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Hb SS disease(SCD)

MedGen UID:
287
Concept ID:
C0002895
Disease or Syndrome
Synonyms: HbS disease; Hemoglobin S Disease; Hemoglobin SS; SCD; Sickle cell anemia; Sickle cell disease; Sickling disorder due to hemoglobin S
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Hemoglobin S-S disease (127040003); Drepanocythemia (127040003); Hb SS disease (127040003); Sickling disorder due to hemoglobin S (417357006); Sickle cell disease (417357006); Sickle cell syndrome (417357006); Hereditary hemoglobinopathy disorder homozygous for hemoglobin S (127040003); Sickle cell anemia (127040003); Hemoglobin S disease (127040003); Hb S disease (127040003)
 
Gene (location): HBB (11p15.4)
OMIM®: 603903
Orphanet: ORPHA232

Definition

Sickle cell disease (SCD) is characterized by intermittent vaso-occlusive events and chronic hemolytic anemia. Vaso-occlusive events result in tissue ischemia leading to acute and chronic pain as well as organ damage that can affect any organ system, including the bones, spleen, liver, brain, lungs, kidneys, and joints. Dactylitis (pain and/or swelling of the hands or feet) is often the earliest manifestation of SCD. In children, the spleen can become engorged with blood cells in a “splenic sequestration.” The spleen is particularly vulnerable to infarction and the majority of individuals with SCD who are not on hydroxyurea or transfusion therapy become functionally asplenic in early childhood, increasing their risk for certain types of bacterial infections. Acute chest syndrome is a major cause of mortality in SCD. Chronic hemolysis can result in varying degrees of anemia, jaundice, cholelithiasis, and delayed growth and sexual maturation. Individuals with the highest rates of hemolysis are predisposed to pulmonary artery hypertension, priapism, and leg ulcers but may be relatively protected from vaso-occlusive pain. [from GTR]

Additional descriptions

From GeneReviews
Sickle cell disease (SCD) is characterized by intermittent vaso-occlusive events and chronic hemolytic anemia. Vaso-occlusive events result in tissue ischemia leading to acute and chronic pain as well as organ damage that can affect any organ system, including the bones, spleen, liver, brain, lungs, kidneys, and joints. Dactylitis (pain and/or swelling of the hands or feet) is often the earliest manifestation of SCD. In children, the spleen can become engorged with blood cells in a “splenic sequestration.” The spleen is particularly vulnerable to infarction and the majority of individuals with SCD who are not on hydroxyurea or transfusion therapy become functionally asplenic in early childhood, increasing their risk for certain types of bacterial infections. Acute chest syndrome is a major cause of mortality in SCD. Chronic hemolysis can result in varying degrees of anemia, jaundice, cholelithiasis, and delayed growth and sexual maturation. Individuals with the highest rates of hemolysis are predisposed to pulmonary artery hypertension, priapism, and leg ulcers but may be relatively protected from vaso-occlusive pain.  https://www.ncbi.nlm.nih.gov/books/NBK1377
From OMIM
Sickle cell anemia is a multisystem disease associated with episodes of acute illness and progressive organ damage. Hemoglobin polymerization, leading to erythrocyte rigidity and vasoocclusion, is central to the pathophysiology of the disease, but the importance of chronic anemia, hemolysis, and vasculopathy has been established. The most common cause of sickle cell anemia is the HbS variant (141900.0243), with hemoglobin SS disease being most prevalent in Africans (review by Rees et al., 2010). See review of infection in sickle cell disease by Booth et al. (2010). Piel et al. (2017) reviewed the genetic and nongenetic modifiers of the severity of sickle cell disease.  http://www.omim.org/entry/603903
From GHR
Sickle cell disease is a group of disorders that affects hemoglobin, the molecule in red blood cells that delivers oxygen to cells throughout the body. People with this disorder have atypical hemoglobin molecules called hemoglobin S, which can distort red blood cells into a sickle, or crescent, shape.Signs and symptoms of sickle cell disease usually begin in early childhood. Characteristic features of this disorder include a low number of red blood cells (anemia), repeated infections, and periodic episodes of pain. The severity of symptoms varies from person to person. Some people have mild symptoms, while others are frequently hospitalized for more serious complications.The signs and symptoms of sickle cell disease are caused by the sickling of red blood cells. When red blood cells sickle, they break down prematurely, which can lead to anemia. Anemia can cause shortness of breath, fatigue, and delayed growth and development in children. The rapid breakdown of red blood cells may also cause yellowing of the eyes and skin, which are signs of jaundice. Painful episodes can occur when sickled red blood cells, which are stiff and inflexible, get stuck in small blood vessels. These episodes deprive tissues and organs of oxygen-rich blood and can lead to organ damage, especially in the lungs, kidneys, spleen, and brain. A particularly serious complication of sickle cell disease is high blood pressure in the blood vessels that supply the lungs (pulmonary hypertension). Pulmonary hypertension occurs in about one-third of adults with sickle cell disease and can lead to heart failure.  https://ghr.nlm.nih.gov/condition/sickle-cell-disease

