Newborn Screening in Saskatchewan - Information for Health Care

Newborn Screening in Saskatchewan Information for Health Care Providers

Resources

For more information on Saskatchewan’s newborn screening and the conditions screened for by the test, please visit www.health.gov.sk.ca/newborn-testing, or contact the Saskatchewan Disease Control Laboratory at (306) 787-3142 or (306) 787-7900.

Saskatchewan Disease Control Laboratory Saskatchewan Ministry of HealthLloyd Place 3211 Albert StreetRegina, SaskatchewanS4S 5W6

New address in the fall 2009

Other resources

• AmericanAcademyofPediatrics: www.aap.org/healthtopics/newbornscreening.cfm

• OrphaNet(informationaboutraredisorders): www.orpha.net

• NationalOrganizationforRareDisorders(NORD): www.rarediseases.org/search/rdblist.html

UsedandadaptedwithpermissionfromtheGovernmentofOntario.

June/09

Newborn screening: a healthy start leads to a healthier life

Since the mid-1960s, health care providers have offerednewbornscreeningforphenylketonuria(PKU)to all infants born in Saskatchewan. Today, newborn screeninghasexpandedtoscreenforatleast30plusmetabolicandendocrinedisorders.Individually,thesedisordersarerare,butwill,asagroup,affecteightto10outof13,000newbornsintheprovinceeachyear.

The Saskatchewan Disease Control Laboratory in Reginaconductsalltestingforcongenitaldisorders.

Early detection. Early treatment.

Big benefits.

Thesebabiesappearnormalatbirthand,unlesstheyarescreened,mightotherwisenotbeidentifiedtohaveone ofthesedisordersuntilirreversibledamagehasoccurred.Ifnottreated,theseconditionsareassociatedwithrecurrentillnessesand/ordevelopmentaldisabilities and/or death. Early diagnosis and treatment canresultinsignificantlyimprovedorpositiveoutcomes.Insome,preventivecarecanimproveormaintainthequalityoflifeofthesebabies.Forbabieswho start to become ill soon after birth, newborn screeningmaysavevaluabletimeandresourcesinmakingadefinitediagnosis.

Informed parents make smart choices

It’simportantthatyou,asahealthcareprovider,emphasizetoparentsthatnewbornscreeningispart oftheirbaby’sroutinecareandcouldsavetheirbaby’slifeand/orpreventserioushealthproblems.Thevastmajority of parents agree to have their baby screened. Shouldaparentrefusenewbornscreening,thedecisionshouldbedocumentedinthebaby’smedicalrecordsandtheparentswillberequiredtosignarefusalform.

What health care providers need to do

Anewbornscreeningspecimencardshouldbecompletedbetweenoneday(24hours)andsevendaysafterthebirthoftheinfant:ideally,betweentwodays

(48hours)andthreedays(72hours)afterbirth.Iftestedbefore24hoursofage,thebaby’shealthcareprovidershouldrepeatthetestwithinfivedays,atthefirstpostnatalcheck-up.

Bloodspotsfrominfantsarecollectedusingtheheel-prick method, which is detailed on the back of the specimencard.Ifyouareprovidingcareforaninfantwhoispremature(i.e.lessthan37weeksgestation),ill,hasbeentransfused,orhasbeenontotalparenteralnutrition(TPN)orantibiotics,pleaserefertotheSpecialConsiderations section on the next page.

Submitting cards: time is critical

It is critical that the Saskatchewan Disease Control Laboratory receives the newborn screening specimen card as soon as possible after the blood spots are collected.Therefore,thecardsshouldbesentnolaterthan24hoursaftercollectionand,ideally,assoonas thebloodspotsaredry(fourtosixhoursaftercollection). Babies with some of the conditions screened willstarttobecomeillandmaysufferirreversibledamage soon after birth. Rapid diagnosis and treatment can prevent this damage.

Screening test results: positive and negative

OncetheSaskatchewanDiseaseControlLaboratory hasreceivedandanalyzedthespecimencard,one ofthefollowingwilloccur:

NegativeTheinfantunderyourcare“screensnegative”forallconditions.Areportisissuedbymailtoboththereferringhospitalandshouldbefiledinthebaby’smedical records.

Repeat SampleIftheinitialsampleisinsufficientorunacceptable,or iftheresultsareequivocal,youwillbecontactedandasked to obtain another sample from the newborn as soonaspossibleandrepeatthesubmissionprocedure.

