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ij ) 1 ,pcctinim szsams l's 722 PS 009 601- r. .. , ' Boltzman4 Neil AO , ./ 1 Newborn Screening for Genetic-detabolic-DiseaSes: ?Its Progress, Principles and Recommendations.. INSTITUTION Bealth,Services Adainistratioft (DREMPOS),Rockville, Nd. Bureau of coinunity HeAlth Services. - . , IMPORT NO . DREW -RSI.4-77=5207 _ PUB DATE .- . 728p. , EDRS PRICE' BF -10.83 RC-$2..06 ,Plui Postage.. 4='DEICR/PTORS *Dideises; Ethics; Infmnts; *Laboratory Techniques; Legal Respongibiiity; Mental Retardatichn; *Neonates; Organization; '*Screening Tests IDENTIFIERS *Phenylketonuria , a. A . , ABSTRACT. This nonogragh, designedfoi.personvinvolved in the organization ands regulation of.screening.o4 newborns infants for Pbenylketonuria. OD) and other genetic-metabolic diseases reviews . new developments in. the field, makesreconmendations, and provides infornation about specific conditions other than Pica. that are . .d'etectable by screening. Discussed briefly ir"Part I a -rd various iN aipects_ot screening for PAO, ethical and legal, issues and Screening fir other conditions. Part IS suggests a model for supervisinei . screening operations for any disorder' (from determining 'what conditions should be for, through implementation to evaluation); discusses laboritory responsibilities-and offers . specific recoiaendations regarding PEN screening. Part 41 lists. conditiots that can be screened for,with four different procedures. ,(SB) , . , , p -) 4. *3110#4120***4**********11******3-01*********f************#*Mili************** . * Dgcunentsacquired by ERIC include many infbrnal unpublished * .* materials'not available from sources. ,ERIC makes every effort * * o obtain the best copy avai,ible..Nevertheless, iteas of Marginal * - *reprOdivcibility are often encounteredandthis affect's the-quality '* 40/tof the microfickWand hardcopy reptoductions.ERIC mates availabl4 * * via the ERIC Dodunent Bleproductidn Service (EDRS). EDRSis not . * '* responsible for the finality of the original document.,Reproductions * * supplied,by,EDRS are the best that can be made fro* the original. *. ********104*************v**************************************v******* 1 ) -1 (r .. u, DEPARTMENT OF HEALTH. EDUCA.TIONAWELFARE NEWBORN: NATIONAL INSINSTITUTE OF EDUCATION -- THIS DOCUMENT S !WEN REPRJO- OUCED EXACTLY A FR CR-EENING THE PERSON OR ORGANIZRECEIVEDATIONORIGINOM- ATING IT POINTS oi,,viEw OR OPINIONS STATED DO NOT NECESSARILY REPRE. SENT OFFICIAL NATIONAL INSTITUTE OF FOR ...._ EDUCATION POSITION OR POLICY C., It el IMF HEALTH, E04.1CAT10141 MD WELFME . Conterits o., Foreword e. iv Part I:New Developments,\t, 1 PhenylketonuriaPrognosis1 1 Transient elevations and variants 1. False negatives 2 Laboratory error 2 Delays 0"- 2 Unre'solved problems 2 Ethical and Legal Issues-- 3 Informed consent, 3 it 1 Right to informapori 3 Regulatiim of screening 4 .Regionalization 4 , Li Screening for Other Conclilio' ns 5 PartII. Recdmmendations ,7 A Cintral Organization for _Screening Determine which conditions should be screeneirktor 7 Determine: procedure; for collectionof) specimens 8 Determine procedures for transmission of specirirlos and results,recording of data 8 Determine adequacy oflaboratory(or laboratories) in the §tate 8 4/4 Referral Center 8 Educition and infortnation 8 Determine informed, consent procedures Evaluation 9 ii Or % A' *4.....- .P 1 . Laboratory Responsibilities 9 Quality control . 9 Determination ofthe cutoff point and optimal age for testing il 11 Storage of specimens ,.,',--- 12 ) Recording of results 2 12 -, .. Evaluation of tests fornew conditions and new tests 8 ,.. ,- 12 Recommendations for Screening forPhenylketonuriaL-- 13 Information and consent j3 ) Timing of the test 1,3 ) 't Responsibility for testing 14 Collection of specimens.. 14 il ePort of test results 15 Repeat wits forpresumptive positives 15 Criteria for diagnosis of PKU. "'15 Acceptable screening procedures 16 '. Evaluation 16 Part III. :Tests for OtherDisorders. 17 A.Dried blood on filter paper collected in ' ... the first week of life 18 13' Dried blood on filter ,paper collected ' I from the beginning of the,secondto the fourth week of lifi 18 , C.Cord blliod 19 D.Urine collected between,2 and 4_weeks , of age 20 Refer(oces, , 21 $ I it Foreword . In1966 the Department of Heald, Education, and Welfareissued "Recommended Guidelinesfor PKU PrograMsfor Ne----.1Iewborn" assist health departments and others in establishing screening servicesfor the detection and care of newborn infants with phenylketonuria.Programs that now function in most States were initially based onthese guidelines, and have been frequently modifi to include new developments. Butthere are problems that mtistbe addressed, particularly .in light of new possibili- ties: 1. PKU screeninw often of less than optimal ( and attainable) effectiveness. 