Hereditary Spherocytosis is a genetic disorder affecting the red blood cell membrane resulting in decreased red cell deformability, premature removal from blood circulation, and haemolytic anaemia of variable degree. Accordingly, the disease severity is classified in four categories: asymptomatic state, mild, moderate and severe.
Hereditary spherocytosis is a genetic disease. It is due to mutations in some of the proteins responsible for the stability of the red blood cell membrane (ankyrin, alpha and beta spectrin, band 3 and protein 4.2). The defect of any of these proteins leads to a loss of membrane and cellular content resulting in a spherical red blood cell also known as spherocyte. These spherocytes are more likely to haemolyse (burst) in the blood circulation or to be arrested in the spleen. Hereditary spherocytosis has been reported world-wide but it is particularly common in individuals of northern European ancestry. Its prevalence is estimated to be 1:2000 based on studies performed in blood donors. However, this prevalence could be higher since mild/asymptomatic forms can easily be not detected.
Diagnosis is often made in childhood or adolescence, although asymptomatic and mild forms may be identified in adult age and also in the elderly. In some cases anaemia becomes evident only in concomitance of infection diseases or during pregnancy. Most patients developed neonatal jaundice, although anaemia is not evident in some of them at that time point. Tipical hereditary spherocytosis patients present with haemolytic anaemia (pallor), jaundice (yellow color of the eyes or even skin), splenomegaly (spleen enlargement), and reticulocytosis (increase number of immature red blood cells). Gallstones are common leading to variable grades of cholelythiasis. Most of the patients have mild hereditary spherocytosis and up to 20-30% have a purely compensated hemolysis due to a balance between reticulocyte production and cell destruction. Severe cases may require repeated blood transfusions.
The treatment of red cell membrane defects is based on supportive measures: folate therapy is recommended in mild to severe forms of haemolytic anaemia, and red cell transfusions may be required only in severe cases, particularly in the first years of life, during aplastic crisis, infections, and pregnancy. Chelating therapy may be required to reduce iron overload due to periodical red cell transfusions. Regular follow-up for monitoring gallstones and iron overload should always be considered. Splenectomy is indicated in severe hereditary spherocytosis and in moderated to severe cases with significant anaemia and gallstone complications. Splenectomy should not be performed in cases of mild hereditary spherocytosis except in specific cases. Not all cases undergoing cholecystectomy should undergo splenectomy. Expert evaluation is expected in order to avoid unnecessary spleen resections. Since hereditary stomatocytosis, in which splenectomy is completely contraindicated, is easily misdiagnosed as hereditary spherocytosis, a differential diagnosis must be assured by high specialized laboratory methodologies before the surgery.
The transmission is autosomal dominant in 75% of cases and autosomal recessive in the remaining 25%. Autosomal dominat pattern: Only one copy of a mutated gene, from the mother or from the father, is needed to develop the disease. In these cases, the mother or the father is affected by the disease having one mutated gene. The couple has a 50 percent probability of having a child affected by the disease at each pregnancy. The probability of having a healthy child with no mutated gene is also 50 percent at each pregnancy. Autosomal recessive pattern: Two copies of a mutated gene, one from the mother and one from the father, are needed to develop the disease. In these cases, mother and father are healthy carriers for one mutated gene each one and they have a 25 percent probability of having a child affected by the disease at each pregnancy. The probability of having a child who is a healthy carrier, like the parents, is 50 percent at each pregnancy, and the probability that a child is not a carrier of a mutated gene neither affected by the disease is 25 percent. De novo mutations and low expression mutations have been also described to be present at a significant frequency altering the inheritance patterns explained above. Ask for genetic counselling to get a complete explanation.