PositiveTheinfantunderyourcare“screenspositive”fora disorder. A screen positive does not necessarily meanthatthebabyhasadisorder,butthatitneedsfurtherinvestigation.TheSaskatchewanDiseaseControlLaboratorywillimmediatelynotifyyour

• A repeat sample is sometimes required

Itmaybethatthefirstsamplewasnottakenproperly, theamountofbloodtakenwasnotenoughtocomplete the testing, or there was some other problem with the sample.Ifrequested,arepeatbloodsampleshouldbe taken as soon as possible. • Discuss the difference between a screening test and a diagnostic test

A screening test determines if there is a high or low risk thatababyhasaparticularcondition.Onlyasubsequentdiagnostic test will determine with certainty if the baby is affected with a condition or not.

• Discuss possible results of screening

The baby screens negative for all disorders. A report isissuedbymailtothehealthcareprovider/referringhospital.Over99percentofbabieswhohavethenewbornscreenwillhaveanegativeresult.

The baby screens positive for one of the disorders. A screen positive does not necessarily mean that thebabyhastheconditionbutonlythatfurtherinvestigationisrequired.TheSaskatchewanDiseaseControl Laboratory will contact the Metabolic Clinic inSaskatoon,whichwill,inturn,immediatelynotifythebaby’shealthcareproviderorparentsaboutthescreenpositiveresultandarrangeforconfirmatorytesting.Ifadiagnosisofaconditionisconfirmed, theclinicwillprovidemanagementcounselling andfollow-up.

regional treatment centre (the Metabolic Clinic in Saskatoon) aboutthescreenpositiveresultandtheclinicwillarrangewithyouortheinfant’sparent(s)forconfirmatorytesting.Ifadiagnosisofadisorderisconfirmed,theclinicwillprovidemanagement,counsellingandfollow-up.Areportisalsoissuedbymail to the referring hospital and health care provider, andshouldbefiledinthebaby’smedicalrecords.

The screening test: there are limitationsIt’s important to remember that, as with all screening tests, there will be false positive and false negative results.Falsepositiveswillincreaseparentalanxiety,while false negatives will give a misleading sense ofreassurance.Ifababyinyourcareexhibitssymptomsofaparticulardisorder,butthenewbornscreenwasnegative,thechildshouldbeinvestigatedandmanagedappropriatelyandtherelevantconsultantspecialistshouldbecontactedimmediatelyforfurtheradvice.

There is wide clinical variation in some of the disorders that the newborn screen detects. Therefore, there will

beso-called“affected”individuals—babieswhoareconfirmedbydiagnostictestingtohaveaparticulardisorder—whowillremainasymptomaticevenwithouttreatment or will only have very mild symptoms.

Special considerations

Prematurity or illnessInfantswhoarepremature(i.e.lessthan37weeksgestation)orwhoaresickshouldhavetheirfirstspecimen collected for newborn screening when they arefivetosevendaysold.Prematureinfantswilloftenhaveahighthyroid-stimulatinghormone(TSH)leveland may screen positive for congenital hypothyroidism. However,onrepeatspecimens,resultscanbedifferentiatedintofalseandtruepositives.Prematurityorillnessinaninfantbeingscreenedshouldbeclearlyindicated on the newborn screening specimen card.

Total Parenteral Nutrition (TPN) and antibioticsThe Saskatchewan Disease Control Laboratory can analyzeheel-prickbloodspotsfrominfantswhohavehad TPN (hyperalimentation) or antibiotics. However, levels of certain amino acids and organic acids can be elevatedintheseinfants.Inordertoensurethemostaccurateanalysis,theadministrationofthesetherapiesshouldbeclearlyindicatedonthenewbornscreeningspecimen card. For additional information on newborn screening, visit www.health.gov.sk.ca/newborn-testing.

TransfusionsInfants who are affected with one of the disorders screened for by the Saskatchewan Disease Control Laboratory may be missed if they have had a recent bloodtransfusion.Normallevelsofnewbornscreeninganalytesmaybefoundinthesecasesbecause ofthedonorblood.Ideally,aspecimencardshould becompletedbeforetransfusion.

Disorders Screened

Organic Acid Disorders OrganicAcidemias(OA)areaclassofinheritedmetabolicdisordersthatoccurwhenthebodycannotmetabolizecertainaminoacidsandfats.Thisleadstoanaccumulationoforganicacidsinthebloodandurine,whichcancauseserioushealthproblems.ClinicalsymptomsofOAmayincludeacuteencephalopathy,

Discussion Guide

This discussion guide will help you to counsel your patients and answer their questions about newborn screening. The brochure Newborn Screening: A healthy start leads to a healthier life is also available to provide to your patient.