Clinical features

Retinopathy
MedGen UID:
11209
Concept ID:
C0035309
Disease or Syndrome
An abnormal structure or function of the retina and its associated tissues.
Hematuria
MedGen UID:
5488
Concept ID:
C0018965
Disease or Syndrome
Blood in the urine.
Priapism
MedGen UID:
19462
Concept ID:
C0033117
Disease or Syndrome
A painful and harmful medical condition in which the erect penis doesn't return to its flaccid state, despite the absence of both physical and psychological stimulation, within four hours.
Impaired renal concentrating ability
MedGen UID:
395351
Concept ID:
C1859819
Finding
A defect in the ability to concentrate the urine.
Cardiomegaly
MedGen UID:
5459
Concept ID:
C0018800
Finding
Abnormal enlargement of the heart.
Cholelithiasis
MedGen UID:
3039
Concept ID:
C0008350
Disease or Syndrome
Hard, pebble-like deposits that form within the gallbladder.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormal enlargement of the liver.
Jaundice
MedGen UID:
43987
Concept ID:
C0022346
Sign or Symptom
A clinical manifestation of HYPERBILIRUBINEMIA, characterized by the yellowish staining of the SKIN; MUCOUS MEMBRANE; and SCLERA. Clinical jaundice usually is a sign of LIVER dysfunction.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal enlargement of the spleen.
Congenital dyserythropoietic anemia
MedGen UID:
8064
Concept ID:
C0002876
Disease or Syndrome
A familial disorder characterized by ANEMIA with multinuclear ERYTHROBLASTS, karyorrhexis, asynchrony of nuclear and cytoplasmic maturation, and various nuclear abnormalities of bone marrow erythrocyte precursors (ERYTHROID PRECURSOR CELLS). Type II is the most common of the 3 types; it is often referred to as HEMPAS, based on the Hereditary Erythroblast Multinuclearity with Positive Acidified Serum test.
Hemolytic anemia
MedGen UID:
1916
Concept ID:
C0002878
Disease or Syndrome
A condition of inadequate circulating red blood cells (ANEMIA) or insufficient HEMOGLOBIN due to premature destruction of red blood cells (ERYTHROCYTES).
Microcytic anemia
MedGen UID:
39081
Concept ID:
C0085576
Disease or Syndrome
Finberg et al. (2008) referred to this phenotype as iron-refractory iron deficiency anemia (IRIDA) and reviewed the key features: a congenital hypochromic, microcytic anemia; a very low mean corpuscular erythrocyte volume; a low transferrin saturation; abnormal iron absorption characterized by no hematologic improvement following treatment with oral iron; and abnormal iron utilization characterized by a sluggish, incomplete response to parenteral iron. The authors noted that although urinary levels of hepcidin (606464) are typically undetectable in individuals with iron deficiency, in 5 individuals with IRIDA urinary hepcidin/creatinine ratios were within or above the normal range.
Persistence of hemoglobin F
MedGen UID:
68693
Concept ID:
C0239941
Finding
A laboratory test result indicating an abnormal amount of fetal hemoglobin in a biological sample.
Heinz body anemia
MedGen UID:
148583
Concept ID:
C0700299
Disease or Syndrome
Anemia characterized by abnormal intracellular inclusions, composed of denatured hemoglobin, found on the membrane of red blood cells.
Erythrocytosis
MedGen UID:
282903
Concept ID:
C1527405
Finding
Abnormally high level of red blood cells in the blood.(NICHD)
Increased red cell sickling tendency
MedGen UID:
870257
Concept ID:
C4024695
Finding
Macrocytic hemolytic disease
MedGen UID:
870731
Concept ID:
C4025185
Disease or Syndrome
Cyanosis
MedGen UID:
1189
Concept ID:
C0010520
Sign or Symptom
A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule.
Hematuria
MedGen UID:
5488
Concept ID:
C0018965
Disease or Syndrome
Blood in the urine.
Priapism
MedGen UID:
19462
Concept ID:
C0033117
Disease or Syndrome
A painful and harmful medical condition in which the erect penis doesn't return to its flaccid state, despite the absence of both physical and psychological stimulation, within four hours.
Impaired renal concentrating ability
MedGen UID:
395351
Concept ID:
C1859819
Finding
A defect in the ability to concentrate the urine.
Osteomyelitis
MedGen UID:
10497
Concept ID:
C0029443
Disease or Syndrome
An acute or chronic inflammation of the bone and its structures due to infection with pyogenic bacteria.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal enlargement of the spleen.
Hematuria
MedGen UID:
5488
Concept ID:
C0018965
Disease or Syndrome
Blood in the urine.
Osteomyelitis
MedGen UID:
10497
Concept ID:
C0029443
Disease or Syndrome
An acute or chronic inflammation of the bone and its structures due to infection with pyogenic bacteria.
Aseptic necrosis
MedGen UID:
508355
Concept ID:
C0085660
Pathologic Function
A disease where there is cellular death (necrosis) of bone components due to interruption of the blood supply.
Cyanosis
MedGen UID:
1189
Concept ID:
C0010520
Sign or Symptom
A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule.
Jaundice
MedGen UID:
43987
Concept ID:
C0022346
Sign or Symptom
A clinical manifestation of HYPERBILIRUBINEMIA, characterized by the yellowish staining of the SKIN; MUCOUS MEMBRANE; and SCLERA. Clinical jaundice usually is a sign of LIVER dysfunction.

