A person may also be a carrier of the disease and show no signs or symptoms of the disease. Late complications may result in the development of pigmented gallstones, which is secondary to the detritus of the broken-down blood cells (unconjugated or indirect bilirubin) accumulating within the gallbladder. Also, patients who are heterozygous for a hemochromatosis gene may exhibit iron overload, despite the hemochromatosis genes being recessive. In chronic patients, an infection or other illness can cause an increase in the destruction of red blood cells, resulting in the appearance of acute symptoms, a hemolytic crisis. On a blood smear, Howell-Jolly bodies may be seen within red blood cells. Primary treatment for patients with symptomatic HS has been total splenectomy, which eliminates the hemolytic process, allowing normal hemoglobin, reticulocyte and bilirubin levels. The resultant asplenic patient is susceptible to encapsulated bacterial infection, and prevented with vaccination. If other symptoms, such as abdominal pain persist, the removal of the gallbladder may be warranted for symptomatic cholelithiasis. Epidemiology
Hereditary spherocytosis is the heritable hemolytic disorder, affecting 1 in 2,000 people of Northern European ancestry. According to Harrisons Principles of Internal Medicine, the frequency is at least 1 in 5,000 within the United States of America. While HS is most commonly (though not exclusively) found in Northern European and Japanese families, an estimated 25% of cases are due to spontaneous mutations.
Etiology
Hereditary spherocytosis is an erythrocytic disorder of that affects the following red cell membrane proteins in a congenital fashion:

Spectrin (alpha and beta)
Ankyrin
Band-3 Protein
Protein-4.2
Lesser proteins of significanceHereditary spherocytosis can be an autosomal recessive or autosomal dominant trait. The autosomal recessive inheritance pattern accounts for close to 25% of the clinical cases. The autosomal dominant inheritance patter accounts for over 75% of the clinical cases. Many positive individuals will not present clinically, thus the etiologic data may be artificially skewed towards the more prominent dominant forms. These dominant forms tend to leave a family history that  yields generational splenectomies and black gallstones cholelithiasis. Lastly, an estimated 25% of cases are due to spontaneous mutations. Pathophysiology
Causative Genetic Mutations and Phenotypic Expressions
Hereditary spherocytosis is caused by a variety of molecular defects in the genes that code for the red blood cell proteins spectrin (alpha and beta), ankyrin, band 3 protein, protein 4.2, and other red blood cell membrane proteins:
*Online Mendelian Inheritance in Man (OMIM). The Alpha-1 refers the Alpha-1 Subunit of the Spectrin protein. The Beta refers the Beta Subunit of the Spectrin protein. These genetic mutations are acted upon and executed by erythrocyte progenitor cells within the bone marrow, where red blood cells are normally produced in the non-pathological state (see Extramedullary Hematopoiesis for pathological production outside of the bone marrow). Pathophysiology of Mutated Erythrocytic Membrane Proteins
These proteins are necessary to maintain the normal shape of a red blood cell, which is a biconcave disk.