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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
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); Sickle cell-hemoglobin SS disease (127040003); Hemoglobin S disease (127040003); Hb S disease (127040003)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: 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 individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): HBB (11p15.4)
 
Monarch Initiative: MONDO:0011382
OMIM®: 603903
Orphanet: ORPHA232

Disease characteristics

Excerpted from the GeneReview: Sickle Cell Disease
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, primarily encapsulated organisms. Acute chest syndrome (ACS) 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 as well as activating pathways that contribute to the pathophysiology directly. Individuals with the highest rates of hemolysis are at higher risk for pulmonary artery hypertension, priapism, and leg ulcers and may be relatively protected from vaso-occlusive pain. [from GeneReviews]
Authors:
MA Bender  |  Katie Carlberg   view full author information

Additional descriptions

From OMIM
Sickle cell disease 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 MedlinePlus Genetics
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 disease 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, such as the lungs, kidneys, spleen, and brain, of oxygen-rich blood and can lead to organ damage. A particularly serious complication of sickle cell disease is high blood pressure in the blood vessels that supply the lungs (pulmonary hypertension), which can lead to heart failure. Pulmonary hypertension occurs in about 10 percent of adults with sickle cell disease.  https://medlineplus.gov/genetics/condition/sickle-cell-disease

Clinical features

From HPO
Abdominal pain
MedGen UID:
7803
Concept ID:
C0000737
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen.
Hematuria
MedGen UID:
5488
Concept ID:
C0018965
Disease or Syndrome
The presence of blood in the urine. Hematuria may be gross hematuria (visible to the naked eye) or microscopic hematuria (detected by dipstick or microscopic examination of 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.
Renal insufficiency
MedGen UID:
332529
Concept ID:
C1565489
Disease or Syndrome
A reduction in the level of performance of the kidneys in areas of function comprising the concentration of urine, removal of wastes, the maintenance of electrolyte balance, homeostasis of blood pressure, and calcium metabolism.
Cardiomegaly
MedGen UID:
5459
Concept ID:
C0018800
Finding
Increased size of the heart, clinically defined as an increased transverse diameter of the cardiac silhouette that is greater than or equal to 50% of the transverse diameter of the chest (increased cardiothoracic ratio) on a posterior-anterior projection of a chest radiograph or a computed tomography.
Hypertensive disorder
MedGen UID:
6969
Concept ID:
C0020538
Disease or Syndrome
The presence of chronic increased pressure in the systemic arterial system.
Stroke disorder
MedGen UID:
52522
Concept ID:
C0038454
Disease or Syndrome
Sudden impairment of blood flow to a part of the brain due to occlusion or rupture of an artery to the brain.
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
Abnormally increased size of the liver.
Jaundice
MedGen UID:
43987
Concept ID:
C0022346
Sign or Symptom
Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream.
Hemolytic anemia
MedGen UID:
1916
Concept ID:
C0002878
Disease or Syndrome
A type of anemia caused by premature destruction of red blood cells (hemolysis).
Target cells
MedGen UID:
526211
Concept ID:
C0221284
Cell
Target cells (codocytes) have a centrally located disk of hemoglobin surrounded by an area of pallor with an outer rim of hemoglobin adjacent to the cell membrane giving the cell the appearance of a target.
Increased red cell sickling tendency
MedGen UID:
870257
Concept ID:
C4024695
Finding
Hypoxemia
MedGen UID:
152145
Concept ID:
C0700292
Finding
An abnormally low level of blood oxygen.
Leukocytosis
MedGen UID:
9736
Concept ID:
C0023518
Disease or Syndrome
An abnormal increase in the number of leukocytes in the blood.
Splenic infarction
MedGen UID:
52468
Concept ID:
C0037998
Disease or Syndrome
Ischemia and necrosis of part or all of the spleen resulting from compromise of blood supply resulting from arterial or venous occlusion.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Recurrent bacterial infections
MedGen UID:
334943
Concept ID:
C1844383
Finding
Increased susceptibility to bacterial infections, as manifested by recurrent episodes of bacterial infection.
Retinopathy
MedGen UID:
11209
Concept ID:
C0035309
Disease or Syndrome
Any noninflammatory disease of the retina. This nonspecific term is retained here because of its wide use in the literature, but if possible new annotations should indicate the precise type of retinal abnormality.

