Elliptocytosis and Spherocytosis
Elliptocytosis (EC) and Spherocytosis (SC) are two diseases that create improperly shaped red blood cells; in EC they are elliptical and in SC spherical. These misshapen blood cells are much more fragile than wild type blood cells and are easily lysed. This creates a faster turnover of rbc's in the affected individual which, if not countered by increased blood production, blood transfusions, or alleviation of the condition, can lead to a lack of oxygen in the blood (anemia or aplastic crisis in the severe case).
There are several different ways to determine if an individual is affected by either of these diseases. The simplest of these methods involves visualization of the blood cells on a slide and comparison to wild type. Also, if too much hemoglobin is present in a blood sample (more than 35% vs. around 30%), then EC or SC may be the cause. To ensure that EC or SC are the cause, a Coomb's test is done in which an autoimmune attack can be ruled out as a possible cause. After this another test is done which determines whether EC or SC is the culprit.
EC/SC leads to a number of symptoms besides anemia, but these are not always serious. In most cases an enlarged spleen is the primary symptom, for which no treatment is usually given (as the condition is not overly detrimental to the patient's health). Also a possibility, and a more serious one, is that folic acid from hemolytic anemia is present. This can also be accompanied by corcus steroids from aplastic crisis or hemolytic anemia. In cases such as these two treatment options are available. The first option is the use of blood transfusions, which alleviates the symptoms as new, longer lasting red blood cells are added. However, repeated transfusions are necessary and in this instance the disease itself is not directly dealt with. The second treatment method involves the removal of the spleen. This prevents the altered blood cells from building up in the spleen and reduces their lysis, but without the spleen individuals are subject to attack by infectious agents which could lead to noscomial infections or septic shock. An intermediate option is also available whereby only a partial spleenectomy is performed (this usually avoids septic shock).
These diseases are caused by failures in any one of four peripheral proteins. The proteins involved, ankryn, spectrin, Protein Three, and Protein 4.1, are on the inside of the outer membrane on the red blood cell. There they form a cytoskeleton which provides structure to the red blood cells. Because of this, a loss of function in any of the proteins cripples the red blood cells' ability to hold shape, and thus oxygen, due to the disruption of the complex cytoskeletal structure. Not all mutations are equally as devastating, however. Lower amounts of spectrin and Protein 4.1, for instance, cause EC/SC to be more severe.
Due to the interlinking of the proteins, many different forms are known. Mutations can occur that are autosomal dominant (most of the cases) or autosomal recessive (25% of the cases and more debilitating). The ability to be either dominant or recessive is a reflection of the interlocking nature of the proteins. Any mutation that hinders the connection between the proteins hinders all four, while any mutation that causes the loss of function of just one part of one protein may be compensated for (to some extent) by the others.
Generally then, EC and SC are diseases that have very well defined genetic natures (unfortunately space does not permit this discussion here). They are caused by a variety of different mutations at different loci that cause widely differing symptoms. The diseases are readily detected, and while treatment is generally not necessary it is difficult in those instances where it is required.