Rev. Bras. Hematol. Hemoter. vol.38 número3

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rev bras hematol hemoter. 2016;38(3):190–192

w w w . r b h h . o r g

Revista

Brasileira

de

Hematologia

e

Hemoterapia

Brazilian

Journal

of

Hematology

and

Hemotherapy

Scientific

Comment

Comments

on:

“Clinical,

hematological

and

genetic

data

of

a

cohort

of

children

with

hemoglobin

SD”

夽

Maria

Stella

Figueiredo

∗

UniversidadeFederaldeSãoPaulo(UNIFESP),SãoPaulo,SP,Brazil

Sickle cell disease (SCD) is a group of genetic conditions relatedtothepresenceofasicklehemoglobin(HbS) muta-tion(HBB:c.20A>T).PeoplewithSCDcanbehomozygousfor Hb S or can havecompound heterozygosity for Hb S with othergenemutations.1,2_Some_hematologic_features_of_SCD arelisted inTable1, butraregenotypes canalsobefound. SincetheconcentrationofHbSisapathophysiologicalfactor ofdisease severity,thepresenceoflower concentrationsof HbSduetodoubleheterozygositycandeterminephenotypic heterogeneity.1,3 _However,_other _genetic_and _{environmental} factorscanalsohaveaneffectonthediseasephenotype.4

Studies looking for abnormal hemoglobins (Hbs) in the Brazilianpopulationhavebeenperformedsincethe1950s.5–8 However, the Brazilian Government Directive MS # 822/01 that regulates newborn screening for hemoglobinopathies, haspromotedanincreaseofdataabouthemoglobinopathies indifferentBrazilianregions.9–11_This_associated_with_the_use ofisoelectricfocusingelectrophoresis(IEF)andhigh-pressure liquid chromatography (HPLC) as diagnostic methods, has enabledtheidentificationofanincreasingnumberof abnor-malHbsaswellascompoundheterozygousstatesofHbS.12–14 AnexampleisapaperpublishedinthisissueoftheRevista BrasileiradeHematologiaeHemoterapiathatshowsdataon acohortofchildrenwithhemoglobinSDpattern.15

Hb D is an abnormal Hb, which migrates to the same

positionasHbSinelectrophoresisatalkalinepH,andcan beseparated fromHb S inacidpH.16–18 _Several_Hb _D _have been described in different racial groups, but the majority presented a point mutation in codon 121 of the ␤-globin gene,whichresultsinthesubstitutionofglutamicacid for

DOIoforiginalarticle:http://dx.doi.org/10.1016/j.bjhh.2016.05.002.

夽

SeepaperbyRezendeetal.onpages240–6.

∗ _{Corresponding}_author_at_:_Departamento_de_Oncologia_Clínica_e_{Experimental,}_Disciplina_de_Hematologia_e_Hemoterapia,_Universidade

FederaldeSãoPaulo(UNIFESP),RuaDrDiogodeFaria,824,3◦_andar,_Vila_Clementino,_04037-002_São_Paulo,_SP,_Brazil. E-mailaddress:stella.figueiredo@unifesp.br

glutamine(HBB:c.364G>C).ThisabnormalHbisusuallycalled Hb D-Punjab or Hb D-Los Angeles, howeverit can alsobe namedHbD-NorthCarolina,HbD-Chicago,HbD-Portugal,Hb D-Cyprus,andHbD-OakRidge.19–21_The_estimated_prevalence ofHbD-Punjabis0.1to0.4%inAfrican-Americans.22_In_Brazil, astudyofAfricandescendantsshowedasimilarprevalence.5 SometimeafterthediscoveryofHbD-Punjab,the coinher-itanceofHbD-PunjabandHbSwasidentifiedinCaucasian patientswithclinicalandhematologicalmanifestations simi-lartothoseofsicklecellanemia(SCA),becausethismutation facilitatesHb Spolymerization.23–25 _Further_clinical _studies confirmedthe severityofthemanifestationsofthis associ-ationandtheneedtotreattheseindividualsasSCApatients byprescribinghydroxyureawhenindicated.21,26–29

