MED1011-PCL-Week6

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Patient Summary
Young couple planning pregnancy, concerned about Thalassaemia (niece has condition). The couple are very organised and precise in their considerations for their future child and are financially stable.

Dx = **Thalassaemia**

__Definition__
Thalassaemia is a hereditary form of anaemia, particularly prevalent in people of Mediterranean or South East Asian background, which is caused by a dysfunction in the synthesis of haemoglobin.

__Genetics/Pathophysiology__
Classified according to the deficient globin chain α thalassaemia o ↑ β and ↓α globin à β globin tetramers (HbH) o Mutations are usually deletions o Controlled by 2 genes, each on chromosome 16 § 1 abnormal allele à normal § 2 abnormal à mild effect § 3 abnormal à HbH § 4 abnormal à death B thalassaemia o ↑α and ↓β globin à α globin tetramers o >100 different mutations (affects gene on chromosome 11) § 1 abnormal à mild symptoms (carrier) § 2 abnormal à need blood transfusions · Free chains precipitate à RBC haemolysis and hypoxia · Example of allelic heterogeneity o Different mutations (of different alleles) of same gene can à same disease o Difficult to test for because don’t always know what mutation to look for · If both parents are carriers: o 25% chance major, 50% chance minor/carrier and 25% normal

__Signs/Symptoms__
· Thalaessaemia minor o Either no symptoms or mild anaemia and splenomegaly · Thalaessaemia major o Anaemia o Splenomegaly o Bone deformities (skull, hands) o Bone expansion (compensatory hyperplasia of marrow) o Septicaemia

__Investigations__
· **Carrier testing** – offered if someone in family has the condition or is a known carrier · Diagnosed by o Screening tests in the newborn – heel prick for haemoglobinopathy o Based on clinical presentation o Blood tests – FBC, Hb testing

__Management__
· Medical o **Regular blood transfusions** and folate supplements o Chelation drug (deferral) – binds to and causes excretion of iron (raised levels due to transfusions) · Surgical o **Bone marrow transplant** – cure but 5% mortality o Can only be done in young patients

__Complications__
· Iron overload due to frequent blood transfusions · Infections · Slowed growth rates · Heart problems – arrhythmias, congestive heart failure · Still births – with most severe form of a-thalassaemia

__Prognosis__
· Severe forms of thalassaemia usually results in death due to heart failure between the ages of 20 to 30 · Less severe forms of thalassaemia do not result in a shorter lifespan

__Reproductive Choices__
If child is at risk of genetic condition · Acceptance of risk · Sperm/egg donor or donor embryo · Childless lifestyle · Testing in embryo or foetal testing (CVS/amniocentesis) · Adoption · Genetic counselling – see Genetics Notes