Pyruvate Kinase Deficiency

Question 1

A subtype of anemia which results in increased destruction of erythrocytes

Answer 1

Hemolytic Anemia

Question 2

Hemolytic anemia is coupled with an increase in RBC production because there is a decreased oxygen carrying capacity with loss of functional red blood cells which triggers

Answer 2

Erythropoetin (EPO) Production

Question 3

Refers defects in the erythrocytes themselves

Answer 3

Intrinsic hemolysis

Question 4

These are often hereditary and include the hemoglobinopathies, membrane deficiencies such as hereditary spherocytosis and elliptocytosis, enzyme deficiencies, and paroxysmal nocturnal hemoglobinuria.

Answer 4

Intrinsic hemolysis

Question 5

Refers to factors outside of the red blood cell that cause hemolysis

Answer 5

Extrinsic hemolysis

Question 6

These are almost always acquired and include causes such as infections, toxins, hypersplenism, microangiopathic hemolysis, liver disease and autoimmune hemolytic anemia

Answer 6

Extrinsic hemolysis

Question 7

The features of extravascular hemolysis are

Answer 7

Anemia, splenomegaly, and jaundice

Question 8

In hemolytic anemia, erythrocytes are most often

Answer 8

Normochromic and normocytic (MCV 80-100)

Question 9

In G6PD deficiency, the shape of RBCs is described as

Answer 9

Heinz bodies

Question 10

Helmet cells signifying destruction

Answer 10

Schisocytes

Question 11

An enzyme that catalyzes the last reaction of the glycolytic pathway

Answer 11

PYruvate Kinase

Question 12

Catalyzes the transfer of the high-­energy phosphate bond from phosphoenolpyruvate (PEP) to ADP in an irreversible step producing ATP and pyruvate

Answer 12

PYruvate kinase (PK)

Question 13

In mammals, there are four

Answer 13

PK isoforms

Question 14

Encodes PKL, expressed in the liver and some cells of the pancreas, intestine, and kidney

Answer 14

PKLR gene

Question 15

Also encodes PKR expressed in erythrocytes

Answer 15

PKLR gene

Question 16

Encodes PKM1 and PKM2 through alternative splicing

Answer 16

PKM gene

Question 17

Clinical PK deficiency with hemolytic anemia is limited to mutations of the

Answer 17

LR gene

Question 18

In affected individuals, activity of erythrocytic PK is

-Whereas PK activity in white cells, platelets, and
other tissues is normal

Answer 18

Markedly reduced

Question 19

Devoid of a nucleus, mitochondria, ribosomes, and other organelles and thus has no capacity for cell replication, protein synthesis, or oxidative phosphorylation

Answer 19

Mature eryhtrocytes

Question 20

The glycolytic production of ATP is the only source of energy production for the

Answer 20

Mature RBC

Question 21

A deficiency in the functionality of pyruvate kinase causes decreased production of

Answer 21

ATP

Question 22

Low ATP levels are responsible for erythrocyte concentration disruption, due to failure of the energy driven

Answer 22

Na+/K+ ATPase

Question 23

A consequence of this is cellular distortion, rigidity, and dehydration which leads to premature erythrocyte destruction driven mostly by the

Answer 23

Spleen and liver

Question 24

Additionally, the conversion of glucose to glucose-­6-

phosphate requires

Answer 24

ATP

Question 25

An intermediate of the hexose monophosphate pathway and the de-­novo glutathione synthesis from glycine, glutamate, and cysteine

Answer 25

G-6-P

Question 26

Made from HMP and glutathione are essential in protecting the erythrocyte against free radical production

Answer 26

NADPH

Question 27

Therefore pyruvate kinase deficiency leaves RBCs susceptible to intracellular

Answer 27

Oxidative stress

Question 28

An autosomal recessive disorder with an estimated prevalence of 1 In 300,000 live births

Answer 28

Pyruvate Kinase Deficiency

Question 29

Affects both genders equally and occurs in all races with highest incidences occuring in the Amish population and internationally in Northern Europe and Japan

Answer 29

PKD

Question 30

Which mutations are common in European patients with PK deficiency?

Answer 30

G1529 → A and the C1456 → T

Question 31

Which mutation is common in Japanese patients with PK deficiency?

Answer 31

C1151 → T

Question 32

Individuals affected by PKD are either homozygous for a single mutation

Answer 32

Compound heterozygous (2 different mutations)

Question 33

Have intermediate enzyme levels that usually do not produce clinical disease

Answer 33

PKD heterozygotes

Question 34

Can be acquired as a result of blood disorders such as leukemia, preleukemia, and refractory sideroblastic anemia

Answer 34

PKD

Question 35

Since RBCs lack mitochondria, the conversion of pyruvate to lactate regenerates

Answer 35

NAD+ from NADH

Question 36

The only method of ATP generation in RBCs

Answer 36

Glycolysis

Question 37

Physiologically, the hemoglobin of affected individuals has an increased capacity to release oxygen into the tissues due to a stalling at the level of pyruvate kinase causing

Answer 37

PEP accumulation

Question 38

PEP is converted back to 3-phosphoglycerate, leading to increased

Answer 38

2,3-BPG

Question 39

Interestingly, for a comparative hemoglobin and hematocrit level individuals with PKD have more efficient

Answer 39

Oxygen delivery

Question 40

Individuals with PKD are more resistant to

Answer 40

P. Falciparum

Question 41

The clinical severity of this disorder varies and can range from

Answer 41

Mile compensated anemia to severe anemia

Question 42

Variable clinical severity is explained, at least in part, by the existence of numerous mutant forms of the enzyme whose differing properties result in variable degrees of

Answer 42

Hemolysis

Question 43

Symptoms include jaundice, icteric sclera, and hepatosplenomegaly due to hemolysis

Answer 43

Severe PK Deficiency

Question 44

Can also result due to increased levels of bilirubin (byproduct of erythrocyte destruction) in the biliary ducts

Answer 44

Pigmented Gallstones

Question 45

Fatigue and lethargy are common in PKDs due to impaired oxygen delivery given decreased amounts of

Answer 45

RBCs

Question 46

In very severe cases of PKDs, heart failure can result from extensive anemia in newborns-­-­ this is called

Answer 46

Hydrops Fatalis

Question 47

One thing to workout when you suspect PKD is

Answer 47

LDH (Lactate Dehydrogenase)

Question 48

Decreased haptoglobin levels are a marker for

Answer 48

Intravascular Hemolysis

Question 49

Bilirubin is the byproduct of the breakdown of red blood cells. Increased bilirubin levels signify

Answer 49

Hemolysis

Question 50

Young erythrocytes that are produced by the bone marrow in times of increased red blood cell destruction

Answer 50

Reticulocytes

Question 51

High levels of reticulocytes signify

Answer 51

Hemolytic Anemia

Question 52

NADH fluorescence under ultraviolet light is a commonly used screening test for

Answer 52

PK Deficiency

Question 53

Loss of fluorescence of NADH under ultraviolet light in this test is observed as evidence of the presence of

Answer 53

PKD

Question 54

Show echinocytes (RBC with thorny projections) which have deformed shapes due to the disrupted cell membrane that occurs because of lack of energy requirements to run the Na/K ATPase pump

Answer 54

Peripheral Blood Smear

Question 55

What is the treatment for PKD?

Answer 55

Transfusions and Vitamin supplementation (folic acid and B Vitamins)

Question 56

Only indicated in severe cases due to increased risk of serious bacterial infections

Answer 56

Splenectomy