Hemoglobinopathies and Thalassemias

Hematology 251

What is a hemoglobinopathy?

Structural and functional defect of globin chains

What is thalassemia?

Reduced or absent globin chain synthesis

What sort of oxygen affinity does HgF have?

High affinity

Gene mutation? Gene deletion?

Mutation: Hemoglobinopathy

Deletion:Thalassemia

Alpha genes are found on which chromosome?

Chromosome 16

Beta genes are found on which chromosome?

Chromosome 11

Which genes are found on HbA?

2 alpha, 2 beta

Which genes are found on HbA2?

2 aplha, 2 delta

Which genes are found on HbF?

2 alpha, 2 gamma

What is a point mutation?

Replacement of one amino acid with another one

What point mutation occurs in HbS?

Replacement of 6th amino acid of a beta chain from glu > val

What point mutation occurs in HbC?

Replacement of 6th amino acid of a beta chain from glu > lys

What is homozygous?

All globin chains are abnormal

What is heterozygous?

Some, but not all, chains are abnormal

If there are no normal beta chains, what does that mean for HbA, HbA2, and HbF? What type of defect (hetero/homo) would that be?

No HbA, normal HbA2 and HbF. HbS present. Homozygous beta chain defect

If there is one normal beta chain and one abnomral beta chain, what does that mean for HbA, HbA2, and HbF? What type of defect (hetero/homo) is this?

Some HbA and HbS, normal HbA2 and HbF. Homozygous beta chain defect

If a beta chain has two different nucleotide substitutions, what does that mean for HbA, HbA2, and HbF? what kind of defect is this?

No HbA, presence of each abnormal hemoglobin, normal HbA2 and HbF. Compound heterozygous beta chain defect

What would happen to HbA, HbA2, and HbF if there is a heterozygous alpha chain defect?

All values would be low/effected due to alpha chain replacement

What happens during a homozygous alpha chain defect?

HbBarts aka hydrops fatalis. Not compatible with life.

What does it mean to have a “trait” and a “disease”

Trait: One chromosome is a carrier of the gene, often asymptomatic or mild symtpoms

Disease: Both chromosomes carry the gene, symptomatic

Which demographics are commonly seen having HbSS and HbAS?

HbSS - sickle cell disease seen in African demographics

HbAS - sickle cell trait seen in American demographic

Polymerized hemoglobin leads to what shaped cell?

Sickle cell

What happens during a sickle crisis? Does it resolve?

Hemoglobin is deprived of oxygen due to oxidating factors which causes cells to turn to rigid, sickle shapes. Shapes revert to (almost) normal oat cells once oxygen is replenished.