Red Cell Enzyme Defects

Question 1

What is the mode of inheritance with Pyruvate Kinase Def and chromosome affected?

Answer 1

Autosomal recessive. The gene is on chromosome 1q21

Question 2

What is the clinical presentation of pyruvate kinase def?

Answer 2

Neonatal jaundice/jaundice later in life, non-spherocytic hemolytic anemia, gall stones, cholestasis, osteoporosis, pulm HTN, iron overload, thromboembolism

Question 3

When checking for enzyme activity in Pyruvate Kinase Def when can it be normal and how do you reassess it?

Answer 3

The enzyme activity level can be normal esp in the presence of a high reticulocyte count or someone who has no spleen. Check the relative proportion of the enzyme compared to G6PD and hexokinase

Question 4

What is the medication that has been approved for Pyruvate Kinase Def?

Answer 4

Mitapivat

Question 5

What supportive care do you give patients with Pyruvate Kinase Def?

Answer 5

Intermittent vs chronic transfusions. Folic Acid.
Splenectomy is reserved for those requiring chronic blood tx or decreased quality of life.

Question 6

What is the most common spectrin defect seen in Autosomal Dominant Hereditary Spherocytosis?

Answer 6

Autosomal Dominant-ankyrin def is most common. (refer to notes for other types in AD disease).

Question 7

Genetically what are the ways Hereditary Spherocytosis can develop and how else can it develop?

Answer 7

You have autosomal dominant (75% cases are) and recessive forms of the disease. Additionally, you can see acquired forms of the disease.

Question 8

What is the test of choice when suspecting hereditary spherocytosis?

Answer 8

EMA-has higher specificity and sensitivity than osmotic fragility test.

Question 9

What is the enzyme affected in dehydrated hereditary stomatocytosis and what’s the mode of inheritance?

Answer 9

The enzyme that is affected is PIEZO1-responsible for K efflux and Na influx. It is autosomal dominant.

Question 10

With dehydrated hereditary stomatocytosis what is the clinical severity of symptoms and when do patients typically present? What is the MCV and MCHC?

Answer 10

The hemolytic anemia is mild in nature, patients typically present in adulthood with splenomegaly and gallstones. They can have iron overload. They have high MCV with high MCHC.

Question 11

What diagnostic tests suggest Dehydrated Hereditary Stomatocytosis?

Answer 11

Osmotic fragility will be reduced and ektacytometry profile shows left shift. EMA is normal.

Question 12

What is the defect seen in Hereditary Hydrocytosis?

Answer 12

There is a red cell defect due to RHAG or SLC4A1 mutation that causes increased intracellular Na and water and release of K.

Question 13

What is the tx and what tx is contraindicated for dehydrated hereditary stomatocytosis?

Answer 13

These patients are treated with supportive care. Splenectomy is contraindicated due to excessive risk of thrombosis

Question 14

What are the lab clinical features are seen in Hereditary Hydrocytosis (compared to dehydrated stomatocytosis)?

Answer 14

They have moderate to severe anemia with high MCV with low MCHC.

Question 15

What diagnostic tests suggest Hereditary hydrocytosis?

Answer 15

On Ektacytomery there is a rightward shift (as opposed to leftward shift with dehydrated stomatocytosis)

Question 16

What is the treatment of Hereditary hydrocytosis?

Answer 16

Supportive care, but can do splenectomy in these cases. It will not completely correct the hemolysis.

Question 17

With gardos channlopathy in dehydrated stomatocytosis what is unique here? What are the ektacytometry results?

Answer 17

They will have LOW not high reticulocyte count. Also they have much more severe symptoms and severe iron overload. Ektacytometry testing will be normal.

Question 18

What are the lab and clinical features of Hereditary Pyropoikilocytosis?

Answer 18

Patients will have a very LOW MCV with moderate to severe hemolytic anemia w/ jaundice and splenomegaly.

Question 19

What will the peripheral smear show in Hereditary Pyropoikilocytosis?

Answer 19

Marked poikilocytosis with occasional spherocytes/elliptocytes with fragmentation.

Question 20

What is the mode of inheritance of hereditary pyropoikilocytosis?

Answer 20

Autosomal Recessive

Question 21

What is the defect seen in Hereditary Pyropoikilocytosis?

Answer 21

Spectrin abnormality.

Question 22

How do you diagnose Hereditary Pyropoikilocytosis?

Answer 22

Thermal Instability-Diagnosis is made by heat sensitive RBCs that fragment when heated at 45 degrees Celsius

Question 23

What is the treatment of Hereditary Pyropoikilocytosis?

Answer 23

Splenectomy for very severe/symptomatic cases. It partially corrects the hemolysis. Avoid in less than 3 years of age.

Question 24

Before proceeding with a splenectomy in stomatocytosis what should first be done?

Answer 24

Genetic testing to confirm which type the patient has as dehydrated stomatocytosis patients can’t have splenectomy.

Question 25

What is the mode of inheritance of McLeod Phenotype and what is the symptom severity? What is the defect here?

Answer 25

It is X-linked. Males have mild compensated Hemolysis. Females are asymptomatic with few acanthocytes. Patients are missing the Kx (kell antigen) precursor protein needed for Rh antigen (which is absent).

Question 26

What is the mode of inheritance of Rh def (null) Syndrome, the defect seen, and what is the shape of the red cells?

Answer 26

Autosomal recessive. Due to absent expression of the Rh antigen. Increased cation transports leads to dehydrated cell-stomatocyte. Occasionally spherocytes.

Question 27

What are key features of abetalipoproteinemia?

Answer 27

Congenital absence of apolipoprotein B in plasma. Cholesterol is low. Autosomal recessive. They form acanthocytes. They have retinitis pigmentosa, ataxia, intention tremors, and steatorrhea.