Hereditary Elliptocytosis - Genetic Prevalence

Genetic Prevalence

The incidence of hereditary elliptocytosis is hard to determine, as many sufferers of the milder forms of the disorder are asymptomatic and their condition never comes to medical attention. Around 90% of those with this disorder are thought to fall into the asymptomatic population. It is estimated that its incidence is between 3 and 5 per 10,000 in the USA, and that those of African and Mediterranean descent are of higher risk. Because it can confer resistance to malaria, some subtypes of hereditary elliptocytosis are significantly more prevalent in regions where malaria is endemic. For example, in equatorial Africa its incidence is estimated at 60-160 per 10,000, and in Malayan natives its incidence is 1500-2000 per 10,000. Almost all forms of hereditary elliptocytosis are autosomal dominant, and both sexes are therefore at equal risk of having the condition. The most important exception to this rule of autosomal dominance is for a subtype of hereditary elliptocytosis called hereditary pyropoikilocytosis (HPP), which is autosomal recessive.

There are three major forms of hereditary elliptocytosis: common hereditary elliptocytosis, spherocytic elliptocytosis and southeast Asian ovalocytosis.

Common hereditary elliptocytosis is the most common form of elliptocytosis, and the form most extensively researched. Even when looking only at this form of elliptocytosis, there is a high degree of variability in the clinical severity of its subtypes. A clinically significant haemolytic anaemia occurs only in 5-10% of sufferers, with a strong bias towards those with more severe subtypes of the disorder.

Southeast Asian ovalocytosis and spherocytic elliptocytosis are less common subtypes predominantly affecting those of south-east Asian and European ethnic groups, respectively.

The following categorisation of the disorder demonstrates its heterogeneity:

• Common hereditary elliptocytosis (in approximate order from least severe to most severe)
  • With asymptomatic carrier status - the individual has no symptoms of disease and diagnosis is only able to be made on blood film
  • With mild disease - the individual has no symptoms and a mild and compensated haemolytic anaemia
  • With sporadic haemolysis - the individual has a predilection towards haemolysis in the presence of particular comorbidities, including infections, and vitamin B deficiency
  • With neonatal poikilocytosis - during the first year of life only the individual has a symptomatic haemolytic anaemia with poikilocytosis
  • With chronic haemolysis - the individual has a moderate to severe symptomatic haemolytic anaemia (this subtype has variable penetrance in some pedigrees)
  • With homozygosity or compound heterozygosity - depending on the exact mutations involved, the individual may lie anywhere in the spectrum between having a mild haemolytic anaemia and having a life-threatening haemolytic anaemia with symptoms mimicking those of HPP (see below)
  • With pyropoikilocytosis (HPP) - the individual is typically of African descent and has a life-threateningly severe haemolytic anaemia with micropoikilocytosis (small and misshapen erythrocytes) that is compounded by a marked instability of erythrocytes in even mildly elevated temperatures (pyropoikilocytosis is often found in burns victims and is the term is commonly used in reference to such people)
• South-east Asian ovalocytosis (SAO) (also called stomatocytic elliptocytosis) - the individual is of South-East Asian descent (typically Malaysian, Indonesian, Melanesian, New Guinean or Filipino, has a mild haemolytic anaemia, and has increased resistance to malaria
• Spherocytic elliptocytosis (also called hereditary haemolytic ovalocytosis) - the individual is European descent and elliptocytes and spherocytes are simultaneously present in their blood