Hereditary Stomatocytosis

Signs and Symptoms:

The inheritance of hereditary stomatocytosis is autosomal dominant. 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. Ask for genetic
counselling to get a complete explanation

Overhydrated hereditary stomatocytosis (OHSt) onset occurs during the neonatal period or infancy
with hemolytic anemia that may require occasional blood transfusions. Splenomegaly or
hepatosplenomegaly are present. The disease course is marked by the usual complications of hemolytic
anemia (biliary lithiasis) and, remarkably, by a strong tendency for iron overload. In the majority of
cases, OHSt is caused by mutations in the RHAG gene (6p21-qter) encoding the Rh-associated
glycoprotein component of the Rh complex.

Dehydrated hereditary stomatocytosis (DHS) Most reported DHS cases are caused by gain-of-function
mutations in the gene PIEZO1 (16q24.3) which encodes part of a mechanosensitive ion channel. This
results in increased red cell membrane permeability for cations that consequently leads to cation
depletion, dehydration and shortened red cell survival. Rare atypical forms have been associated with
mutations in SLC4A1 (17q21.31), coding for the Band 3 anion transport protein, or KCNN4 (19q13.2)
which codes for the putative Gardos channel.

Diagnosis:

 One diagnosis is a blood test called Hemoglobin. This laboratory test is used to see if a person has
anything wrong with their red blood cells. It performs a complete blood count (CBC) and is able to
see if a person has any blood disorders or if a person is in need of a blood transfusion. This test tells
a physician if there is a problem with the number of red blood cells or if there is a problem with the
amount of time they remain viable. This is not the only form of diagnosis, as it only tells the
physician if there is a disorder.
 Another way to diagnose the disease in a lab test called pseudohyperkalaemia. This is used to
determine the amount of potassium in the patient’s plasma. Patient's usually present for this if they
have haemolysis, which is a breakdown in red blood cells.
 A third way to help diagnosis Hereditary Stomatocytosis is thrombosis after splenectomy. This is the
formation of a blood clot in the blood vessel, which stops or slows the flow of blood after the
removal of a spleen, which filters red blood cells.
 The last way to diagnosis Hereditary Stomatocytosis is perinatal ascites, which is a large build up of
fluid in the abdominal cavity.
Description:

Hereditary Stomatocytosis comprises two different diseases: the xerocytosis or dehydrated hereditary
stomatocytosis and the overhydrated hereditary stomatocytosis. Both are genetic disorders mainly due
to abnormality of red cell membrane permeability to monovalent cations (Na+ and K+) resulting in an
alteration in the red blood cell water content. Typical red blood cells known as stomatocytes (mouth
featured cells) appear in blood smear examination. The clinical manifestation can vary from
asymptomatic to severe haemolytic anaemia.

The main function of the red blood cell is to carry oxygen around the body. Osmosis, the process where
the cell would swell and burst takes place inside the cell. "The cell counters this tendency by
manipulating the flow of the salt atoms, sodium and potassium. The cell has a 'pump', which forces
sodium out of the cell and potassium in, and in normal cells the action of this pump is balanced by a
process called 'the passive leak'." In Hereditary Stomatocytosis, the leak increases so much that the cell
cannot hold all the salt and water, so it bursts and creates the cells to have different shapes. Regarding
hereditary stomatocytosis, both the dehydrated and overhydrated forms exhibit a cation leak to the
univalent cations Na+ and K+ that results in altered intracellular cation content and cell volume
alterations.

Overhydrated hereditary stomatocytosis (OHSt) is a disorder of red cell membrane permeability to

monovalent cations and is characterized clinically by hemolytic anemia. OHSt is very rare with only
seven cases described in the literature so far. The distinctive feature of overhydrated hereditary
stomatocytosis is increased cell hydration with resultant increase in mean corpuscular volume, a
decreased mean corpuscular hemoglobin concentration, and an increased osmotic fragility.

Dehydrated hereditary stomatocytosis (DHS) is a rare hemolytic anemia characterized by a decreased

red cell osmotic fragility due to a defect in cation permeability, resulting in red cell dehydration and mild
to moderate compensated hemolysis. Pseudohyperkalemia (loss of potassium ions from red cells on
storage at room temperature) is sometimes observed. The prevalence of DHS is unknown but to date,
about 20 families with DHS have been described in the literature. The distinctive feature of dehydrated
hereditary stomatocytosis is cell dehydration, with a resultant increase in mean corpuscular hemoglobin
concentration and decreased osmotic resistance.
Effects:

Some clinical problems in Hereditary Stomatocytosis are mild enough to let the patient live a normal life.
Although Gallstones can be a problem, that can be easily fixed with a surgery. A patient who has
Hemolytic anemia may face a problem where they encounter a temporary anemic period when there is
an infection. If this occurs a transfusion may be needed for a little while. If a person with Hereditary
Stomatocytosis removes their spleen, they need to make sure that they do not show issues later in life.
These issues are blood clots, abdominal pain, chest pain, breathing with difficulty or blood clotting in the
superficial veins. If this occurs the patient needs to have Anticoagultant treatment. Anticoagulatant is a
blood thinner that makes you bleed easily. Neonates with overhydrated hereditary stomatocytosis
(OHSt) or dehydrated hereditary stomatocytosis (DHSt) may require phototherapy, simple blood
transfusions, and, occasionally, exchange transfusions for treatment of anemia and hyperbilirubinemia.

Most hereditary stomatocytoses are quite mild anemias and the patients can lead a normal life.
Gallstones can cause trouble but are usually easy to deal with surgically. Any patient with haemolytic
anemia may be subject to 'crises' in which they become severely, but temporarily, anemic at times of
infection. Transfusion may be required for a few days.

Four special problems affect stomatocytosis patients. First, if the spleen is removed (a procedure which
helps a great deal in spherocytosis, from which the stomatocytoses can be difficult to distinguish), then
in later life problems with excessive blood clotting may arise. This can manifest as abdominal pain, chest
pain, breathlessness or episodes of clotting in the superficial veins in the skin. Anticoagulant treatment
should be given, often on a long term basis.

Secondly, because the membrane is leaky to sodium and potassium, blood samples which are taken for
measurement of the concentration of these substances in the plasma can be misleading. This effect
does not happen in all families.

Thirdly, in some families, it has been observed that new-born babies can show an excess of fluid in some
of the compartments of the body. The cause of this is far from clear, but it seems to simply improve as
the infants mature. Presumably the abnormal gene is expressed at this early stage of life and as a result
the reabsorption of fluid from the tissues and the ascitic cavity is impaired. The membrane may 'leak' as
in the red cell.

Fourthly, in some families overloading with iron has been found. This can cause damage to the liver and
heart
References:

 http://www.enerca.org/anaemias/pubmed/58/hereditary-stomatocytosis
 http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=3202
 http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=3203
 http://hereditarystomatocytosiskw.weebly.com/
 http://www.hematologyandoncology.net/index.php/archives/september-2014/the-red-cell-
membrane-part-2-disorders-of-the-red-cell-membrane/
 http://www.ucl.ac.uk/~rmhagst/stomatocytosis.htm