Sickle Cell Anemia

What is Sickle Cell Anemia?

Sickle cell disease is an inherited

disorder that affects red blood cells.

Sickle Cell Anemia is a genetic disorder

that slightly alters the structure of

hemoglobin, the oxygen carrying protein

in red blood cells. This modefiedfied

hemoglobin, when not carrying oxygen,

tends to clump with other deoxygenated

hemoglobin and causing blood to cut

throughout the body.

Who Is At Risk for Sickle Cell Anemia?

Sickle cell disease affects more

than 72,000 Americans.

Africa, South or Central America

(especially Panama), Caribbean

islands, Mediterranean countries

(such as Turkey, Greece, and

Italy), India, and Saudi Arabia.

How this Trait is Inherited Sickle cell anemia is an inherited, lifelong

disease. People who have the disease areborn with it. They inherit two copies of thesickle cell gene—one from each parent.

If you inherit only one copy of the sicklecell gene (from one parent), you will nothave sickle cell anemia. Instead, you willhave sickle cell trait.

People who have sickle cell trait usuallyhave no symptoms and lead normal lives.However, they can pass the sickle cellgene to their children.

Signs and Symptoms• The most common symptom of

anemia is fatigue (feeling tired or

weak). Other signs and symptoms of

anemia include:

• Shortness of breath

• Dizziness

• Headache

• Coldness in the hands and feet

• Pale skin

• Chest pain

Signs and Symptoms Related to Pain

Sudden pain throughout the body is a common

symptom of sickle cell anemia. This pain is called

a "sickle cell crisis." Sickle cell crises often affect

the bones, lungs, abdomen, and joints.

A sickle cell crisis occurs when sickled red blood

cells form clumps in the bloodstream. (Other cells

also may play a role in this clumping process.)

These clumps of cells block blood flow through

the small blood vessels in the limbs and organs.

This can cause pain and organ damage.

Complications

Hand-Foot Syndrome

Splenic Crisis

- The spleen is an organ in the abdomen. Normally, it

filters out abnormal red blood cells and helps fight

infection. In some cases, the spleen may trap cells

that should be in the bloodstream. This causes the

spleen to grow large and leads to anemia.

Acute Chest Syndrome

- a life-threatening condition linked to sickle cell

anemia. It’s similar to pneumonia. The condition is

caused by an infection or sickle cells trapped in the

lungs.

Complications Priapism

- Males who have sickle cell anemia may

have painful and unwanted erections. It

happens because the sickle cells block blood

flow out of an erect penis. Over time,

priapism can damage the penis and lead to

impotence.

Multiple Organ Failure

- Multiple organ failure is rare, but serious. It

happens if you have a sickle cell crisis that

causes two out of three major organs (lungs,

liver, or kidney) to fail.

PRIAPU

S

How Is Sickle Cell Anemia Treated?

Bone Marrow Transplant

Gene Therapy

• Researchers are studying several new medicines for sickle cell

anemia. These include:

• Butyric acid. This is a food additive that may increase normal

hemoglobin in the blood.

• Nitric oxide. This medicine may make sickle cells less sticky and

keep blood vessels open. People who have sickle cell anemia have

low levels of nitric oxide in their blood.

• Decitadine. This medicine increases hemoglobin F levels (this type

of hemoglobin carries more oxygen). It may be a good choice

instead of hydroxyurea.

Prevention

You can’t prevent sickle cell anemia, because

it’s an inherited disease.

If a person is born with it, steps should be

taken to reduce complications.

Genetic Counseling should be considered.

A counselor can explain the risk of having a

child who has the disease and can help explain

the choices that are available.

Glucose 6-phosphate

dehydrogenase

deficiencyG6PD

INTRODUCTION

G6PD deficiency is the most common disease producing enzyme abnormalities in humans, affecting more than 200 million individuals worldwide.

The highest prevalence in the Middle East, tropical Africa & Asia.

