| 词条 | Hereditary spherocytosis | ||||||||||||||||||||||||
| 释义 |
| name = Hereditary spherocytosis | synonyms = Minkowski–Chauffard syndrome | image = Hereditary Spherocytosis smear 2010-03-17.JPG | caption = Peripheral blood smear from patient with hereditary spherocytosis | pronounce = | field = Hematology | symptoms = | complications = | onset = | duration = | types = | causes = | risks = | diagnosis = | differential = | prevention = | treatment = | medication = | prognosis = | frequency = | deaths = }} Hereditary spherocytosis is an abnormality of red blood cells, or erythrocytes. The disorder is caused by mutations in genes relating to membrane proteins that allow for the erythrocytes to change shape. The abnormal erythrocytes are sphere-shaped (spherocytosis) rather than the normal biconcave disk shaped. Dysfunctional membrane proteins interfere with the cell's ability to be flexible to travel from the arteries to the smaller capillaries. This difference in shape also makes the red blood cells more prone to rupture.[1] Cells with these dysfunctional proteins are degraded in the spleen. This shortage of erythrocytes results in hemolytic anemia. It was first described in 1871. It is the most common cause of inherited hemolysis in European and North American Caucasian populations, with an incidence of 1 in 5000 births. The clinical severity of HS varies from symptom-free carrier to severe hemolysis because the disorder exhibits incomplete penetrance in its expression. Symptoms include anemia, jaundice, splenomegaly, and fatigue.[2] Furthermore, the detritus of the broken-down blood cells – unconjugated or indirect bilirubin – accumulates in the gallbladder, and can cause pigmented gallstones to develop. In chronic patients, an infection or other illness can cause an increase in the destruction of red blood cells, resulting in the appearance of acute symptoms, a hemolytic crisis. On a blood smear, Howell-Jolly bodies may be seen within red blood cells. Primary treatment for patients with symptomatic HS has been total splenectomy, which eliminates the hemolytic process, allowing normal hemoglobin, reticulocyte and bilirubin levels. Acute cases can threaten to cause hypoxia through anemia and acute kernicterus through high blood levels of bilirubin, particularly in newborns. Most cases can be detected soon after birth. An adult with this disease should have their children tested, although the presence of the disease in children is usually noticed soon after birth. Occasionally, the disease will go unnoticed until the child is about 4 or 5 years of age. A person may also be a carrier of the disease and show no signs or symptoms of the disease. Other symptoms may include abdominal pain that could lead to the removal of the spleen and/or gallbladder. Spherocytosis patients who are heterozygous for a hemochromatosis gene may suffer from iron overload, despite the hemochromatosis genes being recessive.[3][4] PresentationComplications
PathophysiologyHereditary spherocytosis can be an autosomal recessive or autosomal dominant trait.[9] Hereditary spherocytosis is most commonly (though not exclusively) found in Northern European and Japanese families, although an estimated 25% of cases are due to spontaneous mutations. A patient has a 50% chance of passing the mutation onto each of his/her offspring. Hereditary spherocytosis is caused by a variety of molecular defects in the genes that code for the red blood cell proteins spectrin (alpha and beta), ankyrin,[10] band 3 protein, protein 4.2,[11] and other red blood cell membrane proteins:[12]
