Hereditary RBC membrane defect

Question 1

What is the MCHC range in hereditary spherocytosis?

Answer 1

35-38 g/dL, higher than the normal range of 31-37 g/dL

Question 2

What inheritance pattern does hereditary spherocytosis follow?

Answer 2

Autosomal dominant (75%)

Question 3

Which proteins are deficient in hereditary spherocytosis?

Answer 3

Ankyrin, Band 3, α-Spectrin, β-Spectrin, Protein 4.2

Question 4

What causes the defect in hereditary spherocytosis?

Answer 4

Disruption of vertical membrane interactions between transmembrane proteins and the cytoskeleton, leading to loss of membrane and decreased surface area-to-volume ratio

Question 5

Hereditary spherocytosis MCHC value in patients

Answer 5

35 to 38 g/dL (high MCHC) because of spherocytosis

Question 6

Normal MCHC range

Answer 6

31 to 37 g/dL

Question 7

Inheritance pattern of hereditary spherocytosis

Answer 7

Autosomal dominant (75%)

Question 8

Deficient proteins in hereditary spherocytosis

Answer 8

Ankyrin, Band 3, α-Spectrin, β-Spectrin, Protein 4.2

Question 9

Definition of hereditary spherocytosis

Answer 9

Defect in protein(s) disturbing vertical membrane interactions, leading to loss of membrane and decreased surface area-to-volume ratio

Question 10

Elasticity of RBC membrane in hereditary spherocytosis

Answer 10

Stretchable but less elastic

Question 11

Spleen’s impact on spherocytes

Answer 11

Low pH, ATP, and glucose; decreases RBC’s ability to tolerate osmotic changes, leading to swelling and lysis

Question 12

Effect of splenectomy in hereditary spherocytosis

Answer 12

Normal RBC survival, fewer complications from chronic hemolysis

Question 13

Most sensitive and specific test for hereditary spherocytosis

Answer 13

EMA binding test (Eosin-5’-maleimide)

Question 14

Test choice for hereditary spherocytosis

Answer 14

EMA binding test (best choice), Flow cytometry (2nd choice)

Question 15

Hereditary elliptocytosis inheritance pattern

Answer 15

Autosomal Dominant

Question 16

Deficient proteins in hereditary elliptocytosis

Answer 16

α-Spectrin, β-Spectrin, Protein 4.1

Question 17

Characteristics of hereditary elliptocytosis

Answer 17

Defect in proteins disrupting horizontal linkages in the cytoskeleton, leading to loss of membrane mechanical stability

Question 18

Southeast Asian ovalocytosis inheritance pattern

Answer 18

Autosomal dominant

Question 19

Deficient protein in Southeast Asian ovalocytosis

Answer 19

Band 3

Question 20

Characteristics of Southeast Asian ovalocytosis

Answer 20

Increased membrane rigidity, resistant to malaria, prevalent in Southeast Asia

Question 21

Overhydrated hereditary stomatocytosis inheritance pattern

Answer 21

Autosomal dominant

Question 22

Deficient protein in overhydrated hereditary stomatocytosis

Answer 22

Rh-associated protein (RHAG), others unknown

Question 23

Characteristics of overhydrated hereditary stomatocytosis

Answer 23

Increased membrane permeability to sodium and potassium, increased intracellular sodium, influx of water, increased cell volume, decreased cytoplasmic viscosity, typical RBC morphology: stomatocytes (5% to 50%) and macrocytes

Question 24

Dehydrated hereditary stomatocytosis inheritance pattern

Answer 24

Autosomal dominant

Question 25

Deficient protein in dehydrated hereditary stomatocytosis

Answer 25

Piezo-type mechanosensitive ion channel component 1

Question 26

Characteristics of dehydrated hereditary stomatocytosis

Answer 26

Increased membrane permeability to potassium, decreased intracellular potassium, loss of water from cell, decreased cell volume, increased cytoplasmic viscosity, typical RBC morphology: target cells, burr cells, stomatocytes (<10%), RBCs with ‘puddled’ hemoglobin at periphery, desiccated cells with spicules

Question 27

RBC membrane composition

Answer 27

8% carbohydrates, 40% lipids, 52% proteins (integral and peripheral)

Question 28

Transmembrane protein function in RBCs

Answer 28

Channel ions, water, and glucose; anchor membrane receptors; connect lipid bilayer to cytoskeleton for membrane integrity

Question 29

Aquaporin 1 function

Answer 29

Water transporter

Question 30

Band 3 protein function

Answer 30

Anion transporter, supports ABH antigens

Question 31

Ca2+-ATPase function

Answer 31

Ca2+ transporter

Question 32

Duffy protein role

Answer 32

Supports Duffy antigen

Question 33

Glut-1 function

Answer 33

Glucose transporter, supports ABH antigens

Question 34

Glycophorin A role

Answer 34

Transports negatively charged sialic acid, supports MN determinants

Question 35

Glycophorin B function

Answer 35

Transports negatively charged sialic acid, supports Ss determinants

Question 36

Glycophorin C role

Answer 36

Transports negatively charged sialic acid, supports Gerbich system determinants

Question 37

ICAM-4 function

Answer 37

Integrin adhesion

Question 38

Kell protein role

Answer 38

Zn2+-binding endopeptidase, supports Kell antigens

Question 39

Kidd protein function

Answer 39

Urea transporter

Question 40

RhAG function

Answer 40

Necessary for expression of D and CcEe antigens; gas transporter, likely CO2

Question 41

Function of skeletal proteins in RBCs

Answer 41

Provide lateral support for the membrane; determine shape and flexibility

Question 42

α-spectrin and β-spectrin role

Answer 42

Primary cytoskeletal proteins

Question 43

Adducin function

Answer 43

Caps actin filament

Question 44

Ankyrin function

Answer 44

Anchors band 3 and protein 4.2

Question 45

Dematin function

Answer 45

Actin bundling protein

Question 46

F-actin function

Answer 46

Binds β-spectrin

Question 47

Protein 4.1 function

Answer 47

Anchors 4.1 complex

Question 48

Protein 4.2 function

Answer 48

Anchors Ankyrin complex

Question 49

Tropomodulin role

Answer 49

Caps actin filament

Question 50

Tropomyosin function

Answer 50

Regulates actin polymerization