This patient is married to a man from Saudi Arabia whose family members require regular blood transfusions. She is concerned about the risk of genetic disorders causing anemia in her potential children. The document discusses thalassemia, a genetic blood disorder caused by defects in hemoglobin production. It explains the genetics and inheritance of alpha and beta thalassemia. The advisor would recommend confirming the blood conditions of the parents, performing lab work and genetic testing, and providing genetic counseling to help the couple understand the risks and make informed reproductive decisions.
2. Case study
Eight years later, she tells you that she is happily married
with a Saudi person from Hofuf.
They decided to start a family. Remarkably, several family
members of her husband living in the city need regular
blood transfusions.
She wonders whether her children might have an
increased risk of genetic disorder causing anemia.
5. Thalassemia
Defects in production of the α or β chains of hemoglobin
Resulting imbalance in globin chains leads to hemolysis in
the spleen or bone marrow
Increase severity with increasing number of alleles
involved
12. Genetic Counseling
Communication process of providing information and
support to individuals and families with a diagnosis and/or
risk of occurrence of an inherited disorder.
Genetic counseling is needed:
at diagnosis and during adolescence
prior to and after any genetic testing
prior to pregnancy and/or as early in pregnancy as possible
Annual follow-ups are needed to reinforce teaching.
15. References
St. Jude Children’s Research Hospital, article
Cooley’s Anemia Foundation, article
Northern California Comprehensive Thalassemia Center,
article
Torronto notes 2012
Pathoma notes
Editor's Notes
α thalassemia = gene deletions
2 genes: trans deletions
or cis deletions worse for the offsprings with a carrier spouse
3 genes: deficiency in α chains β chains bind together to form the hemoglobin HbH damages RBS
4 genes: NO α chains NO β chains in fetus YET γ chains bind together to form hemoglobin Hb Barts damages RBC fetus does not survive
----
β thalassemia = gene mutations (point mutations/ splicing site)
β thalassemia major:
- most severe form
severe anemia a few months after birth; high HbF (a,y,) at birth is temporarily protective.
α4 aggregate and damage RBCs ineffective erythropoiesis (RBC damage in bone marrow) + extravascular hemolysis (removal of circulating RBCs by the spleen).
Severe anemia erythropoietin from kidneys Massive erythroid hyperplasia (bone marrow expansion) expansion of
hematopoiesis into the skull and facial bones ('chipmunk faciei’) + extra medullary hematopoiesis with hepatosplenomegaly,
- Chronic transfusions are often necessary; leads to risk for secondary hemochromatosis
Smear showrs microcytic, hypochromic RBCs with target cells and nucleated red blood cells.
Electrophoresis shows little or no HbA with increased HbA2 and HbF.
Microscopy: microcytic target cells
Critical components of genetic counseling include:
obtaining a three-generation genetic family history (pedigree)
assessing risk for thalassemia in family members
identifying risk factors impacting medical management
(e.g., family history of other hemoglobin traits or diseases, hereditary hemochromatosis, G6PD deficiency, inherited thrombophilia, cardiovascular disease or its risk factors, diabetes, renal disease, allergies, ethnicity, consanguinity)
incorporating psychosocial information impacting the family system and relationships (e.g., location of residence, disclosure/nondisclosure of diagnosis, reliable source of emotional/social support)
assisting patients in conveying information about genetic risk to other family members
providing informed consent, pre-, and post-counseling for all genetic testing
