Question

You have a patient who is wanting information about the likelihood of conceiving a child with sickle cell anemia.

The mothers grandmother had the disorder.

The fathers brother has the disorder.

• Apply the concepts of epigenetics and testing to help the patient understand the disease.
• Review basic pathophysiology of the chosen disease
• Diagram in a Punnett square the likelihood that the child would have the disease.
• Describe the conversation you would have with the patient based on the outcome of the Punnett square.
  • What would you say?
  • What resources or information would you include?

Answer 1

QUESTION:

You have a patient who is wanting information about the likelihood of conceiving a child with sickle cell anemia.

The mothers grandmother had the disorder.

The fathers brother has the disorder.

• Apply the concepts of epigenetics and testing to help the patient understand the disease.
• Review basic pathophysiology of the chosen disease
• Diagram in a Punnett square the likelihood that the child would have the disease.
• Describe the conversation you would have with the patient based on the outcome of the Punnett square.
  • What would you say?
  • What resources or information would you include?

ANSWER

INRODUCTION

Sickle cell anemia is a genetic disorder where the body produces an abnormal hemoglobin called hemoglobin s. Hemoglobin is the protein in red blood cells that carries oxygen. Red blood cells are normally flexible and round, but when the hemoglobin is defective, blood cells take on a “sickle” or crescent shape. This causes the red blood cells to get stuck inside blood vessels and block blood flow and oxygen transport to some parts of the body, thereby causing sickle cell anemia

MECHANISM/PATHOPHYSIOLOGY

When sickle hemoglobin (HbS) gives up its oxygen to the tissues, HbS sticks together .

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Forms long rods form inside RBC

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RBC become rigid, inflexible, and sickle-shaped

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Unable to squeeze through small blood vessels, instead blocks small blood vessels

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Less oxygen to tissues of body

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RBCs containing HbS have a shorter lifespan,Normally 20 days

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Chronic state of anemia

CLINICAL FEATURES:

Symptoms They vary from person to person and change over time, include:

Anemia. Sickle cells break apart easily and die, leaving you without enough red blood cells. Red blood cells usually live for about 120 days before they need to be replaced. But sickle cells usually die in 10 to 20 days, leaving a shortage of red blood cells (anemia). Without enough red blood cells, your body can't get the oxygen it needs to feel energized, causing fatigue.

Episodes of pain. Periodic episodes of pain, called crises, are a major symptom of sickle cell anemia.

Pain develops when sickle-shaped red blood cells block blood flow through tiny blood vessels to your chest, abdomen and joints. Pain can also occur in your bones.

The pain varies in intensity and can last for a few hours to a few weeks. Some people have only a few pain episodes. Others have a dozen or more crises a year. If a crisis is severe enough, you might need to be hospitalized. Some adolescents and adults with sickle cell anemia also have chronic pain, which can result from bone and joint damage, ulcers and other causes.

Painful swelling of hands and feet. The swelling is caused by sickle-shaped red blood cells blocking blood flow to the hands and feet.

Frequent infections. Sickle cells can damage an organ that fights infection (spleen), leaving you more vulnerable to infections. Doctors commonly give infants and children with sickle cell anemia vaccinations and antibiotics to prevent potentially life-threatening infections, such as pneumonia.

Delayed growth. Red blood cells provide your body with the oxygen and nutrients you need for growth. A shortage of healthy red blood cells can slow growth in infants and children and delay puberty in teenagers.

Vision problems. Tiny blood vessels that supply your eyes may become plugged with sickle cells. This can damage the retina — the portion of the eye that processes visual images, leading to vision problems.

DIAGNOSIS

• A blood test can check for hemoglobin S — the defective form of hemoglobin that underlies sickle cell anemia. In the United States, this blood test is part of routine newborn screening done at the hospital. But older children and adults can be tested, too.
• In adults, a blood sample is drawn from a vein in the arm. In young children and babies, the blood sample is usually collected from a finger or heel.
• If the screening test is negative, there is no sickle cell gene present. If the screening test is positive, further tests will be done to determine whether one or two sickle cell genes are present.
• Check for a low red blood cell count (anemia) will be done.

