority research questions and recommendations for future action for these four components These recommenda. tions developed by workshop participants will be useful to medical and public health professionals who are evaluating methods. to increase recognition of PI diseases and other genetic disorders. Introduction, The material in this report originated in the National Center for. Environmental Health Richard J Jackson M D Director the Office Advances in human genetics and the evolution of the. of Genomics and Disease Prevention Muin J Khoury M D Ph D Human Genome Project will play a central role in the prac. Director and the Division of Laboratory Sciences Eric J Sampson. Ph D Director the National Center on Birth Defects and. tice of medicine and public health in the 21st century How. Developmental Disabilities Jos F Cordero M D Director and the ever gene discovery is only the beginning For the majority of. Division of Birth Defects and Developmental Disabilities Gilberto diseases a gap exists between discovering or sequencing genes. Chavez M D Director the National Center for HIV STD and TB and using human genomic information to improve health. Prevention Harold W Jaffe M D Director and the Division of. AIDS STD and TB Laboratory Research Jonathan E Kaplan M D outcomes 1 Public health research and policy have a crucial. Director and the Public Health Practice Program Office Suzanne role in closing that gap Moving from gene discovery to clini. Smith M D Acting Director and the Division of Laboratory Systems cal and public health application requires full engagement of. Robert Martin Dr P H Director, public health to 1 quantify the effect of genetic discoveries. 2 MMWR January 16 2004, on population health 2 develop policies regarding and guide Examples of such single gene disorders are cystic fibrosis CF.
lines for the appropriate use of genetic tests and services and phenylketonuria PKU Single gene disorders can be. 3 develop interventions to improve health outcomes 4 ini either X linked i e caused by a defect in a gene on the X. tiate and maintain behavior change among patients and health chromosome or autosomal i e caused by a defect in a gene. care providers and 5 address the quality of and access to on an autosome or nonsex chromosome Single gene disor. services Genomic breakthroughs have been identified as ders can result from either dominant or recessive patterns of. major challenges for public health in the 21st century 2 inheritance or expression Selected chromosomal disorders. However the usefulness of these breakthroughs in clinical which might be inherited involve microdeletions of multiple. practice depends on the availability of population based data genes at closely linked loci Although single gene disorders. to determine the prevalence of gene variants among different are individually rare they collectively contribute to a substan. populations the population based risk for disease associated tial proportion of pediatric morbidity and mortality 1. with gene variants gene environment interactions and the PI diseases are a group of primarily single gene disorders of. effectiveness of genetic tests and services 3 5 the immune system 11 13 Primary denotes the genetic. As part of efforts to highlight the emerging role of human nature of the defects differentiating them from secondary or. genomics in the practice of public health in the United States acquired immunodeficiencies caused by malnutrition infec. CDC in collaboration with research academic clinical and tion e g human immunodeficiency virus HIV infection. foundation partners evaluated public health strategies that chemotherapy or other external agents Approximately 100. can be used to close the gap between gene discoveries and separate PI diseases have been described but 20 probably. clinical practice for primary immunodeficiency PI diseases account for 90 of cases The disorders vary in the severity. approximately 100 primarily single gene disorders of the and spectrum of symptoms but without effective and early. immune system Identification of the genes responsible for treatment they can be fatal A high index of suspicion and. these conditions is progressing rapidly therefore a population prompt diagnosis can lead to lifesaving treatment and sub. based framework is needed that can be applied also to other stantial improvement in quality of life for persons with PI. genetic disorders and gene discoveries This report describes the diseases Causes of PI diseases vary but single gene defects. concerns challenges and opportunities and provides can lead to a missing enzyme a missing structural compo. recommendations for public health action regarding such a nent developmental arrest at a specific differential stage of. framework immune development or a nonfunctional protein As with. all single gene disorders selected PI diseases are known to be. X linked or autosomal with both dominant and recessive. Background patterns of inheritance or de novo mutations others might. With completion of the Human Genome Project 30 000 have more complex modes of inheritance not yet understood. 35 000 genes have been mapped 6 9 each of which con Approximately 80 of affected persons are aged 20 years. tains the code for a specific product typically a protein and because certain PI diseases are inherited in X linked. Through the proteins they encode genes determine and regu recessive fashion 70 of cases occur among males 13. late all human body processes Human genomics includes a Advances in human genomics have led to identification of. continuum from the study of single gene disorders with high the gene defects responsible for 60 PI diseases and have. penetrance to common genetic variants or polymorphisms at prompted development of new diagnostic and therapeutic tools. multiple loci with low penetrance and that have complex and potential gene therapies 14 20 New molecular tech. gene environment interactions 10 Genetic disorders are niques have facilitated identification of different types of. caused by mutations or alterations in a gene or set of genes mutations underlying PI diseases Single nucleotide substitu. Mutations can be inherited or occur de novo The effect of a tions or point mutations involve an alteration in the sequence. mutation on a gene depends on how it alters the expression or of nucleotides in a gene These include missense mutations. function of the gene product and the role of that protein in which alter the amino acids in the protein product of a gene. the body Mutations in certain genes have severe effects nonsense mutations which generate premature stop codons. whereas mutations in others do not in the genetic code RNA ribonucleic acid splice site muta. The majority of genetic disorders result from a complex tions which can lead to frameshift mutations and regulatory. interplay of multiple genetic changes and environmental fac mutations which affect aspects of gene expression Mutations. tors However certain disorders result when a mutation alters also can involve insertions or deletions of DNA deoxyribo. or causes an absence of the product of only one gene nucleic acid sequences Progress in the delineation of the. Vol 53 RR 1 Recommendations and Reports 3, mechanisms by which these genetic mutations cause PI dis infections For reasons not completely understood the inci. eases has added to the understanding of the normal immune dence of allergy or autoimmune disease is increased among. system and the processes that underlie conditions that occur patients with selective IgA deficiency Certain IgA. with far greater frequency than PI disease 21 deficient persons might have severe or fatal anaphylactic. reactions to blood or blood products containing IgA. Clinical Characteristics and Effect Combined B and T Cell Deficiencies. of PI Diseases Combined B cell and T cell immunodeficiencies constitute. The clinical hallmark of PI diseases is an increased suscepti approximately 20 of PI diseases 23 In the most serious. bility to infection the severity of which varies by defect 13 22 forms e g severe combined immunodeficiency SCID dis. Centers for Disease Control and Prevention Applying public health strategies to primary immunodeficiency diseases a potential approach to genetic disorders MMWR 2004 53 No RR 1 inclusive page numbers The MMWR series of publications is published by the Epidemiology Program Office Centers for Disease Control and Prevention CDC U S

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