The paradox of hemoglobin SC disease.
Homozygous HbC gene results only in mild hemolytic anemia. In HbSC disease red cells contain equal levels of HbS and HbC. It is a paradox that HbSC exhibit a moderately severe phenotype in spite of being a mixture of HbS trait and HbC trait, neither of which has significant pathology. Why does the combination of these two Hbs result in a serious disease? The short answer is that HbC enhances, by dehydrating the SC red cell, the pathogenic properties of HbS, resulting in a clinically significant disorder, but somewhat milder that sickle cell anemia (SCA). Nevertheless, retinnitis proliferans, osteonecrosis, and acute chest syndrome have equal or higher incidence in HbSC disease compared to SCA. This pathogenic trick is accomplished by HbC inducing, by mechanisms not fully understood, an increase in the activity of K:Cl cotransport that induces the lost of K(+) and consequently of intracellular water. This event creates a sufficient increase of MCHC, so that the lower levels of HbS found in SC red cells can polymerize rapidly and effectively. This situation offers a unique opportunity: if we could inhibit the effect of HbC on K(+) transport we can cure the disease.
Nagel
Ronald L
RL
Division of Hematology, Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, The Bronx, NY, USA.
Fabry
Mary E
ME
Steinberg
Martin H
MH
D000755:Anemia, Sickle Cell / Q000097:blood / Q000235:genetics / Q000503:physiopathology; D003460:Crystallization; D004913:Erythrocytes, Abnormal / Q000378:metabolism / Q000648:ultrastructure; D006444:Hemoglobin C / Q000737:chemistry / Q000235:genetics; D006450:Hemoglobin SC Disease / Q000097:blood* / Q000235:genetics / Q000503:physiopathology*; D006451:Hemoglobin, Sickle / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008855:Microscopy, Electron, Scanning; D010641:Phenotype; D011188:Potassium / Q000378:metabolism
D006451:Hemoglobin, Sickle; D006444:Hemoglobin C; D011188:Potassium