GENETIC COUNSELING

Two tests can be used to help expectant parents find out if their child is affected.

1. Amniocentesis, done usually at 14-16 weeks of pregnancy, tests a sample of the amniotic fluid in the womb for genetic defects (the fluid and the fetus have the same DNA). Under local anesthesia, a thin needle is inserted through the woman's abdomen and into the womb. About 20 milliliters of fluid (roughly 4 teaspoons) is withdrawn and sent to a lab for evaluation. Test results often take 1-2 weeks.

2. Chorionic villus sampling, or CVS, involves the removal and testing of a very small sample of the placenta during early pregnancy. The sample, which contains the same DNA as the fetus, is removed by catheter or a fine needle inserted through the cervix or by a fine needle inserted through the abdomen. The tissue is tested for genetic changes identified in an affected family member. Results are usually available within 2 weeks.

INHERITANCE OF SICKLE CELL ANEMIA

Sickle cell anemia is an autosomal recessive disease, meaning that it only occurs if both the maternal and paternal copies of the hbb gene are defective.

In other words, if an individual receives just one copy of the defective hbb gene, either from their mother or their father, they do not have sickle cell anemia but have what is called “sickle cell trait”. People with sickle cell trait usually do not have any symptoms or problems but they can pass the mutated gene onto their children.

There are three inheritance scenarios that can lead to a child having sickle cell anemia:

Both parents have sickle cell trait

If both parents have sickle cell trait, then there is a 25 percent risk of the child having sickle cell anemia and a 50 percent risk of them having sickle cell trait. There is also a 25 percent chance that the child will not inherit either copy of the mutated gene.

One parent has sickle cell anemia and the other has sickle cell trait

If one parent has sickle cell anemia and the other has sickle cell trait, there is a 50 percent risk that their children will have sickle cell anemia and 50 percent risk they will have sickle cell trait.

Both parents have sickle cell anemia

If both parents have sickle cell anemia, then their children will also definitely have the disease.

SOLUTION TO PRESENT PROBLEM BASED ON PUNETTE SQUARE

BASICS OF GENOTYPE:

For example, genotype for normal Hb genotype is :AA and Sickle cell anemia:aa

Dominant allele: A

Reccessive allele:a

homozygous dominant: AA

heterozygous : Aa

homozygous recessive: aa

Sickle cell anemia ia a autsomal recessive disorder.

Genotype of sickle cell anemia patient :“aa”

genotype of sickle cell anemia carrier “aA”or “Aa”

Genotype of person with normal Hb :"aa”

As mother dont have sickle cell anemia and mothers grandmother had the disorder,mother's genotype can be:Aa / AA

As Father dont have sickle cell anemia and father's brother has the disorder,father's genotype can be:Aa / AA

Chance 1:

If father and mother are normal, not carriers

Alleles	A                      A
A A	AA	AA
AA	AA

inference:100% normal children

Chance 2:

IF father is a carrier and mother is normal:

                                                       

Alleles	A              a
A A	AA	Aa
AA	Aa

Inference:50% normal children and 50%sickle cell anemia carrier children.

Chance 3:

If father is a normal and mother is carrier:    

Alleles	A                    A
A a	AA	AA
aA	aA

  

inference:50% normal children and 50%sickle cell anemia carrier children.            

Chance 4:

If father and mother are carriers:

Alleles	A                      a
A                a	AA	Aa
aA	aa

inference:25% sickle cell anemia ,50% sickle cell anemia carrier and 25% normal

CONCLUSION:

If mother and father are carriers,then only children can be sickle cell anemia patient.Other wise they can be carreir or normal.Explain all possibilities of occurance of disease and disease process.Decision should be made by parents.