Professional guidelines

PubMed

Traeger-Synodinos J, Harteveld CL, Old JM, Petrou M, Galanello R, Giordano P, Angastioniotis M, De la Salle B, Henderson S, May A; EMQN haemoglobinopathies best practice meeting.
Eur J Hum Genet 2015 Apr;23(4):426-37. Epub 2014 Jul 23 doi: 10.1038/ejhg.2014.131. PMID: 25052315Free PMC Article
Meschia JF, Bushnell C, Boden-Albala B, Braun LT, Bravata DM, Chaturvedi S, Creager MA, Eckel RH, Elkind MS, Fornage M, Goldstein LB, Greenberg SM, Horvath SE, Iadecola C, Jauch EC, Moore WS, Wilson JA; American Heart Association Stroke Council.; Council on Cardiovascular and Stroke Nursing.; Council on Clinical Cardiology.; Council on Functional Genomics and Translational Biology.; Council on Hypertension.
Stroke 2014 Dec;45(12):3754-832. Epub 2014 Oct 28 doi: 10.1161/STR.0000000000000046. PMID: 25355838Free PMC Article
Yawn BP, Buchanan GR, Afenyi-Annan AN, Ballas SK, Hassell KL, James AH, Jordan L, Lanzkron SM, Lottenberg R, Savage WJ, Tanabe PJ, Ware RE, Murad MH, Goldsmith JC, Ortiz E, Fulwood R, Horton A, John-Sowah J
JAMA 2014 Sep 10;312(10):1033-48. doi: 10.1001/jama.2014.10517. PMID: 25203083
Lin KW
Am Fam Physician 2009 Mar 15;79(6):507-8. PMID: 19323364
Genet Med 2006 May;8 Suppl 1:1S-252S. doi: 10.1097/01.gim.0000223891.82390.ad. PMID: 16783161Free PMC Article
Int J Gynaecol Obstet 1996 May;53(2):184-94. PMID: 8735302

External

American College of Medical Genetics ACT SHEET, Sickle Cell Anemia, 2010

American College of Medical Genetics Algorithm, Hb S Screening, 2009

Recent clinical studies

Etiology

Oleske DA, Huang RS, Dasgupta A, Nguyen A, Wahed A
Ann Clin Lab Sci 2014 Summer;44(3):291-3. PMID: 25117100
Allareddy V, Roy A, Lee MK, Nalliah RP, Rampa S, Allareddy V, Rotta AT
PLoS One 2014;9(4):e94387. Epub 2014 Apr 16 doi: 10.1371/journal.pone.0094387. PMID: 24740290Free PMC Article
Lagunju IA, Brown BJ
Int J Hematol 2012 Dec;96(6):710-8. Epub 2012 Nov 6 doi: 10.1007/s12185-012-1204-9. PMID: 23129067
Lagunju I, Sodeinde O, Telfer P
Am J Hematol 2012 May;87(5):544-7. Epub 2012 Mar 28 doi: 10.1002/ajh.23152. PMID: 22460323
King L, MooSang M, Miller M, Reid M
Arch Dis Child 2011 Dec;96(12):1135-9. Epub 2011 Sep 30 doi: 10.1136/archdischild-2011-300628. PMID: 21965808

