Anemia, sickle-cell

Electrospray mass spectra of globins from the blood of (a) a child diagnosed as having the sickle-cell anemia trait and (b) of its mother. As well as the usual p-globin sickle-cell variant at m/z 15,837.2, a new variant (P-Montreal-Chori) appears at m/z 15,879.3 and is observed in both the child and the mother. 

Sickle-cell anemia is the classic example of an inherited disease that is caused by a change in a protein s amino acid sequence. Linus Pauling proposed in 1949 that it was caused by a defect in the hemoglobin molecule he thus coined the term molecular disease. Seven years later Vernon Ingram showed that the disease was caused by a single mutation, a change in residue 6 of the P chain of hemoglobin from Glu to Val. 

In the body, proteins are built up by a series of reactions that in general produce a specific sequence of amino adds. Even tiny errors in this sequence may have serious effects. Among the genetic diseases known to be caused by improper sequencing are hemophilia, sickle cell anemia, and albinism. Sickle cell anemia is caused by the substitution of one valine unit for a glutamic add unit in a chain containing 146 monomers. 

Intermediate-conductance (IKCa) Sickle cell anemia, Diarrhea, Clotrimazole, ICA-15451 ICA-17043... 

Sebastian P, Ramoni ME, Nolan V, Baldwin CT, Steinberg MH. Genetic dissection and prognostic modeling of overt stroke in sickle cell anemia. Nat Genet 2005 37 435-40. 

Figure 1-1. Examples ofthe two-way street connecting biochemistry and medicine. Knowledge ofthe biochemical molecules shown in the top part of the diagram has clarified our understanding ofthe diseases shown in the bottom half—and conversely, analyses ofthe diseases shown below have cast light on many areas of biochemistry. Note that sickle cell anemia is a genetic disease and that both atherosclerosis and diabetes mellitus have genetic components.

Secondary kemochromatosis can occur after repeated transfusions (eg, for treatment of sickle cell anemia), excessive oral intake of iron (eg, by African Banm peoples who consume alcoholic beverages fermented in containers made of iron), or a number of other condi-... 

Sickle cell anemia (MIM 141900) Sequence of codon 6 of the p chain changed from GAG in the normal gene to GTG in the sickle cell gene, resulting in substitution of valine for glutamic acid... 

In sickle cell anemia by Pauling oX at. In 1949 (O was followed by the discovery of a large number of additional variants ... 

Mlcrochromatographlc Methods During the past two years rapid. Inexpensive, miniaturized column chromatographic methods for the separation of hemoglobins have been developed These methods are designed for the qualitative detection and quantitative determination of hemoglobins In normal and abnormal conditions and cover the quantitation of Hb-A2 the detection of Hb-S, Hb-C other abnormal Hbs differentiation of various conditions In adults and the detection of hemoglobinopathies especially sickle cell anemia at birth (27, 28, 29, 30) ... 

UicAochAornatogAoptiic TcAtcng MetkodA ioA Sickle, Cell Anemia and Related Vl60AdeAA in the AdixJit. The procedures described in the preceding Section are, in fact, applicable to the detection of hemoglobinopathies in the adult, and any quantitative determination of Hb-A2 immediately becomes a qualitative test for abnormal Hb s. If, instead of the very small zone of Hb-A2, a prominent zone moves in the same way, Hb-C (or Hb- ) is indicated. 

Figure 7. Microchromatography on DEAE-cellulose. A, The levels of Hb-At in normal adults, in p thalassemia heterozygotes, in Hb S traits, and in patients with sickle cell anemia and HbS-p-thalassemia (Georgia survey). B, The levels of Hb-At in normal adults and in p-thalassemia heterozygotes (Macedonia survey).

CoAd Blood Testing oa Sickle Cell Anemia and Related Vl6-oAdeAS by AlienachAomatogAaphlc Methods. The CM-Sephadex procedure easily detects Hb-S and Hb-C at birth but the diffuse zone of Hb-A has on occasion been difficult to see. Substitution of CM-Cellulose for CM-Sephadex has yielded a superior mlcrochromatographlc method, and the compact, well-defined zones of the CM-Cellulose column facilitate the Interpretation of the results even though the amount of sample Is only 20% as great. The CM-Cellulose method Is as simple and rapid as the original CM-Sephadex procedure (27. 28). 

Lunzer MM, Yekkirala A, Hebbel RP, Portoghese PS (2007) Naloxone acts as a potent analgesic in transgenic mouse models of sickle cell anemia. Proc Natl Acad Sci USA 104 6061-6065... 

Saiki RK, Schare S, Faloona F Muelis KB, Horn GT, Erlich HA, Arnheim N (1985) Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia Science 1985 Dec 20, 23o(4732) i35o-i354-... 

FIGURE 65-1. Sickle gene inheritance scheme for both parents with sickle cell trait (SCT). A, normal hemoglobin S, sickle hemoglobin. Possibilities with each pregnancy 25% normal (AA) 50% SCT (AS) 25% sickle cell anemia (SS). (From Chan CYJ, Moore R. Sickle cell disease. In DiPiro JT, Talbert RL, Yee GC, et al, (eds.) Pharmacotherapy A Pathophysiologic Approach. 6th ed. New York McGraw-Hill 2005 1856.)... 

Sickle cell anemia Fbinful vaso-occlusive crises are the... 

HbSC, sickle-hemoglobin C Hgb, hemoglobin RBC, red blood cell SCA, sickle cell anemia. 

She was diagnosed with sickle cell anemia at birth, identified through neonatal screening. Today, her hemoglobin is 8.6 g/dl (86 g/L or 5.3 mmol/L) and she is afebrile. 

Early detection of ischemic stroke can be done with the use of transcranial Doppler ultrasonography. In the Stroke Prevention Trial in Sickle Cell Anemia (STOP) study, screening with this method followed by transfusion significantly reduced the incidence of stroke.29 Screening is recommended in all patients over 2 years of age. 

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