ThereareothertypesofHbDduetodifferentpoint muta-tionsinthe␤-globingene,suchasHbD-Iran(HBB:c.67G>C) andHbD-Ibadan(HBB:c.263C>A).However,individualswith thesemutationshavenormalhematologicvaluesanddonot sufferfromvaso-occlusivecomplications,sincetheirredcells donotsickleunderphysiologicconditions.18,30,31

HbKorle-Bu(HbKB)orHbG-Accra(HBB:c.220G>A)isa fre-quentmutationinSub-SaharanAfrica.32,33 _This_Hb_has_the same IEFmobilityasHbD-Punjabbutcanbedifferentiated byHPLC.HeterozygotesforHbKBhavenohematologic alter-ations,andindividualswithdoubleheterozygosisHbS-HbKB havenormalredcellsonbloodsmearandabenignclinical course,similartosicklecelltraitasHbKBdoesnotparticipate inthegelationofHbS.33,34

Interestingly,the HbKBmutation[beta73(E17)Asp→Asn] canoccurinadditiontotheHbSmutation[beta6(A3)Glu6Val]

http://dx.doi.org/10.1016/j.bjhh.2016.05.012

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revbrashematolhemoter.2016;38(3):190–192

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Table1–Hematologicalfeaturesofsomesicklehemoglobinopathies.

Genotype PCV(%) Retic(%) MCV(fL) HbF(%) HbA2(%) %Variant Severitya

SCA 25 8 90 5 3 >90%HbS ++++

HbSCdisease 35 3 80 2 3 50%HbS,50%HbC ++

S-␤0_thalassemia ₂₇ ₇ ₈₂ ₇ ₅ _90%_Hb_S ₊₊₊₊

S-␤+_thalassemia ₃₈ ₂ ₇₀ ₂ ₆ _5–30%_Hb_A ₊₊

SCA-␣thalassemia 30 6 78 5 5 >90%HbS +++

HbSEdisease 35 3 75 2 3 ∼30%HbE ++

HbSDdisease* 20 86 1–10 2–4 45%HbS,45%HbD +++

Sicklecelltrait 45 1 85 1 2 60%HbA,40%HbS

SCA:sicklecellanemia;PCV:packedcellvolume;Retic:reticulocytecount;MCV:meancellvolume;Hb:Hemoglobin.

a _Severity_of_disease_rated_from_most_severe₍₊₊₊₊₎_to_absence_of_clinical_events₍ ₎_includes_{complications}_related_to_sickle_{vaso-occlusion}_and

hemolysis.

Tablemodifiedfrom1with*dataobtainedfrom21,27,32.

inthesamebetaglobinchain.Inthiscase,thisHbwitha dou-blemutationistermedHbC-Harlem(orHb C-Georgetown) (HBB:c.20A>T,HBB:c.220G>A),becauseitmigratestothe posi-tionofHbCincelluloseacetateelectrophoresisatalkalinepH. IndividualsheterozygousforHbC-Harlemareasymptomatic, butthecoinheritanceofHbSandHbC-Harlemhasclinical manifestationssimilartoSCA.20,32,35

ResearchersfromIndiaandtheMiddleEastarethemain authorsofthefewpapersaboutHbSD-Punjab;thereareless datapublishedabouttheassociationHbS-HbKB.21,27–29,34,36–41 BystudyingtwodifferentgroupsofpatientswithHbSD pat-terns,specificallyHbSD-PunjabandHbS-HbKB,Rezendeetal. notonlypublishedimportantclinicaldataaboutthe coinher-itanceoftworareHbbutalsopointedouttheimportanceof thisdifferentialdiagnosis.15

Conflicts

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Theauthordeclaresnoconflictsofinterest.

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