Genetic DisorderSickle Cell

What is Sickle cell Disease

Sickle Cell disease: is a genetic disorder that affects erythrocytes (RBC) causing them to become sickle or crescent shaped.

The effects of this condition due to an abnormality of the hemoglobin molecules found in erythrocytes.

Erythrocytes

Red Blood Cells

Erythropoesis

Contains Hemoglobin

Transports oxygen

100 – 120 days

No Nucleus

Squeeze through Capillaries

Smooth and round

Hemoglobin

The oxygen-carrying pigment and predominant protein in the red blood cells.

Hemoglobin forms an unstable, reversible bond with oxygen.

Oxyhemoglobin: Oxygenated ( bright red). Deoxyhemoglobin: Reduced ( purple-blue).

Hemoglobin

• Each hemoglobin molecule is made up of four heme groups surrounding a globin group.

• Heme contains iron and gives a red color to the molecule.

• Globin consists of two linked pairs of polypeptide chains.

Types of Hemoglobin

Normal

Hb A

Hb A2

Hb F

Abnormal (350)

Hb S

Hb C

Hb E

Sickle Cell DiseaseHemoglobin SS Disease

Hemoglobin SC Disease

Beta-Zero Thalassemia

Hemoglobin SB+ (Beta) Thalassemia

Sickle Cell Anemia

History

• The error in the hemoglobin gene results from a genetic mutation that occurred many thousands of years ago in people in parts of Africa, the Mediterranean basin, the Middle East, and India.

Sickle Cell Gene Severe Malaria

The origin of Sickle Cell anemia The change in cell structure arises from a change inthe structure of hemoglobin.

A single change in an amino acid causes hemoglobinto aggregate.

Sickle Cell Mutation

Hemoglobin A

Hemoglobin S

Genetic Recessive Disorder

Sickle Cell anemia is a recessive genetic disorder resulting from a mutation on chromosome 11, which is responsible for the synthesis of B – strand of the hemoglobin molecule.

It can be passed from generation to generation but is only majorly presented if the offspring has both allele for the disorder.

Inheritance of Sickle Cell Anemia

If one parent has sickle cell trait (HbAS) and the other does not carry the sickle hemoglobin at all (HbAA) then none of the children will have sickle cell anemia. There is a one in two (50%) chance that any given child will get one copy of the HbAS gene and therefore have the sickle cell trait. It is equally likely that any given child will get two HbAA genes and be completely unaffected.

Source from http://www.sicklecellsociety.org/education/inherit.htm#anchor298279

Inheritance of Sickle Cell Anemia

If both parents have sickle cell trait (HbAS) there is a one in four (25%) chance that any given child could be born with sickle cell anemia.

There is also a one in four chance that any given child could be completely unaffected.

There is a one in two (50%) chance that any given child will get the sickle cell trait.

Source from http://www.sicklecellsociety.org/education/inherit.htm#anchor298279

Inheritance of Sickle Cell Anemia

If one parent has sickle cell trait (HbAS) and the other has sickle cell anaemia (HbSS) there is a one in two (50%) chance that any given child will get sickle cell trait and a one in two (50%) chance that any given child will get sickle cell anemia.

No children will be completely unaffected.

Inheritance of Sickle Cell Anemia

If one parent has sickle cell anaemia (HbSS) and the other is completely unaffected (HbAA) then all the children will have sickle cell trait.

None will have sickle cell anemia.

The parent who has sickle cell anemia (HbSS) can only pass the sickle hemoglobin gene to each of their children.

Source from http://www.sicklecellsociety.org/education/inherit.htm#anchor298279

Sickle Cell Trait

Sickle hemoglobin (S) + Normal hemoglobin (A) in RBC

Adequate amount of normal Hb (A) in red blood cells RBC remain flexible Carrier

Do Not have the symptoms of the sickle cell disorders, with 2 exceptions:

Pain when Less Oxygen than usual Minute kidney problems

Mechanism• When sickle hemoglobin (HbS) gives up its oxygen

to the tissues, HbS sticks together – Forms long rods form inside RBC – RBC become rigid, inflexible, and sickle-shaped– Unable to squeeze through small blood vessels, instead

blocks small blood vessels– Less oxygen to tissues of body

• RBCs containing HbS have a shorter lifespan– Normally 20 days– Chronic state of anaemia

Signs and Symptoms of

Sickle Cell Anemia

Jaundice

Pain Episodes

AnemiaInfections

Ulcers on the Legs

Eye Problems

Complications associated with Sickle Cell anemia

• Sickle cells become sticky, rigid and elongated when they are not saturated with oxygen.

• They then stick together and hinders blood flow leading to a wide spectrum of complications.

Complications of Sickle Cell

Anemia

Hand-Foot Syndrome

Splenic Crisis

Acute Chest Syndrome

Pulmonary Hypertension

StrokePriapism

Gallstones

Blindness

Organ Damage

Treatments

Effective treatments are available to help relieve the symptoms and complications of sickle cell anemia, but in most cases there’s no cure.

Pain medicine: acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), and narcotics such as meperidine, morphine, oxycodone, and etc.

Heating padsHydroxyurea, Folic AcidBlood Transfusions

Screening1. Hemoglobin Electrophoresis

Simple Blood test Routine screening in high risk groups

• During pregnancy• Before anesthesia

2. Prenatal Testing Amniocentesis

16 and 18 weeks of the pregnancy small risk of causing a miscarriage (1 in 100)

Chorionic villus sampling (CVS) 9th or 10th week of pregnancy very small amount of material from the developing placenta slightly higher chance of miscarriage

The End