Hemophilia – a Case Study

Hemophilia – a Case Study

What are symptoms?What are symptoms?

• excessive or spontaneous bleeding into– joints, – muscles, – brain, – or other internal organs

• oozing following an injury or surgery, (having a tooth pulled)

• clotting is slowed or nonexistent

• excessive or spontaneous bleeding into– joints, – muscles, – brain, – or other internal organs

• oozing following an injury or surgery, (having a tooth pulled)

• clotting is slowed or nonexistent

Molecular Genetics of Hemophilia

Molecular Genetics of Hemophilia

• Changes in the “F8” gene– instructions for coagulation factor VIII

(protein).

http://ghr.nlm.nih.gov/gene/F8#conditionshttp://ghr.nlm.nih.gov/gene/F8#conditions

Biochemistry of the disorder

Biochemistry of the disorder

wikipedia

Mode of inheritanceMode of inheritance

• X-linked recessive • X-linked recessive

Type of MutationType of Mutation

• most common mutation in people with severe hemophilia A is

– a rearrangement of genetic material called an inversion.

– involves a large segment of the F8 gene.

• most common mutation in people with severe hemophilia A is

– a rearrangement of genetic material called an inversion.

– involves a large segment of the F8 gene.

Inversion MutationInversion Mutation

History of the diseaseHistory of the disease

• Dr. John Otto (1803), – a Philadelphian physician, – wrote of "a hemorrhagic disposition existing

in certain families" – called the affected males "bleeders."

• recognized the disorder was – hereditary – affected mostly males – passed down by healthy females.

• Dr. John Otto (1803), – a Philadelphian physician, – wrote of "a hemorrhagic disposition existing

in certain families" – called the affected males "bleeders."

• recognized the disorder was – hereditary – affected mostly males – passed down by healthy females.

IncidenceIncidence

• About 18,000 people in the United States

• Two types: – Hemophilia A

• (classic type)• represents 80% of haemophilia cases

– Hemophilia B

• in 4,000 to 1 in 5,000 males worldwide

• About 18,000 people in the United States

• Two types: – Hemophilia A

• (classic type)• represents 80% of haemophilia cases

– Hemophilia B

• in 4,000 to 1 in 5,000 males worldwide

Treatment & MaintenanceTreatment & Maintenance

• no cure for haemophilia

• controlled with regular infusions of the deficient clotting factor

• genetically engineered factor VIII from the genes of Chinese hamster ovary cells – higher purity and safety, – extremely expensive, and – not generally available

• no cure for haemophilia

• controlled with regular infusions of the deficient clotting factor

• genetically engineered factor VIII from the genes of Chinese hamster ovary cells – higher purity and safety, – extremely expensive, and – not generally available

What should parents do?What should parents do?

• Determine severity of the disease

• Get tested

• Monitor pregnancies

• Seek genetic counseling

• Determine severity of the disease

• Get tested

• Monitor pregnancies

• Seek genetic counseling

Future possibilitiesFuture possibilities

• More widely available genetically engineered protein

• Gene therapy

• More widely available genetically engineered protein

• Gene therapy