2017 ANNUALREPORT

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Spotlight

Overview

Research

OurVisionAging,dietorhereditarypredispositionareamongthefactorsthatmaymakeitmoredifficulttoabsorbanessentialvitaminandcofactorfornucleicacidsynthesisi.e.,vitaminB12.Thiscobalt-containingclassoforganiccompoundsisproducednaturallybybacteria,whilehumansobtainB12fromanimalproductsorfortifiedfood.OneofthemostcommonformsofB12deficiencynotedinprimaryhealthcareistheautoimmunecondition,perniciousanemia(PA).OneormorebloodtestsmayreveallowserumB12levelsorcellsmaynotbeabletotakeupB12,evenwhenserumlevelsarewithinreferenceranges.WewishtoraiseawarenessaboutPAandotherB12malabsorptionsyndromesbydisseminationofpreclinicalandclinicaloutcomestopatientsandtheirhealthcareproviders.

Spotlight

ReflectingonBloodTestsSelectedstudieshaveusedaB12cut-offof<350pg/mLtoestimatetherangeofpeopleatriskorwithvitaminB12deficiencies.However,todate,thereisnogoldstandardforthemeasurementofB12deficiency.Lab-to-labandcountry-to-countryvariationsexistintermsofreferencevaluesanddiagnosis.Coexistentmedicalconditionscanalsolimituse.Wesuggesttheuseofmorerobusttestsandreferencestandardstobeusedasadjunctsinscreeningat-riskpopulations.

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70

39

5

25

USA(olderadults)

Developingworld

AtriskintheUSA

Ranges(%)ofPersonsSuspected/IdentifiedwithB12Deficiencies

TypicalLifelongTreatment:IntramuscularInjection

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OverviewPA–anautoimmunediseasetriggeredbymanyfactors–ischaracterizedbyvitaminB12deficiencyduetomalabsorptionoftheessentialmicronutrientfromtheterminalileum,autoimmunechronicatrophicgastritis,andthepresenceofintrinsicfactorandparietalcellantibodies.Accordingtoexperts,timelydiagnosisusingacombinationoftestsisimportanttoforestalldireconsequencese.g.,hematologic,cardiovascular,andneurologicalcomplications.

PerniciousAnemia

Infact,higherlevelsofbothMMAandHCwerefoundtobe~100%predictiveoffunctionalB12deficiency.However,doctorsstillhavetobesleuthsinidentifyingandmanagingPA,becauseofthediverseclinicalpresentationsofthediseaseandthelimitedtoolsintheirkits.Someofthedilemmasdiscussedina2017DiscoveryMedicinepaperbyOoandcolleagues,includeidentifyingpatientswithPAinthepresenceof"spuriouslynormalorhighcobalaminlevels,normocyticormicrocyticanemia,non-anemicmacrocytosis,autoimmunehemolyticanemia,pseudo-thromboticmicroangiopathy,hyperhomocysteinemia-associatedthromboembolism,pseudo-leukemia,bonemarrowfailure,bonemarrowringsideroblasts,andneurologicmanifestationswithoutanemiaormacrocytosis."

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Serumbuild-upofMethylmalonicAcid(MMA)causedbyB12deficiency.

DeficiencyofvitaminB12orfolicacidcanleadtoincreasedhomocysteine(HC)levels.

"Screeningmaybewarrantedinpatientswithoneormoreriskfactors,suchasgastricorsmallintestineresections,inflammatoryboweldisease,useofmetforminformorethanfourmonths,useofprotonpumpinhibitorsorhistamineH2blockersformorethan12months,vegansorstrictvegetarians,andadultsolderthan75years."(Langanetal.,2017)

Research

RecentEvidenceInher2013NEJMarticle,Dr.StablerdescribesB12deficiencyascausing"reversiblemegaloblasticanemia,demyelinatingdisease,orboth."Thisconditionhasbeentreatedwithhigh-doseoraltherapyoraB12injection.Basedon2randomizedcontrolledtrials,3prospectivepapers,1systematicreview,and3clinicalreviews,reflectingresearchovermorethan2decades,otherauthorshavesuggestedthathigh-doseoralB12therapywasaviablealternativetointramuscularinjectionsforthetreatmentofPA.

ThreecommercialformulationsofB12arecurrentlyavailable(cyanocobalamin,hydroxocobalamin,andmethylcobalamin).ConcernshavebeenraisedregardingoraladministrationofB12topatientswitharangeofcomplications,includingrenalimpairmentandneurologicabnormalities.Injectionsinthesecasesaresuggestedaspreferredoptions.Currently,aPhase4studyisunderwaytoassessthesafetyofamegadoseofhydroxocobalaminforthetreatmentofPA(lastclinicaltrials.govupdateposted:December13,2017).

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SystematicReview/TrialofB12forPATreatment

1980to2016 2017

Meta-Analysis Phase4study(NCT03372447)0

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Sources:SeeSlideShare