Sickle Cell Anemia

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Retrieved

2021-01-23

Source

Orphanet

Trials

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Genes

HBB, NFE2L2, HP, TNF, VCAM1, DHODH, NPPB, CAD, CACNA1C, UMPS, HMOX1, SPTA1, BCL11A, HBG2, UGT1A8, HBE1, UGT1A10, UGT1A4, UGT1A7, UGT1A6, UGT1A3, UGT1A9, UGT1A5, G6PD, UGT1A1, ARAP1, OR51B5, UBIAD1, EDN1, MYB, OR51I2, MCC, RN7SL263P, SELP, LINC01847, PGF, MUC4, MTHFR, NPRL3, RABEP1, HBG1, CD34, HBA2, HBA1, GABPA, SORCS2, NOS3, HBS1L, F5, HPX, SCD, RHCE, ALB, SELL, VWF, APOL1, MBL2, RHD, F2, CAT, HAMP, CSF3, BCAM, VEGFA, REN, F3, EPO, HPGDS, CCR5, UGT1A, IL6, HIF1A, IL1B, CXCL8, HLA-DRB1, SCT, SELE, SERPINE1, ABO, CYP2D6, PSMA7, GSTT1, GSTK1, FUT1, KLF1, DLL3, IFNG, IGF1, CCL2, SOD2, TBX6, IL4, SLCO6A1, TRV-AAC1-4, CSF2, TGFB1, MIPEP, ANXA5, SPHK1, HLA-DQB1, ANXA1, KL, THBD, AKT1, GSTM1, PLF, HBD, MIR144, MPO, APOB, RAPGEF5, AGT, THBS1, ANGPT2, MYH9, ICAM4, LCN2, ADRA1D, CXCL10, NT5E, IL18, PDE5A, IL10, MBTPS1, ADCY6, AGER, ADRB2, IL1A, PPBP, IGFBP3, PRKAR1A, TNFRSF1A, GSTP1, GCH1, VPS51, SCD5, SAR1A, ADAMTS13, COMT, FCGR3B, RUNX2, KDM1A, ATP2A2, ANTXR1, CD14, CAPN1, HES7, DECR1, CD59, CYP2C19, RBM45, CTLA4, CD38, TFPI, CPLANE1, PRDX2, LIN28A, NOD2, CDH23, PRRT2, UGGT1, CHD7, CAMKMT, KLF10, NLRP3, GALNT13, TIE1, TK2, APOA5, TLR2, CCR2, MIR454, TNFSF15, TALDO1, TACR1, KRT88P, ROS1, RPS19, RYR1, KRT90P, LOC107987479, SCN2A, HOPX, CCL5, CCL7, CX3CL1, MPIG6B, CBSL, SFTPD, SLC12A4, SLC14A1, SLCO1A2, SMPD1, SPG7, SPRR2A, CD24, LPCAT1, SLC35A2, TRIM21, TAC1, SPTBN1, NCF1, RIPPLY2, UGT2B7, PER2, MIR326, CBX3, ZPR1, MBD2, TRPA1, RSPH1, SPIN1, HPSE, SKA2, ZFYVE9, LIPG, GRAP2, DMRT2, MIR301A, MIR214, AHSA1, KAT5, VHLL, LINC01194, GDF15, APOBEC3B, TRIM13, LPCAT3, CEBPZ, NR1I3, PIEZO1, APLN, SMUG1, DIANPH, BEAN1, KEAP1, CPVL, MESP2, TRPV1, EOS, HBFQTL2, AIMP2, CXADRP1, AKAP1, BRAP, LOH19CR1, PLA2G6, PRRX2, NANOS1, AHSP, OR10A4, ICOS, IL37, HAVCR1, TNFSF14, SLC17A5, TNFRSF6B, POLDIP2, RNF19A, CLDN15, PROZ, LRSAM1, ABCA1, MOK, CLDN3, CYBB, CXADR, CTSK, CST3, MAPK14, CRYZ, CRP, CRK, COX8A, CD40LG, COL4A1, CCR4, CLCN7, CHM, CHIT1, CTSC, CDA, CD63, CD55, ACE, CYB5R3, DNASE1, FOXO3, FKBP4, FH, FES, FDPS, FCGR3A, FCGR2A, FAAH, ETFA, EPAS1, ELAVL2, ELANE, EGR1, S1PR1, ATN1, DRD3, DRD2, CD47, CD36, FOSB, AMBP, ARG1, ABCC6, FAS, APOE, APOA1, BIRC3, BIRC2, AMH, ALOX5, CD28, ALAS2, AKT2, ADORA2B, ADCY9, ADA, ACP3, ACP5, ACHE, ARR3, ASS1, ATP2B4, AVPR1A, CD19, CD6, CD1C, CD1B, CD1A, KRIT1, CBS, CASR, CASP3, CASP1, CALM3, CALM2, CALM1, BTK, BRCA1, BDNF, BAX, FOS, MTOR, PTX3, MYH2, P2RY6, OXCT1, OLR1, OAT, NOS1, NM, NHS, NGF, MUC1, LFNG, MST1R, MFGE8, MCL1, MAP6, SMAD2, SMAD1, LYZ, LTB, P4HB, PAPPA, PER1, PF4, PTH, PRNP, MAPK8, MAPK1, PRKCB, PRKCA, PPARG, PPARA, PON3, PON1, PLXNA2, PLG, PLA2G4A, PLA2G2A, PLA2G1B, SERPINA1, ABCB1, LGALS3, LDLR, FUCA2, GYPA, HLA-G, HLA-E, HLA-A, HFE, CFH, HEXA, SERPIND1, GZMM, GTF2I, LCAT, GSR, CXCL1, NR3C1, CBLIF, GH1, GAPDH, GAD1, ACKR1, HMGB1, HMGCR, HSP90AA1, ICAM1, LAMC2, KRT12, KLRC3, KCNN4, JUND, JUNB, JUN, ITGB2, ITGAL, ITGA4, INSIG1, IMPA1, IL17A, CXCR2, IL5, IL2, IGF1R, HBB-LCR