Diagnosis

Oleske DA, Huang RS, Dasgupta A, Nguyen A, Wahed A
Ann Clin Lab Sci 2014 Summer;44(3):291-3. PMID: 25117100
Lagunju IA, Brown BJ
Int J Hematol 2012 Dec;96(6):710-8. Epub 2012 Nov 6 doi: 10.1007/s12185-012-1204-9. PMID: 23129067
Sherer DM, Dalloul M, Salameh G, Abulafia O
Obstet Gynecol 2009 Aug;114(2 Pt 2):471-2. doi: 10.1097/AOG.0b013e3181ac4e18. PMID: 19622965
Gorman MJ, Nyström K, Carbonella J, Pearson H
Neurology 2009 Aug 4;73(5):362-5. Epub 2009 Jun 24 doi: 10.1212/WNL.0b013e3181ae2361. PMID: 19553593
King L, Fraser R, Forbes M, Grindley M, Ali S, Reid M
J Med Screen 2007;14(3):117-22. doi: 10.1258/096914107782066185. PMID: 17925083

Therapy

Markham MJ, Lottenberg R, Zumberg M
Am J Hematol 2003 Jun;73(2):121-5. doi: 10.1002/ajh.10328. PMID: 12749014
Fatunde OJ, Sodeinde O, Familusi JB
Afr J Med Med Sci 2000 Sep-Dec;29(3-4):227-8. PMID: 11713995
Baker DL, Manno CS
Am J Hematol 1988 Dec;29(4):230-2. PMID: 3189321
Bertles JF, Milner PF
J Clin Invest 1968 Aug;47(8):1731-41. doi: 10.1172/JCI105863. PMID: 5666109Free PMC Article

Prognosis

Allareddy V, Roy A, Lee MK, Nalliah RP, Rampa S, Allareddy V, Rotta AT
PLoS One 2014;9(4):e94387. Epub 2014 Apr 16 doi: 10.1371/journal.pone.0094387. PMID: 24740290Free PMC Article
Lagunju IA, Brown BJ
Int J Hematol 2012 Dec;96(6):710-8. Epub 2012 Nov 6 doi: 10.1007/s12185-012-1204-9. PMID: 23129067
King L, MooSang M, Miller M, Reid M
Arch Dis Child 2011 Dec;96(12):1135-9. Epub 2011 Sep 30 doi: 10.1136/archdischild-2011-300628. PMID: 21965808
Gorman MJ, Nyström K, Carbonella J, Pearson H
Neurology 2009 Aug 4;73(5):362-5. Epub 2009 Jun 24 doi: 10.1212/WNL.0b013e3181ae2361. PMID: 19553593
Markham MJ, Lottenberg R, Zumberg M
Am J Hematol 2003 Jun;73(2):121-5. doi: 10.1002/ajh.10328. PMID: 12749014

Clinical prediction guides

Allareddy V, Roy A, Lee MK, Nalliah RP, Rampa S, Allareddy V, Rotta AT
PLoS One 2014;9(4):e94387. Epub 2014 Apr 16 doi: 10.1371/journal.pone.0094387. PMID: 24740290Free PMC Article
King L, MooSang M, Miller M, Reid M
Arch Dis Child 2011 Dec;96(12):1135-9. Epub 2011 Sep 30 doi: 10.1136/archdischild-2011-300628. PMID: 21965808
Gorman MJ, Nyström K, Carbonella J, Pearson H
Neurology 2009 Aug 4;73(5):362-5. Epub 2009 Jun 24 doi: 10.1212/WNL.0b013e3181ae2361. PMID: 19553593
Westerman MP, Green D, Gilman-Sachs A, Beaman K, Freels S, Boggio L, Allen S, Schlegel R, Williamson P
Am J Hematol 2002 Feb;69(2):89-94. PMID: 11835343
el-Hazmi MA, al-Swailem A, Warsy AS
J Trop Pediatr 1995 Aug;41(4):225-9. PMID: 7563275

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