G6PD Deficiency is caused by 400 different mutations in gene coding for G6PD, only few of them causes the clinical symptoms of the disease.

G6PD DEFICIENCY

G6PD is an metabolic enzyme is

involved in pentose phosphate pathway,

especially important in red blood cell

metabolism

It also protects red blood cells from the

effects of potentially harmful molecules

called REACTIVE OXYGEN SPECIES

G6PD Deficiency Mode of inheritance•

• It is X- linked recessive genetic disorder (gene is carried on X-chromosome).

• The gene is present on the X chromosome

• The inheritance follows specific pattern:

Males have one X chromosome

So, they will be diseased if they have the affected gene (xY)

Females have 2 X chromosomes

may be homozygous or heterozygous

Homozygous: are diseased (xx)

Heterozygous: are not diseased BUT: carriers (Xx)

& can transfer the disease to their sons

Male to Female ratio

Male cases are overrepresented compared with female cases.

Males are hemizygous for the G6PD gene; therefore the expression is either

normal or deficient.

In contrast, in females who have two copies of the gene on each

chromosome, the gene expression can be normal or heterozygous.

Homozygous inheritance in females can occur; whereas, heterozygous

females have genetic mosaicism secondary to X-chromosome inactivation

and can have similar manifestation as male neonates.

Who Is At Risk for Sickle Cell Anemia?

Most common in African-American males.

Many African-American females are carriers of G6PDdeficiency, meaning they can pass the gene for thedeficiency to their children but do not have symptoms;only a few are actually affected by G6PD deficiency.

People of Mediterranean heritage, including Italians, Greeks, Arabs, and Sephardic Jews, also are commonly affected.

The severity of G6PD deficiency varies among these groups — it tends to be milder in African-Americans and more severe in people of Mediterranean descent.

X-LINKED RECESSIVE HEREDITARY

A mode of inheritance in which a mutation in a gene on

the X chromosome causes the phenotype to be expressed

in males who are hemizygous.

Male = XY ( Hemizygous)

Female = XX (Homozygous)

What is favism?

G6PDH is closely linked to favism.

Favism is formally defined as hemolytic response

to the consumption of broad beans

Favism is disorder characterized by hemolytic

reaction to the consumption of broad beans

All individual with favism show G6PD deficiency

However not all individuals with G6PD

deficiency show favism

PATIENTS OF G6PD

DEFICIENCY Most indivudual with G6PD deficiency are

asymtomatic

ASYMPTOMATIC- A disease is considered to beasymptomatic if a patient is a carrier for a disease orinfection but experiences no symptoms.

Asymptomatic infections are also called subclinicalinfections.(CLINICALLY SILENT)

SYMPTOMATIC patients are almost exclusivelymale, due to the X-linked pattern of inheritence.

But female carriers can be clinically affected due tounfavourable lyonization, where randominactivation of an X-CHROMOSOMES.

Symptoms of G6PD Deficiency

paleness (in darker-skinned children paleness issometimes best seen in the mouth, especially onthe lips or tongue)

extreme tiredness

rapid heartbeat

rapid breathing or shortness of breath

jaundice, or yellowing of the skin and eyes,particularly in newborns

an enlarged spleen

dark, tea-colored urine

Why does G6PD deficiency occur more often in

certain groups of people?

It is known that Africa and the Mediterranean basin are high-risk

areas for the infectious disease malaria.

Researchers have found evidence that the parasite that causes this

disease does not survive well in G6PD-deficient cells.

So they believe that the deficiency may have developed as a

protection against malaria.

Generally this disease can be also caused by blood tranfusion.

Management of G6PD Deficiency

Since G6PD deficiency is a genetic disorder, there is no cure but

the main treatment is avoidance of oxidative stressors.

G6PD deficiency is prevented by avoiding fava beans, oxidant

drug, oxidant chemicals and other stressors.

In the acute phase of hemolysis, blood transfusions might be

necessary.

Food to avoid in G6PD deficiency