Hemoglobinopathies

hemoglobinopathy

A disorder from abnormal globin chains.

genetic change causing hemoglobinopathy

A missense point mutation.

globin genes involved in hemoglobinopathy

α- or β-globin genes.

inheritance pattern of hemoglobinopathy

Autosomal recessive.

trait

Heterozygous carrier; usually asymptomatic.

disease

Homozygous or compound heterozygous; symptomatic.

evolutionary benefit of some variants

Protection vs severe P. falciparum malaria (in carriers).

mutation defining HbS

β6 Glu→Val.

HbS when deoxygenated

It polymerizes.

effect of polymerization on RBCs

Dehydrates and stiffens them → sickling.

complications of HbS

Hemolysis and vaso-occlusion.

common sickling triggers

Hypoxia, acidosis, dehydration, cold, infection.

classic clinical events in SCD (HbSS)

Pain crises, acute chest, stroke, priapism, infections.

infection risk in SCD

Functional asplenia/autosplenectomy.

smear features in SCD

Sickle forms, target cells, polychromasia.

inclusion body after autosplenectomy

Howell-Jolly bodies.

genetics of sickle trait (HbAS)

One βA and one βS.

symptoms in sickle trait

Usually none; ± hematuria/hyposthenuria.

electrophoresis: normal adult

A>F≈A2, no S.

electrophoresis: sickle trait (AS)

A>S (≈60% A, 40% S).

electrophoresis: SCD (SS)

S predominates; ↑F; no A.

mutation defining HbC

β6 Glu→Lys.

effect of HbC on RBCs

Dehydrates them and forms crystals.

smear features in HbC disease (CC)

Target cells; HbC crystals ("bar of gold").

typical anemia severity in CC

Mild-moderate hemolysis.

electrophoresis in CC

C predominates; no A.

electrophoresis in HbC trait (AC)

A>C (≈60% A, 40% C).

symptoms in HbC trait

Usually asymptomatic.

genotype in HbSC disease

One βS and one βC.

relative severity of HbSC vs HbSS

Generally milder than SS but still significant.

smear features in HbSC

Many target cells; ± folded/SC crystals.

electrophoresis in HbSC disease

S and C without A; often near-equal.

key complications in HbSC

Vaso-occlusive events (e.g., retinopathy, AVN).

Sickledex (solubility) test

A rapid screen where HbS precipitates → turbidity.

limitation of Sickledex

Unable to distinguish trait from disease.

causes of false negatives with Sickledex

Low HbS or high HbF (newborns).

test identifying and semi-quantifying variants

Hemoglobin electrophoresis (capillary/gel).

modern method for precise quantification

HPLC (± mass spec); DNA if needed.

dominant Hb in SS

S (↑F; no A).

dominant Hb in SC

S≈C (no A).

dominant Hb in CC

C (no A).

dominant Hb in traits (AS/AC)

A > variant.

smear hallmark for SCD

Sickle cells + target cells.

smear hallmark for HbC disease

Target cells + HbC crystals.

smear hallmark for HbSC

Many target cells ± SC crystals.

hemolysis type across these conditions

Mainly extravascular; SCD has intravascular components in crises.

trio pointing to SCD

Normocytic anemia + sickled forms + electrophoresis with S, no A.

trio pointing to HbC disease

Mild anemia + HbC crystals + electrophoresis with C, no A.

trio pointing to HbSC disease

Mild-moderate anemia + many target cells + S and C without A.

testing to separate trait from disease

Amount of variant vs A (trait has A>variant; disease lacks A).