These proteins are necessary to maintain the normal shape of a red blood cell, which is a biconcave disk. The integrating protein that is most commonly defective is spectrin which is responsible for incorporation and binding of spectrin, thus in its dysfunction cytoskeletal instabilities ensue. The primary defect in hereditary spherocytosis is a deficiency of membrane surface area. Decreased surface area may be produced by two different mechanisms: 1) Defects of spectrin, ankyrin (most commonly), or protein 4.2 lead to reduced density of the membrane skeleton, destabilizing the overlying lipid bilayer and releasing band 3-containing microvesicles. 2) Defects of band 3 lead to band 3 deficiency and loss of its lipid-stabilizing effect. This results in the loss of band 3-free microvesicles. Both pathways result in membrane loss, decreased surface area, and formation of spherocytes with decreased deformability. As the spleen normally targets abnormally shaped red cells (which are typically older), it also destroys spherocytes. In the spleen, the passage from the cords of Billroth into the sinusoids may be seen as a bottleneck, where red blood cells need to be flexible in order to pass through. In hereditary spherocytosis, red blood cells fail to pass through and get phagocytosed, causing extravascular hemolysis.[12] DiagnosisIn a peripheral blood smear, the red blood cells will appear abnormally small and lack the central pale area that is present in normal red blood cells. These changes are also seen in non-hereditary spherocytosis, but they are typically more pronounced in hereditary spherocytosis. The number of immature red blood cells (reticulocyte count) will be elevated.[2] An increase in the mean corpuscular hemoglobin concentration is also consistent with hereditary spherocytosis. Other protein deficiencies cause hereditary elliptocytosis, pyropoikilocytosis or stomatocytosis. In longstanding cases and in patients who have taken iron supplementation or received numerous blood transfusions, iron overload may be a significant problem. This is a potential cause of heart muscle damage and liver disease. Measuring iron stores is therefore considered part of the diagnostic approach to hereditary spherocytosis. An osmotic fragility test can aid in the diagnosis.[13] In this test, the spherocytes will rupture in liquid solutions less concentrated than the inside of the red blood cell. This is due to increased permeability of the spherocyte membrane to salt and water, which enters the concentrated inner environment of the RBC and leads to its rupture.[14] Although the osmotic fragility test is widely considered the gold standard for diagnosing hereditary spherocytosis, it misses as many as 25% of cases. Flow cytometric analysis of eosin-5′-maleimide-labeled intact red blood cells and the acidified glycerol lysis test are two additional options to aid diagnosis.[15] TreatmentAlthough research is ongoing, at this point there is no cure for the genetic defect that causes hereditary spherocytosis.[12] Current management focuses on interventions that limit the severity of the disease. Treatment options include:
EpidemiologyHereditary spherocytosis is the most common disorder of the red cell membrane and affects 1 in 2,000 people of Northern European ancestry.[19] According to Harrison's Principles of Internal Medicine, the frequency is at least 1 in 5,000.[17] ResearchExperimental gene therapy exists to treat hereditary spherocytosis in lab mice; however, this treatment has not yet been tried on humans due to all of the risks involved in human gene therapy. See also
References1. ^{{cite book |author1=Cotran, Ramzi S. |author2=Kumar, Vinay |author3=Fausto, Nelson |author4=Nelso Fausto |author5=Robbins, Stanley L. |author6=Abbas, Abul K. |title=Robbins and Cotran pathologic basis of disease |publisher=Elsevier Saunders |location=St. Louis, Mo |year=2005 |page=625 |isbn=0-7216-0187-1 |oclc= |doi= |accessdate=}} 2. ^1 2 3 4 {{Cite journal | last1 = Bolton-Maggs | first1 = P. H. B. | last2 = Stevens | first2 = R. F. | last3 = Dodd | first3 = N. J. | last4 = Lamont | first4 = G. | last5 = Tittensor | first5 = P. | last6 = King | first6 = M. -J. | author7 = General Haematology Task Force of the British Committee for Standards in Haematology | doi = 10.1111/j.1365-2141.2004.05052.x | title = Guidelines for the diagnosis and management of hereditary spherocytosis | journal = British Journal of Haematology | volume = 126 | issue = 4 | pages = 455–474 | year = 2004 | pmid = 15287938 | pmc = }} 3. ^{{cite web|author1=J L Rasmussen |author2=D A Odelson |author3=F L Macrina |url=http://ukpmc.ac.uk/classic/articlerender.cgi?artid=1296185 |archive-url=https://archive.is/20121223070533/http://ukpmc.ac.uk/classic/articlerender.cgi?artid=1296185 |dead-url=yes |archive-date=2012-12-23 |title=Complete nucleotide sequence of insertion element IS4351 from Bacteroides fragilis. - UKPMC Article - UK PubMed Central |publisher=UKPMC Article |date=1987-08-01 |accessdate=2012-07-03 }} 4. ^{{cite web |url=http://www.bcshguidelines.com/documents/HS_BCSH_Sept_2011_final.pdf |title=Guidelines for the Diagnosis and Management of Hereditary Spherocytosis |author=Paula Bolton-Maggs |date=September 2011 |work= |publisher=The British Committee for Standards in Haematology |accessdate=2 July 2012}} 5. ^{{Cite journal | last1 = Fjaerli | first1 = H. 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Dis. |volume=24 |issue=4 |pages=539–43 |date=December 1998 |pmid=9887280 |doi=10.1006/bcmd.1998.0217 |url=http://linkinghub.elsevier.com/retrieve/pii/S1079-9796(98)90217-0}} 11. ^{{cite journal |vauthors=Perrotta S, Gallagher PG, Mohandas N |title=Hereditary spherocytosis |journal=Lancet |volume=372 |issue=9647 |pages=1411–26 |date=October 2008 |pmid=18940465 |doi=10.1016/S0140-6736(08)61588-3 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(08)61588-3}} 12. ^Chapter 12, page 425 in: {{cite book |author1=Mitchell, Richard Sheppard |author2=Kumar, Vinay |author3=Abbas, Abul K. |author4=Fausto, Nelson |title=Robbins Basic Pathology|publisher=Saunders |location=Philadelphia |pages= |isbn=1-4160-2973-7 |oclc= |doi=}} 8th edition. 13. ^{{cite journal |vauthors=Won DI, Suh JS |title=Flow cytometric detection of erythrocyte osmotic fragility |journal=Cytometry Part B |volume=76 |issue=2 |pages=135–41 |date=March 2009 |pmid=18727072 |doi=10.1002/cyto.b.20448}} 14. ^Goljan. Rapid Review Pathology. 2010. Page 213. 15. ^{{Cite journal | last1 = Bianchi | first1 = P. | last2 = Fermo | first2 = E. | last3 = Vercellati | first3 = C. | last4 = Marcello | first4 = A. P. | last5 = Porretti | first5 = L. | last6 = Cortelezzi | first6 = A. | last7 = Barcellini | first7 = W. | last8 = Zanella | first8 = A. | doi = 10.3324/haematol.2011.052845 | title = Diagnostic power of laboratory tests for hereditary spherocytosis: A comparison study in 150 patients grouped according to molecular and clinical characteristics | journal = Haematologica | volume = 97 | issue = 4 | pages = 516–523 | year = 2011 | pmid = 22058213 | pmc =3347664 }} 16. ^{{cite journal |vauthors=Bolton-Maggs PH, Stevens RF, Dodd NJ, Lamont G, Tittensor P, King MJ |title=Guidelines for the diagnosis and management of hereditary spherocytosis |journal=Br. J. Haematol. |volume=126 |issue=4 |pages=455–74 |date=August 2004 |pmid=15287938 |doi=10.1111/j.1365-2141.2004.05052.x}} 17. ^1 2 3 4 {{cite book|author1=Anthony S. Fauci |author2=Eugene Braunwald |author3=Dennis L. Kasper |author4=Stephen L. Hauser |author5=Dan L. Longo |author6=J. Larry Jameson |author7=Joseph Loscalzo |title=Harrison's principles of internal medicine|year=2008|publisher=McGraw-Hill Medical|location=New York|isbn=978-0071466332|pages=Chapter 106|url=http://www.accessmedicine.com/content.aspx?aID=9117899|edition=17th}} 18. ^{{Cite journal | last1 = Buesing | first1 = K. L. | last2 = Tracy | first2 = E. T. | last3 = Kiernan | first3 = C. | last4 = Pastor | first4 = A. C. | last5 = Cassidy | first5 = L. D. | last6 = Scott | first6 = J. P. | last7 = Ware | first7 = R. E. | last8 = Davidoff | first8 = A. M. | last9 = Rescorla | first9 = F. J. | last10 = Langer | doi = 10.1016/j.jpedsurg.2010.09.090 | first10 = J. C. | last11 = Rice | first11 = H. E. | last12 = Oldham | first12 = K. T. | title = Partial splenectomy for hereditary spherocytosis: A multi-institutional review | journal = Journal of Pediatric Surgery | volume = 46 | issue = 1 | pages = 178–183 | year = 2011 | pmid = 21238662 | pmc = }} 19. ^https://ghr.nlm.nih.gov/condition/hereditary-spherocytosis#genes External links{{Medical resources| ICD10 = {{ICD10|D|58|0|d|55}} | ICD9 = {{ICD9|282.0}} | ICDO = | OMIM = 182900 | MedlinePlus = 000530 | eMedicineSubj = med | eMedicineTopic = 2147 | MeshID = D013103 }}
3 : Hereditary hemolytic anemias|Cytoskeletal defects|Autosomal dominant disorders |
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