מיקרוספרוציטוזיס

בני בן שנה. התגלתה אצלו לאחרונה המחלה מיקרוספרוציטוזיס. אשמח לדעת יותר על מחלה זו, ואם תוכל להפנות אותי לאתרים בנושא , אשמח מאד.

שלום רחלי מיקרוספרוציטוזיס כשלעצמה אינה שם של מחלה אלא תיאור של מורפולוגיית הכדוריות האדומות בדם ההיקפי. אינני יודע מה המחלה שאובחנה אצל בנך --> יש מספר מחלות העלולות לגרום להופעת מיקרוספרוציטים בדם והן: ספרוציטוזיס תורשתית אנמיה המוליטית בגלל נוגדנים אנמיה המוליטית בגלל המוגלובין לא יציב ("גופיפי היינץ") המיקרוספוציטים הם כדוריות אדומות אשר איבדו חלק מהממברנה שלהם בגלל פגם מבני של חלבונים מסויימים (ספקטרין) המרכיבים את הממברנה (ספרוציטוזיס) או בגלל "נגיסת" חלק מהממברנה ע"י תאים מקרופגים בטחול וזאת בגלל הנוגדנים שעל הממברנה (אנמיה המוליטית אוטואימונית) או בגלל התגבשות המוגלובין פתולוגי בתוך הכדורית (המוגלובין לא יציב). בלינק הבא תוכלי למצוא מידע על אנמיות המוליטיות מסוגים שונים, ביניהם 3 המחלות שהזכרתי לעיל: http://www.merck.com/pubs/mmanual/section11/chapter127/127d.htm אני מחפש עוד לינקים

תקצירים אלה מתייחסים לספרוציטוזיס תורשתית Semin Hematol 1999 Oct;36(4 Suppl 7):38-47 Hemolytic anemia. Beutler E, Luzzatto L Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA. We entered the 20th century with only meager understanding of the erythrocyte. We leave this century with a relatively detailed understanding of the metabolism of the erythrocyte, the structure of its membrane, and the basis of genetic disorders that lead to its early demise in hemolytic anemia. Among the immune hemolytic disorders, the conquest of Rh hemolytic disease is one of the important clinical achievements of this century. Hereditary disorders of the membrane generally cause shape changes, such as spherocytosis or ovalocytosis. Paroxysmal nocturnal hemoglobinuria is the result of an acquired (somatic) mutation of PIG-A, an X-linked component of the glycosylphosphatidylinositol (GPI) anchor. Red cell enzyme deficiencies cause hereditary nonspherocytic hemolytic anemia. The mutations that cause the more common of these deficiencies are now well understood at the DNA level. Although much progress has been made, much is still to be learned. In particular, management of both acquired and hereditary hemolytic anemias is still very unsatisfactory. Often the only decision that can be made is whether to perform a splenectomy. In the future it is to be hoped that the knowledge that has been gained about these disorders in this century will make available better therapy to our patients in the next **************************************************************************** כדי לקרוא מאמר זה בשלמותו כדאי לספריה רפואית (באוניברסיטה או בבית חולים ולמצוא את העיתון) Br J Haematol 1999 Jan;104(1):2-13 Red blood cell membrane disorders. Tse WT, Lux SE Division of Hematology/Oncology, Children's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. The recent discovery of the specific molecular defects in many patients with hereditary spherocytosis and hereditary elliptocytosis/pyropoikilocytosis partially clarifies the molecular pathology of these diseases. HE and HPP are caused by defects in the horizontal interactions that hold the membrane skeleton together, particularly the critical spectrin self-association reaction. Single gene defects cause red cells to elongate as they circulate, by a unknown mechanism, and are clinically harmless. The combination of two defective genes or one severe alpha spectrin defect and a thalassaemia-like defect in the opposite allele (alphaLELY) results in fragile cells that fragment into bizarre shapes in the circulation, with haemolysis and sometimes life-threatening anaemia. A few of the alpha spectrin defects are common, suggesting they provide an advantage against malaria or some other threat. HS, in contrast, is nearly always caused by family-specific private mutations. These involve the five proteins that link the membrane skeleton to the overlying lipid bilayer: alpha and beta spectrin, ankyrin, band 3 and protein 4.2. Somehow, perhaps through loss of the anchorage band 3 provides its lipid neighbours (Peters et al, 1996), microvesiculation of the membrane surface ensues, leading to spherocytosis, splenic sequestration and haemolysis. Future research will need to focus on how each type of defect causes its associated disease, how the spleen aggravates membrane skeleton defects (a process termed 'conditioning'), how defective red, cells are recognized and removed in the spleen, and why patients with similar or even identical defects can have different clinical severity. Emphasis also needs to be given to improving diagnostic tests, particularly for HS, and exploring new options for therapy, like partial splenectomy, which can ameliorate symptoms while better protecting patients from bacterial sepsis and red cell parasites, and perhaps from atherosclerosis (Robinette & Franmeni, 1977) and venous thrombosis (Stewart et al, 1996). *************************************************************************************** Haematologica 1998 Mar;83(3):240-57 Hereditary spherocytosis: from clinical to molecular defects. Iolascon A, Miraglia del Giudice E, Perrotta S, Alloisio N, Morle L, Delaunay J Dipartimento di Biomedicina dell'Eta Evolutiva, Universita degli Studi di Bari, Italy. [email protected] Resistance and elastic deformability of red cells are due to a protein network (cytoskeleton) that laminates the lipid bilayer and to proteins that span the latter. All proteins are interconnected. Their structure as well as the structure of the corresponding genes are now well known. Hereditary spherocytosis (HS) is the most common hemolytic anemia due to a red cell membrane defect. It derives from alterations of the following genes: ANK1, EPB3, ELB42, SPTA1 and SPTB. This condition is clinically, biochemically and genetically heterogeneous. The osmotically fragile spherocytes are selectively trapped in the spleen and destroyed. Increased red blood cell destruction causes the three main clinical signs of HS: anemia, jaundice and splenomegaly. In this review we analyze the most recent advances concerning the molecular basis and the clinical course of HS. In particular, we examine the major individual proteins that constitute the skeleton, which are now known to play an essential role in the pathogenesis of HS. This paper also includes a review of the therapeutical approach to HS. Concerning the diagnosis we provide a flow chart from the clinical aspects to the molecular diagnosis. ******************************************************************************************** Mol Membr Biol 1997 Oct-Dec;14(4):155-65 The structure and function of band 3 (AE1): recent developments (review). Tanner MJ Department of Biochemistry, School of Medical Sciences, University of Bristol, UK. This review discusses recent advances in our understanding of the structure, function and molecular genetics of the membrane domain of red cell anion exchanger, band 3 (AE1), and its role in red cell and kidney disease. A new model for the topology of band 3 has been proposed, which suggests the membrane domain has 12 membrane spans, rather than the 14 membrane spans of earlier models. The major difference between the models is in the topology of the region on the C-terminal side of membrane spans 1-7. Two dimensional crystals of the deglycosylated membrane domain of band 3 have yielded two and three dimensional projection maps of the membrane domain dimer at low resolution. The human band 3 gene has been completely sequenced and this has facilitated the study of natural band 3 mutations and their involvement in disease. About 20% of hereditary spherocytosis cases arise from heterozygosity for band 3 mutations, and result in the absence or decrease of the mutant protein in the red cell membrane. Several other natural band 3 mutations are known that appear to be clinically benign, but alter red cell phenotype or are associated with altered red cell blood group antigens. These include the mutant band 3 present in Southeast Asian ovalocytosis, a condition which provides protection against cerebral malaria in children. Familial distal renal tubular acidosis, a condition associated with kidney stones, has been shown to result from a novel group of band 3 mutations. The total absence of band 3 has been described in animals-occurring naturally in cattle and after targeted disruption in mice. Some of these severely anaemic animals survive, so band 3 is not strictly essential for life. Although the band 3-negative red cells were very unstable, they contained a normally-assembled red cell skeleton, suggesting that the bilayer of the normal red cell membrane is stabilized by band 3 interactions with membrane lipids, rather than by interactions with the spectrin skeleton.

