Hereditary Elliptocytosis: A Seminar Report On

A SEMINAR REPORT ON
Hereditary elliptocytosis
Submitted By
Mrs. Sunita
Examination No.:-
Roll No.:-
Under the Guidance of:

Mr. Dhamak sir
Bachelor of Pharmacy
Pravar Rural Education Society's College of Pharmacy
Sinnar, Nashik, Maharashtra 422103
INTRODUCTION
Hereditary elliptocytosis, also known as ovalocytosis, is an inherited blood

disorder in which an abnormally large number of the patient's erythrocytes (i.e. red
blood cells) are elliptical rather than the typical biconcave disc shape. Such
morphologically distinctive erythrocytes are sometimes referred to
as elliptocytes or ovalocytes. It is one of many red-cell membrane defects. In its
severe forms, this disorder predisposes to haemolytic anaemia. Although
pathological in humans, elliptocytosis is normal in camelids.
Hereditary spherocytosis and elliptocytosis are the two most common
inherited red cell membrane disorders resulting from mutations in genes encoding
various red cell membrane and skeletal proteins. Red cell membrane, a composite
structure composed of lipid bilayer linked to spectrin-based membrane skeleton is
responsible for the unique features of flexibility and mechanical stability of the
cell. Defects in various proteins involved in linking the lipid bilayer to membrane
skeleton result in loss in membrane cohesion leading to surface area loss and
hereditary spherocytosis while defects in proteins involved in lateral interactions of
the spectrin-based skeleton lead to decreased mechanical stability, membrane
fragmentation and hereditary elliptocytosis. The disease severity is primarily
dependent on the extent of membrane surface area loss. Both these diseases can be
readily diagnosed by various laboratory approaches that include red blood cell
cytology, flow cytometry, ektacytometry, electrophoresis of the red cell membrane
proteins, and mutational analysis of gene encoding red cell membrane proteins.
A number of inherited red cell disorders due to altered membrane function
have been identified. These include hereditary spherocytosis (HS), hereditary
elliptocytosis (HE), hereditary ovalocytosis (SAO), and hereditary stomatocytosis
(HSt). HS and HE16 are the most common red cell membrane disorders in the
world with a prevalence of 1 out of 2000 affected cases in North America and
Northern European countries and are likely to be even higher due to under
diagnosis of asymptomatic forms. Both diseases result from defects in genes
encoding various membrane and skeletal proteins that play a role in regulating
membrane cohesion and membrane mechanical stability.16 In both HS and HE,
red cell life span is shortened as result of splenic sequestration of red cells. The
abnormal red cells with decreased membrane surface area and increased sphericity
are trapped in the billroth canals in the spleen and phagocytozed by the splenic
reticulo-endothelial system resulting in regenerative hemolytic anemia,
splenomegaly, and ictera with increased free bilirubin level. The severity of the
disease depends on the extent of surface area loss and ranges from asymptomatic
forms to severe neonatal or prenatal forms responsible for rare hydrops fetalis
cases requiring transfusion in utero. In this review, we will summarize the
substantial progress that has been made in our understanding of i) structural
organization of the red cell membrane including comprehensive characterization of
a large number of membrane proteins, ii) structural basis for the interactions
between various membrane and skeletal proteins and how defects in these
interactions due to mutations in genes encoding the various proteins lead to
defective membrane function, and iii) appropriate methodologies including genetic
analy
The following categorization of the disorder demonstrates its heterogeneity:
Common hereditary elliptocytosis (in approximate order from least severe to
most severe)
With asymptomatic carrier status - individuals have no symptoms of disease
and diagnosis is only able to be made on blood film
With mild disease - individuals have no symptoms, with a mild and
compensated haemolytic anaemia
With sporadic haemolysis - individuals are at risk of haemolysis in the
presence of particular comorbidities, including infections, and vitamin
B12 deficiency
With neonatal poikilocytosis - individuals have a symptomatic haemolytic
anaemia with poikilocytosis that resolves in the first year of life
With chronic haemolysis - 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, individuals 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
With pyropoikilocytosis (HPP) - individuals are typically of African descent
and have 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) - individuals are of South-East Asian descent
(typically Malaysian, Indonesian, Melanesian, New Guinean or Filipino,
have a mild haemolytic anaemia, and has increased resistance to malaria
Spherocytic elliptocytosis (also called hereditary haemolytic ovalocytosis) -
individuals are of European descent and elliptocytes and spherocytes are
simultaneously present in their blood
HISTORY OF DIABETES INSIPIDUS
Elliptocytosis was first described in 1904, and was first recognised as
a hereditary condition in 1932.[2] More recently it has become clear that the
severity of the condition is highly variable and there is much
genetic variability amongst those affected
Hereditary elliptocytosis (HE) is a heterogeneous group of disorders that
shares the common feature of generally having more than 25% elliptical red blood
cells (RBCs). Because specific molecular lesions are not necessarily correlated
with clinical manifestations, a morphologic classification has been devised. The
three commonly identified morphologic variants include common HE, spherocytic