Recent clinical studies

Etiology

Ionescu F, Anusim N, Zimmer M, Jaiyesimi I
Eur J Haematol 2022 Sep;109(3):282-288. Epub 2022 Jun 8 doi: 10.1111/ejh.13807. PMID: 35617049
Oleske DA, Huang RS, Dasgupta A, Nguyen A, Wahed A
Ann Clin Lab Sci 2014 Summer;44(3):291-3. PMID: 25117100
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
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. doi: 10.1002/ajh.10021. PMID: 11835343
Glader BE, Propper RD, Buchanan GR
Am J Clin Pathol 1979 Jul;72(1):63-4. doi: 10.1093/ajcp/72.1.63. PMID: 453112

Diagnosis

Ogu UO, Reyes Gil M, Tolu SS, Acharya SA, Minniti CP
Hemoglobin 2021 Mar;45(2):136-139. Epub 2021 Jun 16 doi: 10.1080/03630269.2021.1926276. PMID: 34134586
Alshehri E, Dmytriw AA, Chavhan GB, Amirabadi A, Shroff MM, Williams S, Muthusami P
J Stroke Cerebrovasc Dis 2020 Jul;29(7):104864. Epub 2020 May 10 doi: 10.1016/j.jstrokecerebrovasdis.2020.104864. PMID: 32402717
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
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

Russo K, Chhunchha P
J Pain Palliat Care Pharmacother 2023 Jun;37(2):116-122. Epub 2023 Jan 26 doi: 10.1080/15360288.2023.2167035. PMID: 36701332
Ionescu F, Anusim N, Zimmer M, Jaiyesimi I
Eur J Haematol 2022 Sep;109(3):282-288. Epub 2022 Jun 8 doi: 10.1111/ejh.13807. PMID: 35617049
Markham MJ, Lottenberg R, Zumberg M
Am J Hematol 2003 Jun;73(2):121-5. doi: 10.1002/ajh.10328. PMID: 12749014
Baker DL, Manno CS
Am J Hematol 1988 Dec;29(4):230-2. doi: 10.1002/ajh.2830290411. PMID: 3189321
Bertles JF, Milner PF
J Clin Invest 1968 Aug;47(8):1731-41. doi: 10.1172/JCI105863. PMID: 5666109Free PMC Article

Prognosis

Ionescu F, Anusim N, Zimmer M, Jaiyesimi I
Eur J Haematol 2022 Sep;109(3):282-288. Epub 2022 Jun 8 doi: 10.1111/ejh.13807. PMID: 35617049
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
Markham MJ, Lottenberg R, Zumberg M
Am J Hematol 2003 Jun;73(2):121-5. doi: 10.1002/ajh.10328. PMID: 12749014
Kehinde MO, Marsh JC, Marsh GW
Br J Haematol 1987 Aug;66(4):543-7. doi: 10.1111/j.1365-2141.1987.tb01342.x. PMID: 3663511

Clinical prediction guides

Ionescu F, Anusim N, Zimmer M, Jaiyesimi I
Eur J Haematol 2022 Sep;109(3):282-288. Epub 2022 Jun 8 doi: 10.1111/ejh.13807. PMID: 35617049
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
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. doi: 10.1002/ajh.10021. PMID: 11835343
el-Hazmi MA, al-Swailem A, Warsy AS
J Trop Pediatr 1995 Aug;41(4):225-9. doi: 10.1093/tropej/41.4.225. PMID: 7563275
Glader BE, Propper RD, Buchanan GR
Am J Clin Pathol 1979 Jul;72(1):63-4. doi: 10.1093/ajcp/72.1.63. PMID: 453112

Supplemental Content

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    Curated

    • ACMG ACT Sheet, 2023
      American College of Medical Genetics ACT SHEET, Sickle Cell Anemia, 2023
    • ACMG Algorithm, 2023
      ACMG Algorithm, FS: Hemoglobin S Screening Result, 2023
    • ACMG Algorithm, 2023
      ACMG Algorithm, FAS: Sickle Cell Trait Screening Result, 2023
    • ACMG ACT, 2023
      American College of Medical Genetics and Genomics, Carrier Screening ACT Sheet, Sickle Cell Carrier/Trait, 2023
    • ACMG ACT, 2012
      American College of Medical Genetics ACT SHEET, Newborn Screening ACT Sheet, [FAS] Sickle Cell Carrier (HbAS)
    • ACMG ACT, 2012
      American College of Medical Genetics and Genomics, Transition to Adult Health Care ACT Sheet, Sickle Cell Disease, 2012
    • ACMG Algorithm, 2009
      American College of Medical Genetics and Genomics, Algorithm, Hb S Screening, 2009

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