3 microcytic anemia ii-thalassemia trait.ppt

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Information about 3 microcytic anemia ii-thalassemia trait.ppt

Published on September 26, 2018

Author: AbdulKaderSouid

Source: slideshare.net

1. Microcytic Anemia II Microcytosis (↓MCV) = Impaired (↓) Hemoglobin Synthesis Abdul-Kader Souid9/26/2018 (1) Iron deficiency anemia; (2) Thalassemia trait; (3) Inflammation; (4) Sideroblastic anemia Target cells in thalassemia trait The quaternary structure of hemoglobin consists of 2α (red) & 2β (blue) subunits, each has iron-containing heme (green) that binds O2. Five important points Synthesis of the a globin peaks prenatally. The b globin peaks at 3 mo of age. Thus, a-thalassemia manifests at birth (cord blood MCV <94 fL) and b-thalassemia manifests after 3 mo of age. Target cells have ↑cell membrane (↑cell surface)

2. 2     b 3’5’     b 3’5’ Chromosomes 11 (two alleles)  a2 a1 3’5’ Chromosomes 16 (two alleles)  a2 a1 3’5’ Normal Hemoglobin Variants The four globins (a, b, , ) form three normal hemoglobin variants: A (>93%) = 2a + 2b A2 (<3.5%) = 2a + 2 (↑ in b-thalassemia trait) F (<3.5%) = 2a + 2 (↑ in b-thalassemia trait) Must know (5 points) Tetramers of “” or “b“ are abnormal variants and indicate a-thalassemia. Hemoglobin Barts = 4 (newborn) Hemoglobin H = 4b (≥1 y of age)

3. a-Thalassemia Trait  a2 a1 3’5’ Chromosomes 16 (two alleles)  a2 a1 3’5’ When there is production of the α gene on a chromosome 16 (only one of the two α genes on a chromosome is deleted; trans deletion; (-,a/-,a), the designation for that chromosome is α+ thalassemia (α+). When both α genes on a single chromosome 16 are deleted (cis deletion; (-,-/a,a) ), the designation α° (null allele) is used for that chromosome. Must know (2 points) α° thalassemia (α°) is prevalent in China, Thailand, Malaysia, and Philippines (Asian & Mediterranean). α+ thalassemia (α+) is benign and common in the UAE, occurring in >20% of the population

4. b-Thalassemia Trait     b 3’5’     b 3’5’ Chromosomes 11 (two alleles) One b-globin gene mutation (heterozygous bo or b+; only one abnormal allele) → b-thalassemia trait → mild anemia, ↓MCV, ↑RBC count + normal RDW + ↑A2 (2a, 2) >3.5%. Two b-globin gene mutations (homozygous bo or b+; two abnormal alleles) → b-thalassemia major → severe anemia (transfusion dependent after 3 mo of age). Must know (2 point)

5. Thalassemia Trait: Summary • The term “thalassemia” refers to the inherited disorders characterized by decreased (“trait”) or absent (“major”) a or b globin. • a-thalassemia trait (a deletion allele) refers to ↓ a-globin (usually gene deletion). – Biomarkers for a-thalassemia trait include: (1) Persistent microcytosis (MCV at birth <94 fL and MCV at adulthood <80 fL), (2) Hemoglobin Bart (4) at birth (2.5% to 5%) and H (4b) at adulthood, (3) Normal A2 (2a2), (4) Two a gene deletions. • b-thalassemia trait (bo or b+ allele) refers to ↓ b-globin (usually gene mutation). – OMIM#613985 – Biomarkers for b-thalassemia trait include: (1) Microcytosis after 3 mo of age, (2) ↑ hemoglobin A2 (2a2), (3) HBB (hemoglobin beta) gene mutation. 9/26/2018 5

6. This Emirati family has a-thalassemia trait • Father: Hemoglobin 127 g/L, MCV 68 fL, A = 95%, F = 2.0%, A2 = 3.0% (a-thalassemia trait). • Mother: Hemoglobin 115 g/L, MCV 72 fL, A = 95%, F = 3.0%, A2 = 2.0% (a-thalassemia trait). • Daughter (22 mo): Hemoglobin 115 g/L, MCV 61 fL, A = 96%, F = 2.0%, A2 = 2.0% (a-thalassemia trait). 9/26/2018 6 trans deletion (-,a/-,a) α+ thalassemia (α+) Frequency (f) of the silent allele (-,a) in UAE is about 50% (= 0.5). Frequency (f2) of a-thalassemia (-,a/-,a) in UAE is 25% (0.5 x 0.5 = 0.25). Must know

7. A 27-year-old woman presents with mild microcytosis, ↑A2, and normal serum ferritin Alpha-Thalassemia PCR Beta-Thalassemia PCR https://www.omim.org/ IVS1-5 (G→C) mutation is the most common β-thalassemia mutation. https://www.ncbi.nlm.nih.gov/clinvar/variation/15447/ NMD, nonsense-mediated mRNA decay; HBB gene (OMIM#141900), hemoglobin beta locus; IVS-1 5, InterVening Sequence (intron).

8. Required Reading • Harteveld CL, Higgs DR. Alpha-thalassaemia. Orphanet J Rare Dis. 2010;5:13. doi:10.1186/1750-1172-5-13. • Danckwardt S, Neu-Yilik G, Thermann R, Frede U, Hentze MW, Kulozik AE. Abnormally spliced beta-globin mRNAs: a single point mutation generates transcripts sensitive and insensitive to nonsense-mediated mRNA decay. Blood. 2002;99:1811-6. PubMed PMID: 11861299. • Kukreti R, Dash D, E VK, Chakravarty S, Das SK, De M, Talukder G. Spectrum of beta-thalassemia mutations and their association with allelic sequence polymorphisms at the beta-globin gene cluster in an Eastern Indian population. Am J Hematol. 2002;70:269-77. PubMed PMID: 12210807. 9/26/2018 8

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