98864, 98865, 286
OMIM code: 109270, 130600, 141700, 166900, 166910, 179650, 225450, 235370, 266140, 611804
ICD-10 code: D58.1
Include: Common, Autosomal dominant, Homozygous
Group: Congenital Red Cell Membrane defects
Hereditary elliptocytosis and hereditary pyropoikilocytosis are two variant forms of the same disease and differ in their severity and frequency. Both are genetic disorders affecting the red blood cell membrane resulting in decreased red cell deformability and mechanical stability, premature removal from blood circulation, and haemolytic anaemia of variable degree.
- What causes the disease and how common is it?
Hereditary elliptocytosis is a genetic disease. It is due to mutations in some of the proteins of the membrane skeletal network responsible for the stability of the red blood cell membrane (spectrin, protein 4.1 and glycophorin C). The defect of any of these proteins results in a decreased membrane mechanical stability leading to membrane fragmentation and producing an elliptocyte-shaped red blood cells also known as elliptocytes. Hereditary piropoikilocytosis is the severe form of hereditary elliptocytosis and appears when the network weakening is excessive, in these cases red blood cells undergo severe deformations, mimicking red cell fragmentation due to exposure to heat. Hereditary elliptocytosis has been reported world-wide showing an estimated frequency that ranges from 1:1000 to 1:4000. However, this prevalence could be higher since mild/asymptomatic forms can easily be not detected. Hereditary elliptocytosis is particularly common in black Africans and individuals of Mediterranean descent. Hereditary piropoikilocytosis is a very rare condition and only a limited number of families have been reported in Europe.
- What are the most frequent symptoms if I have the disease?
Typical hereditary elliptocytosis affected individuals present a very mild disease, even asymptomatic in some cases, that is discovered fortuitously on a blood smear examination. However, some patients exhibit haemolytic anaemia that ranges from mild to severe, jaundice (yellow colour of the eyes or even skin) and splenomegaly (spleen enlargement). The severe cases of haemolytic anaemia correspond to hereditary piropoikilocytosis. Hereditary elliptocytosis may be more clinically evident during the neonatal period but the manifestations decline after 4 months to 2 years of age to a mild common hereditary elliptocytosis. In hereditary piropoikilocytosis these manifestations remain, although more moderate, during the adult period.
- Which treatment must I follow if I have the disease?
Most cases of hereditary elliptocytosis are asymptomatic and do not require treatment. 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 in the most 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. Splenectomy should be considered only for severe forms of elliptocytosis and after 5 years of age. In hereditary piropoikilocytosis, splenectomy reduces but does not eliminate haemolysis completely. Regular follow-up for monitoring gallstones and iron overload should always be considered.
- What is the risk of passing the condition on to my children?
The transmission of hereditary elliptocytosis is autosomal dominant and autosomal recessive for hereditary piropoikilocytosis. 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. Ask for genetic counselling to get a complete explanation.