Drugs

(S)-3'-(OH)-desazadesferrithiocin-polyether, magnesium salt, 2,2-dimethylbutyric acid, sodium salt, 4,5-dihydro-2-(2,4-dihydroxyphenyl)-4-methylthiazole-4(S)-carboxylic acid

(S)-3'-(OH)-desazadesferrithiocin-polyether, magnesium salt, 2,2-dimethylbutyric acid, sodium salt, 4,5-dihydro-2-(2,4-dihydroxyphenyl)-4-methylthiazole-4(S)-carboxylic acid, 5-hydroxymethyl-2-furfural, Allogeneic multi-virus specific T lymphocytes targeting BK virus, cytomegalovirus, human herpesvirus-6, Epstein Barr virus and adenovirus, Autologous CD34+ haematopoietic stem cells transduced with lentiviral vector encoding the human betaA-T87Q-globin gene ( ZYNTEGLO ), Autologous CD34+ hematopoietic stem cells transduced with LentiGlobin BB305 lentiviral vector encoding the human BA-T87Q-globin gene, Benserazide hydrochloride, Decitabine and tetrahydrouridine, Deferasirox ( EXJADE, DEFERASIROX MYLAN ), Deferiprone ( FERRIPROX, DEFERIPRONE LIPOMED ), Docosahexaenoic acid ethyl ester, Extract of Sorghum bicolour leaf, Pterocarpus osun stem, Piper guineense seed and Caryophylli flower, Human erythrocytes encapsulating inositol hexaphosphate, Human haptoglobin, Humanised monoclonal antibody against P-selectin ( ADAKVEO ), Hydroxycarbamide ( DROXIA, HYDREA, SIKLOS, XROMI ), L-Glutamine ( ENDARI, NUTRESTORE ), Levoglutamide, PDE9 Inhibitor, Pegylated carboxyhaemoglobin, Poloxamer 188, Rivipansel, Sevuparin, Sirolimus ( RAPAMUNE ), Synthetic hepcidin, Voxelotor ( OXBRYTA ), autologous CD34+ hematopoietic stem cells with a CRISPR-edited erythroid enhancer region of the BCL11A gene, haematopoietic stem cells and blood progenitors umbilical cord-derived expanded with (1R, 4R)-N1-(2-benzyl-7-(2-methyl-2H-tetrazol-5-yl)-9H-pyrimido[4,5-b]indol-4-yl)cyclohexane-1,4-diamine dihydrobromide dihydrate

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Sickle cell anemias are chronic hemolytic diseases that may induce three types of acute accidents: severe anemia, severe bacterial infections, and ischemic vasoocclusive accidents (VOA) caused by sickle-shaped red blood cells obstructing small blood vessels and capillaries. Many diverse complications can occur.

Epidemiology

The prevalence of sickle cell carriers in 25 European states is estimated at about 1/150. In central and western Africa (15-25%), in the French West Indies (10-15%) and in Mediterranean areas (1-15%) a high prevalence is observed in areas that are or have been affected by malaria, because the trait offers protection against pernicious malaria.

Clinical description

The presence of fetal hemoglobin means that the disease doesn't manifest until after 3 months. Clinical manifestations are extremely variable between individuals and at different times. In addition to anemia and bacterial infections, VOAs cause hyperalgic focal ischemia (and sometimes infarction) when they occur in the muscles or skeleton. Over the course of time, VOAs may compromise the integrity of tissues or organs.

Etiology

Sickle cell anemia is determined by combinations of two abnormal alleles of the beta globin gene among which at least one carries the beta 6 glu-val mutation (Hb S). Individuals who carry the gene for hemoglobin S and the gene for thalassemia beta are affected by thalassodrepanocytosis. The betaS/betaC (beta 6 glu-lys) form is also frequent.

Diagnostic methods

Diagnosis is based on analysis of hemoglobin using isoelectric focusing, by HPLC, solubility test (Itano test) and molecular analysis. Screening of healthy carriers by family or by population can be suggested and requires prospective genetic counseling.

Differential diagnosis

Differential diagnoses include other hereditary hemolytic diseases.

Antenatal diagnosis

Prenatal diagnosis is possible, after genetic counseling, by molecular analysis of a sample of chorionic villi or amniotic fluid.

Genetic counseling

Transmission is autosomal recessive.

Management and treatment

From birth, management should integrate prevention of infections, pain and eventual complications, with social and psycho-educational support, within multidisciplinary centers that are equipped with intensive care (immediate access to blood transfusion). An orphan drug based on hydroxycarbamide (hydroxyurea) has obtained European marketing authorization for the severe forms of the disease. Regular or occasional transfusions remain an essential therapeutic method. Bone marrow transplantation is indicated in cases with cerebral vasculopathy.

Prognosis

The prognosis is difficult to predict. Serious VOA or organ failure can be a cause of death.