Health care providers offer newborn screening to all infantsborninSaskatchewan.Althoughscreeningforphenylketonuria(PKU)andcongenitalhypothyroidism(CH) have been offered in Saskatchewan since 1965 and 1978, respectively, newborn screening expanded to cover30plusdisorders.

Newborn screening is a strongly recommended part of neonatal care since babies affected with these disorders usually appear normal at birth. Unless they undergo screening, they may not be identified as

having a disorder until irreversible damage has occurred.

In many cases, preventive care can improve or maintain thequalityoflifeofthesebabiesandtheirfamilies.Forbabies who start to become ill soon after birth, newborn screeningmaysavevaluabletimeandresourcesinmakingadefinitediagnosis.Theseconditions,ifnottreated,areassociatedwithrecurrentillnessesand/ordevelopmental disabilities and/or death. Early diagnosis andtreatmentcanresultinanormaloutcome.That’swhyit’ssoimportanttodiscussnewbornscreeningwithyourpatients.

Points to discuss with expectant parents

• Offer newborn screening

Newborn screening is strongly recommended for all babies born in Saskatchewan as part of neonatal care. Resultsareveryaccurateandcover30plusdifferentconditions. These are disorders of metabolism and the endocrine system.

• Discuss the benefits of testing

Identifyingababywithoneofthedisordersisbeneficialbecauseearlydiagnosisandtreatmentcanpreventconsequencessuchasrecurrentillnessesand/ordevelopmental disabilities and/or death.

• Discuss how testing is done

The blood sample is obtained by pricking the baby’s heel. The blood is transferred to a special paper card and sent to the Saskatchewan Disease Control Laboratory.

• Testing must be timely

Acceptable samples can be taken between one day (24 hours)andsevendaysafterbirth,althoughthebesttime to collect the blood sample is when the baby is betweentwodays(48hours)andthreedays(72hours)old.Ifababyistestedbeforeoneday(24hours)ofage,thetestshouldberepeatedwithinfivedays,atthefirstpostnatalcheck-up.

Babies with some of the disorders screened will start tobecomeillandmaysufferirreversibledamagerightfrom birth. Rapid diagnosis and treatment can prevent this damage.

Examples:

Phenylketonuria (PKU) is a condition in which individualscannotusephenylalanineproperlysoitbuildsupintheblood(hyperphenylalaninemia).Withouttreatment,phenylalanineaccumulationwillcausesevereandirreversibledevelopmentaldisabilities,eczema,andotherproblems.SaskatchewanhasscreenedforPKUsince1965.

Tyrosinemia (TYR)occurswhentyrosinecannotbeproperlymetabolized,leadingtoanaccumulationofthisamino acid and its metabolites in the liver, kidneys, andthecentralnervoussystem,causingliverdisease and other problems.

Homocystinuria (HCY)occurswhenhomocystineaccumulatesintheurine.Itiscausedmostcommonly byadeficiencyinanenzymecalledcystathioninebeta-synthase (CBS). Affected babies can have developmentaldisabilitiesandfailuretothrive.Theymay also develop eye problems, skeletal problems, and a high chance of developing blood clots.

Citrullinemia (CIT) and argininosuccinic acidemia (ASA) areureacycledefects.Theureacycleis the body’s system for excreting waste nitrogen and ammonia,andforsynthesizingarginineandurea.Hyperammonemiaresultswhenoneoftheenzymesintheureacyclefunctionsimproperly.Symptomscanincludelethargy,vomiting,coma,seizures,liverdisease,failuretothrive,anddeath.

Maple syrup urine disease (MSUD) occurswhentheaminoacids,leucine,isoleucine,andvalinecannotbemetabolized.Symptomsincludepoorfeeding,lethargy,convulsions,andevendeath.Theurineofanaffectedchildcanhavetheodourofburntsugarormaplesyrup,giving the disorder its name.

Other Disorders Congenital hypothyroidism (CH) cancausedevelopmentaldisabilitiesandfailuretothriveifnotrecognizedandtreated.Itisarelativelycommonconditionandistheresultofathyroidhormonedeficiency.SaskatchewanhasscreenedforCHbymeasuringthyroidstimulatinghormone(TSH)levels in blood since 1978. Thyroid hormone replacement is a very effective treatment.

Congenital adrenal hyperplasia (CAH) is an inherited defect in which the adrenal gland cannot make cortisol andoverproducesmalehormones.Withoutcortisol,infantsmaybeunabletoregulatesaltandfluids, and can die. Some newborns with CAH can be symptomaticatbirthwithvirilizationoffemales.Replacementofdeficienthormonesisaneffectivemeans of preventing a salt-wasting crisis and preventing long-term complications.