2.P-arents are °Tier' poorly informed about screening and about the use of specimens and results. 3.Nedifital screening tests for other conditions are available but the ques- tion arises of 'when they should be used on a population-wide basis. .194. The first part of this monograph is a review of new developmentsrelated to these areas. Recommendations are presented .inthe second part. Part III provides additional -information about specific. conditions other thanPKU `that are detectable by screening . This publication is intended prirriarily for thrle involved in the organiza- tion and regulation or screening as a serviceAs the object4ve "is to find affected subjects ata time when 4ntervention may preventtheilleff of the disease" ', responsibility includessStiring that efficacious Therapy I be effectively providedProcedures inv lvedin the actualdiagnosis and management of phenylketonuria, which v.II be of Aterest to those providing care to infants with pfetimptive positive screeniitests. are dealt with in other publications 2' " The Collaborative Study, of Children ,Treated forhenylketonuria (a joint effort. of 15clinical programs coordinated througChildteri's Hospital of Los Angeles and supported by the Bureau of Co unity Health $ervices through fonds appropriated under tale V of the Sial Security Act) has collected a' great -deal of data on outcome of treatme of PKU as well as . on screening. The author'sevaluatio'n 'of screening psi,)grams was ihiMated on behalf of the CollaborativeNojeCt. V .6 , Participants in the PKU Col labor tive Project include Children's Hospital Universityof Maryland School of Los Angeles, california Medicine ,1., Baltimore, Maryland d ItegiOrtial CenteI4or the . Developmental Disabled Johns Hopl:ms'Hospital Childrens Hospital,and Health Ba1 ltimore, Maryland Center - San Diego, California Children's RetiabilitationCenter - . Childreri's Hospital University of ColoradoSchool. of Buffalo, New York - Meilicine Denver, Colorado I State University of New York - Syracuse, New York .. Mailman Centir University of Mrami Children's bitedical Center °Miami,'Florida' Tulsa, Oklahoma Co Ok CeuntY Hospital University of Texas Medical School, Chicago, Illinois Galveston, texas Children s Memorial Hospital University of Washington Chicago, Illinois Seaikt Washington Child Development Clinic 'Waismai\ Center on Mental Re- Univer4 of lovra .tardation and Human Develop- Iowa City, Iowa ment University ol< Wisconsin Midison, Wisconsin a.. Part F 'New DeveloOfnent.. PHENYLKETONURIA Prognosis At There can no longer be any &tat that the early instItuuon ofa diet low in phenylalanine is efficacious in preventing retardation from Phenyl; ketonuria. The PKJ CollabOrative Project,reports that the IQ (mean I;' s. d.r at 4 years of age in 97 PKU children identified and treated as a rg:ult of neonatal screening was-92 1.5.1.4 This is much 'big''' er than in un- S ttetteaorlate-treatedphenylketonurics,includingsibling's ofthe study group. ,The best outcome was observed in those in whom_ the diet ryas started by 3 or 4 weeks of 'age Since screening has become w,idespreld, the admission of children with PKIJ to menial institutions has yirtually ceascd. Transient 'elevations and variants No all infants who have eleva'tions ofserum phenylalanine on screening have classical PKU. Eighty-five percent of infants_ withpreAtmptive positive Igreening test results have normalconcentrations on the neW follOwup. Only 5 percent will eventually be proved -to have PKU ' Most of the remainderk with initial elevations will eventually haTe normal phenylalanineconcentra-, titans(less than 6 mg/100 `m1),but between- 1 and 2 percent will have persistent moderate elevations of. up to 20 mg/100 nil cif blood phenylalanine on regular dietsThese variants probably repi-esent several different defects '- butmost of them are not at risk of retardation " 1" Restriction of dietary _ - phenylalanine in a variant may resultin a severe' deficiency state and has , no proven benefit. Thus, in any infant with a positive screening test,*criteilia: compatible with a diagnosis of classical PKU must bc,present before therapy ai is scatted;. ' A form of phenylketckatria causing sever( retardation whichis unresponsive . , to dietary restriction of phenylalanine'has recencly been reported " In some these infants the phenylalanine concentration may notrise excessively when they are7challenged with a regular diet " This forna can be 'detected in fibroblasts and, as these infants may benefit from early treiiment with other rt es of therapy, skin biops.y for,culture should be considered in any, rnfapt with persistent elevations of phenylalanine' 7 . False negatives Between 5 and 10 percent of infants ultimately+,ptovecj
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