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Accession information: Vol. 8; Issue 9; 28 April 2006 Abstract
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The spectrum of sickle cell disorders

Catherine Madigan and Punam Malik

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Table 1. The spectrum of sickle cell disorders

Disease

Genetic defect Hb produced Clinical consequencesa

HbSS
(Sickle cell anaemia)

Homozygous for substitution of valine for glutamine at sixth codon of b-globin gene

HbS
Variable HbF 		Moderate to severe anaemia, vaso-occlusive episodes, strokes, acute chest syndrome, priapism, hepatobilliary and liver disease, splenic infarction, life-threatening infections, renal disease, retinopathy, shortened lifespan

HbAS
(Sickle trait)

Heterozygous for sickle mutation and normal b-globin

HbA > HbS No anaemia and generally no other symptoms; rarely, haematuria, urinary tract infection and splenic infacts; very rarely (with extreme conditions, e.g. high altitude, extreme physical exertion, pneumonia) symptoms of SCA.
Normal life expectancy

HbSC
(Sickle, HbC disease)

Heterozygous for sickle mutation and C mutation (lysine at sixth position of b-globin chain). HbS can polymerise with HbC, but does so less avidly than with another HbS

HbS = HbC
Normal to slightly elevated HbF

Same constellation of symptoms as SCA, but significantly milder. Life expectancy 60–68 yearsb
HbS–b-Thal
(Sickle, b-Thalassaemia) 		Heterozygous for sickle mutation and one of b-thalassaemia mutations that causes decreased (b+-thalassaemia) or absent (b0-thalassaemia) normal b-globin HbS with (1) no HbA (b0) or (2) HbS > HbA (b+) Variable HbF and HbA2

Severity of clinical symptoms are inversely related to the amount of HbA and HbF made. Sb0-thalassaemia is clinically manifested like SCA; Sb+-thalassaemia is milder and can be as mild as sickle trait

HbS–HPFH
(SCA–Hereditary persistence of fetal haemoglobin)

Homozygous for sickle mutation with deletional or non-deletional mutations that increase HbF

HbS
HbF: 20–30%

No symptoms because HbF and HbS cannot polymerise

HbSE
(Sickle, HbE disease)

Heterozygous for sickle mutation and E mutation (lysine for glutamic acid at 26th position of b-globin chain). HbS can polymerise with HbE, but does so less avidly than with another HbS

HbS
HbE: 30% 		Mild anaemia, no symptoms. HbE does not polymerise
HbSD
(Sickle, HbD)

Heterozygous for sickle mutation and D mutation (glutamine for glutamic acid at position 121 of b-globin chain). HbS can polymerise with HbD but does so less avidly than with another HbSb

 HbS
HbD 		Mild anaemia, mild SCA symptoms: the mildest of the symptomatic SCD syndromesb unless HbS and HbD mutation on the same allele
HbSOArab
(Sickle, HbOArab)

Heterozygous for sickle mutation and O mutation (glutamic acid for lysine at position 121 of b-globin chain)c. HbS can polymerise with HbO but does so less avidly than with another HbS

 HbS
HbD 		Anaemia and SCA symptoms; indistinguishable from SCA
HbS–a-Thal
(SCA, a-Thalassaemia)

Homozygous for sickle mutation with mutations causing decreased (trait or a+-thalassaemia) or absent (a0-thalassaemia) a-globin chains

 HbS SCA symptoms, but milder. Symptoms are ameliorated because less HbS is formed, as a result of low a-globin availability; HbS concentration is thus decreased, reducing sicklingd

a Except where indicated otherwise, the information in this table was obtained from Refs 2 and 4.

b Ref. 183

c Refs 184, 185

d Ref. 33

Abbreviations: Hb, haemoglobin; SCA, sickle cell anaemia.

References cited in Table 1

2 Lukens, J. (2004) Abnormal hemoglobins, general principles. In Wintrobe’s Clinical Hematology (Greer, J.P. et al., eds), pp. 1247-1262, Lippincott Williams and Wilkins, Philadelphia, USA

4 Wang, W. (2004) Sickle cell anemia and other sickling syndromes. In Wintrobe’s Clinical Hematology (11th edn), (Greer, J.P. et al., eds), pp. 1263-1296, Lippincott Williams and Wilkins, Philadelphia, USA

33 Embury, S.H. (1989) Alpha thalassemia. A modifier of sickle cell disease. Ann N Y Acad Sci 565, 213-221, PubMed

183 Beutler, E. (2001) Disorders of hemoglobin structure: sickle cell anaemia and related abnormalities. In William’s Hematology (Beutler, E., Coller, B.S. and Litchman, M.A.K.T.J.S.U., eds), pp. McGraw-Hill, New York, USA

184 Baglioni, C. and Lehmann, H. (1962) Chemical heterogeneity of haemoglobin O. Nature 196, 229-232, PubMed

185 Wick, T.M. et al. (1987) Unusually large von Willebrand factor multimers increase adhesion of sickle erythrocytes to human endothelial cells under controlled flow. J Clin Invest 80, 905-910, PubMed

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