elliptocytosis, and Southeast Asian ovalocytosis (SAO, also known as stomatocytic
elliptocytosis). Common HE can be further subcategorized on the basis of clinical
features.
Hereditary elliptocytosis (HE) encompasses inherited disorders of
erythrocytes that have the common feature of elliptical RBCs on morphologic
examination and shortened RBC survival. These disorders are clinically,
genetically, and biochemically heterogeneous. HE is due to defects in either the
structure or quantity of the cytoskeletal proteins responsible for maintaining the
biconcave morphology of RBCs. Mutations in either alpha- and beta-spectrin are
most commonly responsible, but mutations in other cytoskeletal proteins (band 4.1
and glycophorin) are also described. [2] Most of these disorders are clinically
silent, with only some forms associated with clinically significant hemolysis.
The mode of inheritance is autosomal dominant, except for hereditary
pyropoikilocytosis (HPP) which is autosomal recessive. Instances of spontaneous
mutations are rare.
CAUSES AND SYMPTOMS
Causes:
HE arises from a variety of structural defects in proteins unique to the RBC
membrane. Mutations involving the membrane components spectrin, ankyrin, or
protein band 4.1 lead to defective formation of the RBC membrane cytoskeleton.
Thus, normally flexible erythrocytes are rendered more rigid. During transit
through the spleen, the anoxic, hypoxic, and hypocalcemic microenvironment
leads to an increase in RBC inflexibility. This leads to delayed transit times and an
increased loss of membrane by RBC by splenocytes, which in turn lead to further
rigidity and decreased RBC survival time. The elliptic shape is acquired in the
circulation and arises from the interaction of membrane molecular defects and
splenic conditioning. Reticulocytes from patients with HE are normal in
appearance. The clinical relevance of HE is determined by the severity of disease
and its manifestation in the patient. Mild disease, with asymptomatic anemia
without significant jaundice, gallstone formation, or symptomatic splenomegaly,
requires no treatment. Preventive measures, such as avoidance of dehydration,
early treatment of infections, and timely vaccination should suffice. 10% of
affected patients have more severe forms of HE, which manifest as hemolytic
crises leading to anemia, jaundice, and, over time, cholelithiasis.
Symptoms
These patients may respond to splenectomy, but vaccination and antibiotic
prophylaxis against encapsulated organisms should be provided prior to
splenectomy. Patients demonstrating hemolytic HE with spherocytes have the most
severe manifestations of the disease and may represent those heterozygous for HE
and HS or those homozygous for HE. These patients should be treated
aggressively, as one would treat a patient with HS, with transfusions, vaccinations,
antibiotic therapy for infections, and splenectomy after 5 years of age. The only
curative therapy for those not responding to these supportive measures is
allogeneic marrow transplantation, but few patients have been treated in this way.
Genetic counseling is an effective means of disease prevention.
INVESTIGATIONS AND TREATMENT
Investigations:
The diagnosis of hereditary elliptocytosis is usually made by coupling a family
history of the condition with an appropriate clinical presentation and confirmation
on a blood smear. In general it requires that at least 25% of erythrocytes in the
specimen are abnormally elliptical in shape, though the observed percentage of
elliptocytes can be 100%. This is in contrast to the rest of the population, in which
it is common for up to 15% of erythrocytes to be elliptical.[12]
If some doubt remains regarding the diagnosis, definitive diagnosis can
involve osmotic fragility testing, an autohaemolysis test, and direct protein
assaying by gel electrophoresis.
Treatment:
The vast majority of those with hereditary elliptocytosis require no treatment
whatsoever. They have a mildly increased risk of developing gallstones, which is
treated surgically with a cholecystectomy if pain becomes problematic. This risk is
relative to the severity of the disease.
Folate helps to reduce the extent of haemolysis in those with significant
haemolysis due to hereditary elliptocytosis.
Because the spleen breaks down old and worn-out blood cells, those individuals
with more severe forms of hereditary elliptocytosis can have splenomegaly.
Symptoms of splenomegaly can include:
Vague, poorly localised abdominal pain
Fatigue and dyspnoea
Growth failure
Leg ulcers
Gallstones.
Removal of the spleen (splenectomy) is effective in reducing the severity of
these complications, but is associated with an increased risk of overwhelming
bacterial septicaemia, and is only performed on those with significant
complications. Because many neonates with severe elliptocytosis progress to have
only a mild disease, and because this age group is particularly susceptible
to pneumococcal infections, a splenectomy is only performed on those under 5
years old when it is absolutely necessary.
CONCLUSION
REFERENCES
1. Harper SL, Sriswasdi S, Tang HY, Gaetani M, Gallagher PG, Speicher DW.
The common hereditary elliptocytosis-associated a-spectrin L260P mutation
perturbs erythrocyte membranes by stabilizing spectrin in the closed dimer
conformation. Blood. 2013 Aug 23 2.
2. Gallagher PG. Hemolytic anemias In: Goldman L, Schafer AI,
eds. Goldman's Cecil Medicine. 25th ed. Philadelphia, PA: Elsevier Saunders;
2016:chap 161
2. www.wikipedia.com
3. www.researcgate.com

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A SEMINAR REPORT ON

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Hereditary elliptocytosis, also known as ovalocytosis, is an inherited blood

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