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At a glance

Hereditary spherocytosis is clinically characterized by anemia, jaundice, splenomegaly, and generalized fatigue. Most cases are detected soon after birth. However, it can manifest itself at the age of 4 or 5 years. It is a membrane defect within red blood cells (RBCs) resulting in a shortened survival time. The red cells have low amounts of lipid within the bilayer membrane that lead to an abnormally small amount of surface area that causes them to change their and become spherocytic. It affects vascular flow, resulting in hemolysis. It is caused by an inherited metabolic defect. There is no cure for this medical condition and the current management option is splenectomy (except for mild condition). Post-splenectomy risk includes sepsis and will require antibiotics or immunization to limit possible infection to streptococcus pneumoniae, meningococcus, and influenza.

Synonyms

Congenital Spherocytic Anemia; Minkowski-Chauffard Syndrome; Spherocytosis.

History

It was first described in 1871.

Nature

Hemolytic anemia caused by RBC membrane defect. Although a spectrin deficiency is seen in most hereditary spherocytosis patients, the principal defect is an abnormality of the RBC membrane protein ankyrin.

Incidence

It is the most common cause of inherited hemolysis in the Europe and North America within the Caucasian population, with an incidence of 1 in 5,000 births. Its incidence is more frequent in white populations originating from areas around the Mediterranean Sea. The prevalence of hereditary spherocytosis in people of other ethnic backgrounds is unknown, but it is much less common.

Classification

The severity of the signs and symptoms of the disease defines the four forms of hereditary spherocytosis. They are known as the mild, moderate, moderate/severe, and severe forms. It is estimated that 20 to 30% of people with hereditary spherocytosis have the mild form, 60 to 70% have the moderate form, 10% have the moderate/severe form, and 3 to 5% have the severe form.

Genetic inheritance

Autosomal dominant in most cases, but autosomal recessive forms exist (spectrin deficiency). Four subsets can be defined by the protein defect: (1) partial spectrin deficiency (mutations of alpha-spectrin are associated with recessive forms, whereas mutations of beta-spectrin produce autosomal dominant forms); (2) combined partial spectrin/ankyrin deficiency; (3) partial band 3 protein deficiency; and (4) protein 4.2 deficiency.

Pathophysiology

The protein abnormality causes defects in vertical stabilization of the phospholipid bilayer of the red cell membrane, which causes a separation of the spectrin-phospholipid bilayer. As a consequence, portions of the phospholipid bilayer form vesicles and thus are lost from the RBC surface—the surface area is decreased and spherocytes are formed. These abnormal RBCs are retained in the spleen and destroyed, leading to anemia.

Diagnosis

Based on clinical signs ...

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