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OTHER HEMOGLOBINOPATHIES
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More than 600 mutations in the genes encoding the α- and β-globin polypeptides have been documented. As with most mutational events, the majority of these lead to few, if any, clinical problems. There are, however, several hundred mutations that give rise to abnormal Hb and pathologic phenotypes. Hb mutants or hemoglobinopathies are usually named after the location (hospital, city, or geographical region) in which the abnormal protein was first identified. They are classified according to the type of structural change and altered function and the resulting clinical characteristics (Table 4.1 and 4.2). While many of these mutants have predictable phenotypes, there are others that are surprisingly pleiotropic in their impact on multiple properties of the Hb molecule. With few exceptions, Hb variants are inherited as autosomal recessive traits. Occasionally, double heterozygotes are identified, e.g., HbSC (see Fig. 4.8).
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Table 4-1. Classification and examples of hemoglobinopathies.
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Classification and examples of hemoglobinopathies
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ClassificationCommon name mutation Biochemical changeClinical consequences
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abnormal solubilityHbC (common)Glu6 β→Lyscellular crystallization of oxygenated protein; increased fragilitymild anemia; splenomegaly (enlarged spleen)
Body_ID: T004001.150
decreased O2 affinityHb Titusville (rare)Asp94 α→Asnheterodimer interface altered to stabilize T-statemild cyanosis (blue-purple skin coloration from deoxygenated blood)
Body_ID: T004001.200
increased O2 affinityHb Helsinki (rare)Lys82 β→Metreduced binding of 2,3-BPG in T-statemild polycythemia (increased erythrocyte count)
Body_ID: T004001.250
ferric heme (methemoglobin)HbM Boston (rare)His58 α→Tyraltered heme pocket (loss of distal His) and decreased Bohr effectcyanosis of skin and mucous membranes
Body_ID: T004001.300
unstable proteinHb Gun Hill (rare)Δβ91-95misfolding caused by loss of Leu in heme pocket and shorter helixformation of Heinz bodies (inclusions of denatured Hb); jaundice (yellow coloration of integument and sclera); pigmented urine
Body_ID: T004001.350
abnormal synthesisHb Constant Spring (rare)ter142 α→Glnloss of termination codon; decreased mRNA stabilityα-thalassemia (hemolytic anemia,splenomegaly, and jaundice)
Body_ID: T004001.400
Body_ID: T004001.450
Body_ID: T004001

Hemoglobinopathies are usually classified according to the most prominent change to the protein's structure, function, or regulation. Initial identification of a mutation often involves electrophoretic or chromatographic analysis, as shown in Figure 4.8 for HbSC, a double heterozygous genotype associated with a sickle cell disease-like phenotype.
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Table 4-2. Complete blood count.
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Complete blood count (CBC)
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ParameterSampleNormal value*
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white blood cell count,WBC6.82 ×103/mm34.5-11.0 ×103
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red cell count, RBC4.78 ×106/mm34.1-5.1 ×103 (F)
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  4.5-5.3 ×103 (M)
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hemoglobin, Hb9.9 g/dL12.0-16.0 (F)
Body_ID: T004002.300
  13.0-18.0 (M)
Body_ID: T004002.350
hematocrit, HCT33.4%36-46 (F)
Body_ID: T004002.400
  37-49 (M)
Body_ID: T004002.450
mean corpuscular volume, MCV71.9 fL78-100
Body_ID: T004002.500
mean corpuscular hemoglobin, MCH21.3 pg/cell25-35
Body_ID: T004002.550
mean corpuscular hemoglobin concentration, MCHC29.6 g/dL31-37
Body_ID: T004002.600
red cell distribution width, RDW17.7%11.5-14.5
Body_ID: T004002.650
platelet count, PLT274 ×103/mm3150-400 ×103
Body_ID: T004002.700
mean platelet volume,MPV8.6 fL6.4-11.0
Body_ID: T004002.750
Body_ID: T004002.800
Body_ID: T004002

*A Kratz and KB Lewandrowski (1998) Normal reference laboratory values. New Engl J Med 339:1063-1072
Automated laboratory evaluation of blood provides invaluable information for the diagnosis and monitoring of health problems. The complete blood count (CBC) includes cell counts of erythrocytes, white cells, and platelets and quantitative indices of the red cells (MCV, MCH, MCHC, and RDW). The results describe the hematopoietic status of the bone marrow and the presence of anemia and its possible cause. Data presented are characteristic of an individual with iron deficiency anemia: low HGB, low MCV (microcytosis), and low MCH (hypochromia). mm3 =μL.
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COMPLETE BLOOD COUNT
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A complete blood count (CBC) provides information on blood cell populations and their characteristics. Data are obtained from whole blood samples by automated hematology analysis. Some instruments also provide leukocyte differentials, reticulocyte count, and red cell morphology. A typical printout of the results for one individual and the range for normals is shown in Table 4.2.
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