Biotinidase deficiency (BIOT) - Biotinidase is essential for the recycling of the vitamin biotin, which, inturn,isanenzymecofactor.Theseenzymes,thecarboxylases,areimportantintheproductionofcertainfats and carbohydrates and for the breakdown of proteins.Featuresofthisdisorderincludeneurologicalsymptoms,suchasdevelopmentaldisabilitiesandseizures,andcutaneoussymptoms,suchashairloss and skin rash, which can be effectively treated with biotinsupplementation.

Cystic fibrosis (CF) is an inherited disease that affects thelungsanddigestivesystem.Thebodyproducesthickmucusthatmayinterferewithlungfunctionand/ordigestion. Approximately one in 3600 children born in Canada has CF.

Galactosemia (GALT)—Lactoseisthemainsugarinbreastmilk,cow’smilk,andmanyinfantformulas.Thissugarismetabolizedintoglucoseandgalactoseintheintestine.Individualswithgalactosemiaarenotabletobreakdowngalactose.Thiscanresultinlife-threateningcomplicationsincludingfeedingproblems,failuretothrive,liverdamage,bleeding,andsepsisinuntreatedinfants.Adietrestrictedinlactoseisveryeffective in preventing these complications. Even with early treatment, however, children with galactosemia are at increased risk for developmental disabilities, speech problems,abnormalitiesofmotorfunctionsand,infemales,prematureovarianfailure.

Please note: The disorders for which the Saskatchewan Disease Control Laboratory screens may change over time. For the most current list, please check the Saskatchewan Disease Control website at www.health.gov.sk.ca/lab

vomiting, metabolic acidosis, ketosis, dehydration or coma, hyperammonemia, lactic acidosis, hypoglycemia, failuretothrive,hypotonia,globaldevelopmentaldelay,sepsis, hematological disorders, and death. Newborns withOAsareperfectlyhealthyatbirth,butmaybecomequiteillwithinthefirstfewdaysoflife,evenbeforetheresultsofthenewbornscreeningareknown.Treatmentoften involves a low-protein diet and/or a diet low inspecificaminoacidsand/ordietarysupplements(suchascarnitine,biotin,riboflavin),medicalfoodsor other medications. It is very important for affected individualstoavoidfasting.IncludedintheOAsforwhich Saskatchewan screens are isovaleric acidemia (IVA),glutaricacidemiatype1(GA1),HMG-CoAlyasedeficiency(HMG),multiplecarboxylasedeficiency(MCD), methylmalonic acidemia, 3-Methylcrotonyl-CoAcarboxylase(MCC)deficiency,propionicacidemia(PROP),B-Ketothiolase(BKT)deficiency,anddienoylCoAreductasedeficiency.

Fatty Acid Oxidation Defects (FAODs) The breakdown of fatty acids in the mitochondria isanessentialpartofthebody’sabilitytoproduceenergy, especially if an infant has nothing to eat for morethanafewhours,forinstance,duringillness.Fatty acids are transported into the cell and then into themitochondria.Onceinthemitochondria,thecarbonchainsorfattyacidsaremetabolizedtwoatatime,usingspecificenzymes.Ifthetransportermolecule(s)oranyoftheenzymesusedtoreducethenumberof

carbonsinthechainaremissing,anaccumulationoffattyacidsinthebodyoccursandcauseshypoketotichypoglycemiaandtissuedamage,especiallyliver,muscle,andheartdisease.Lethargy,seizures,coma, andsuddendeatharealsosignsofFAODs.AnundiagnosedFAODcanpresentassuddeninfantdeathsyndrome(SIDS).Dietarysupplementationwithcarnitine and/or cornstarch may also be part of the treatmentforFAODs.Itisveryimportantforaffectedindividualstoavoidfasting.

IncludedintheFAODsforwhichSaskatchewan screensaremediumchainandshortchain acyl-CoA dehydrogenase (MCAD) and SCAD deficiency,verylongchainacyl-CoAdehydrogenase(VLCAD)deficiency,longchain3-Hydroxyacyl-CoAdehydrogenase(LCHAD)deficiency,trifunctionalprotein(TFP)deficiency,andcarnitineuptake defect (CUD).

Amino Acid Disorders Thesedisordersoccurwhenthebodycannoteithermetabolizeorproducecertainaminoacids,resulting inthetoxicaccumulationofsomesubstancesandthedeficiencyofothersubstances.Aminoacidsarederivedfrom protein. Treatment often involves a low-protein dietand/oradietlowinspecificaminoacids.Specificmedications and/or vitamins may also be prescribed, depending on the disorder. It is very important for affectedindividualstoavoidfasting.