גם את זה אפשר להשיג בספריות רפואיות Baillieres Best Pract Res Clin Haematol 2000 Sep;13(3):327-42 Related Articles, Books The diagnosis and management of hereditary spherocytosis. Bolton-Maggs PH Royal Liverpool Children's Hospital, Liverpool, UK. [Medline record in process] Hereditary spherocytosis (HS) is relatively common in Caucasian populations; most individuals have mild or only moderate disease. There is commonly a family history and a typical clinical and laboratory picture so that the diagnosis is usually easily made without additional laboratory tests. Atypical cases may require measurement of membrane proteins and molecular genetics to clarify the nature of the membrane disorder. It is particularly important to rule out stomatocytosis because splenectomy is contraindicated because of the thrombotic risk. Mild HS can be managed without folate supplements and does not require splenectomy. Moderately and severely affected individuals are likely to benefit from splenectomy, which should be performed after the age of 6 and with appropriate counselling about the risk of infection. In all cases careful dialogue between physician, child and the family is essential. Laparoscopic surgery can result in shorter hospital stay and less pain.

http://www.adam.com/imagepage/1220.htm?topic=TOP00000000000000000000000000530 ************************************************* http://www.mc.vanderbilt.edu/peds/pidl/hemeonc/spherocy.htm ***************************************************** http://medhlp.netusa.net/glossary/new/GLS_2227.HTM *************************************************** http://www.skiagram.com/p4-653.html *************************************************** http://www.drhull.com/EncyMaster/S/spherocytosis.html *********************************************** http://www.stepstn.com/cgi-win/nord.exe?proc=Redirect&type=rdb_sum&id=81.htm ******************************************** http://www.wadsworth.org/chemheme/heme/microscope/spherocyte.htm ******************************************** וזה על אנמיות המוליטיות: http://www.neosoft.com/~uthman/hemolytic_anemia/hemolytic_anemia.html