Hemoglobin constant spring: Hemoglobin synthesis in heterozygous and homozygous states

Pongsamart, Sunanta; Pootrakul, S.; Wasi, P; Na-Nakorn, S

doi:10.1016/0006-291x(75)90374-5

Cited by 15 publications

(3 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This condition causes mild haemolytic anaemia with a baseline Hb range of 9-11 g/dL, icteric sclera and mild hepatosplenomegaly. [17][18][19][20][21] A recent study of patients with HbH-CS has provided insight into the pathophysiology of this abnormal a globin variant. The attachment of partially oxidised a CS chains on the red cell membrane and its cytoskeleton might give rise to increased membrane rigidity and stability compared with the normal red cell membrane.…”

Section: Discussionmentioning

confidence: 99%

Acute haemolytic crisis in a Thai patient with homozygous haemoglobin Constant Spring (Hb CS/CS): a case report

Viprakasit

Veerakul

Sanpakit

et al. 2004

Annals of Tropical Paediatrics

View full text Add to dashboard Cite

Acute haemolysis associated with mild upper respiratory tract infection was observed in a Thai boy who presented with a rapid decline in haemoglobin (Hb) levels, haemoglobinuria and evidence of intravascular haemolysis. Several possible causes giving rise to such a condition were excluded including G6PD deficiency, which is extremely common in Thailand. Subsequent haematological and molecular analyses demonstrated that the patient was homozygous for Hb Constant Spring (Hb CS/CS), an a globin haemoglobinopathy. It has been shown previously that patients with homozygous Hb CS had mild haemolytic anaemia secondary to an accumulation of alpha(CS) chains, which are toxic to red blood cell membrane cytoskeletons. Increased body temperature might induce more precipitation of this a globin variant. This report highlights the importance of Hb CS/CS as a potential predisposing cause of acute haemolysis in children that might be aggravated by acute bacterial or viral infections. This is particularly relevant for patients of Southeast Asian descent where this abnormal haemoglobin is highly prevalent.

show abstract

Section: Discussionmentioning

confidence: 99%

Acute haemolytic crisis in a Thai patient with homozygous haemoglobin Constant Spring (Hb CS/CS): a case report

Viprakasit

Veerakul

Sanpakit

et al. 2004

Annals of Tropical Paediatrics

View full text Add to dashboard Cite

show abstract

“…Both heterozygotes (aa/a a) and homozygotes (a/aaCSa) have been reported to show a/fl globin chain synthesis ratios > 1, rather than the expected deficit of a-chain production (5,6). Furthermore, since the ccs-gene is associated with a very low output of a-globin chains, homozygotes should have the same clinical 1.…”

Section: Introductionmentioning

confidence: 99%

Hematologic and biosynthetic studies in homozygous hemoglobin Constant Spring.

Derry¹,

Wood²,

Pippard³

et al. 1984

J. Clin. Invest.

View full text Add to dashboard Cite

Abstract. The elongated a-globin chains of hemoglobin Constant Spring (acs chain of HbCS) are produced in low amounts such that the acs-gene acts as a form of a-thalassemia; yet in the homozygous state the pathophysiological effects of this mutant are more severe than in the corresponding conditions that result from aglobin gene deletions. In studies designed to examine this discrepancy, we have demonstrated that a significant proportion of red cells produced in an HbCS homozygote has a much reduced red cell life span. Contrary to previous reports, we have been able to demonstrate the expected deficit in a-chain production in this condition and have shown that both the cessation of globin chain synthesis in vitro and the destruction of the excess 3-chains occur unusually rapidly. Comparison with various deletion forms of a-thalassemia suggests that, in terms of intracellular globin chain precipitates and free ,8-chain pool, homozygous HbCS red cells more closely resemble those of HbH disease, with three ofthe four a-genes inactivated, than they do the more comparable a-thalassemia carriers with only two genes deleted.

show abstract

“…, although there is some disagreement about the stability of acs chains (Pongsamart et al, 1975;Pootrakul et al, 19 76). Since the ratio of xcS: a* chains synthesized in bone marrow is higher than in peripheral blood (Kan et al, 19 74;Weatherall & Clegg, 1975), it has been postulated that the low level ofHb CS in the peripheral blood could be due to an unstable mRNA rather than unstable protein (Kan et al, 1974;Clegg & Weatherall, 1974;Weatherall & Clegg, 1975;Pootrakul et al, 1976).…”

mentioning

confidence: 99%

Haemoglobin Constant Spring has an unstable α chain messenger RNA

Hunt¹,

Higgs²,

Winichagoon³

et al. 1982

Br J Haematol

View full text Add to dashboard Cite

Haemoglobin Constant Spring (Hb CS) is a variant with an elongated alpha-chain associated with an alpha + thalassaemia phenotype. The amount of alpha mRNA relative to beta mRNA in reticulocytes was reduced in carriers of Hb CS by an amount equivalent to the reduction observed in carriers of alpha + thalassaemia. In a patient with Hb CS-H disease there was greater alpha/beta mRNA ratio in bone marrow nuclear RNA than in the peripheral blood. Furthermore, all the alpha mRNA in the patient's peripheral blood was derived from the alpha 1 (alpha A) gene. The data suggest that alpha CS mRNA is unstable and degraded in the cytoplasm. This instability may be due to destabilization of a specific sequence in the 3' non-coding region during translation.

show abstract

Hemoglobin constant spring: Hemoglobin synthesis in heterozygous and homozygous states

Cited by 15 publications

References 14 publications

Acute haemolytic crisis in a Thai patient with homozygous haemoglobin Constant Spring (Hb CS/CS): a case report

Acute haemolytic crisis in a Thai patient with homozygous haemoglobin Constant Spring (Hb CS/CS): a case report

Hematologic and biosynthetic studies in homozygous hemoglobin Constant Spring.

Haemoglobin Constant Spring has an unstable α chain messenger RNA

Contact Info

Product

Resources

About