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Clinical Haematology > Chapter : 7 - Genetic Disorders of Haemoglobin - Thalassaemia > Flashcards

Chapter : 7 - Genetic Disorders of Haemoglobin - Thalassaemia Flashcards

1
Q

What are the three types of Haemoglobin?

A
  • Hb A - α2β2
  • Hb A2 - α2δ2
  • Hb F - α2γ2
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2
Q

What percentage of Hb A2 is found in normal adult haemoglobin?

A

1.5-3.5%

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3
Q

True or False? There is NO Hb F found in normal adult haemoglobin.

A

FALSE!! There is about 0.5% of Hb F in adult haemoglobin.

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4
Q

What is the primary Embryonic haemoglobin despite its relative instability ?

A

Hb Gower 1

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5
Q

On which chromosome is the β-globin cluster ( e, γ, δ and β) located on?

A

Chromosome 11q

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6
Q

On which chromosome is the ‘α-globin cluster’ ( ζ and α ) located on?

A

Chromosome 16p

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7
Q

True or False? In healthy individuals there are our α-globin genes and two β-globin genes .

A

TRUE!!

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8
Q

Fill in the blanks. “ All the globin genes have __________ (coding regions) and__________ (non-coding regions whose DNA is not represented in the finished protein).”

A

Three exons ( coding regions)
Two introns ( Non- coding regions)

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9
Q

Fill in the blanks. “ _________ regulates α-globin synthesis.”

A

HS-40

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10
Q

When does the main switch to adult haemoglobin from foetal haemoglobin occur?

A

3-6 months AFTER birth.

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11
Q

What is the major transcriptional factor gene regulator of the switch from foetal to adult haemoglobin?

A

BCL11A

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12
Q

Which Haemoglobin defect is found most commonly in persons of sub- Saharan African origin?

A

Hb C

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13
Q

True or False? Hb D is detected frequently in Western China and South Asia, and Hb E in South-East Asia.

A

TRUE!!

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14
Q

At which position is the Gamma ( γ)gene located?

A

The γ gene may have two sequences, which code for either a glutamic acid or alanine residue at position 136 .

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15
Q

What are examples of unstable haemoglobins?

A

Hb Köln & Hb Zurich - may result in ‘Heinz body’ congenital haemolytic anaemias.

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16
Q

True or False? Beta (β) -Thalassaemia is more common in the Mediterranean region, while Alpha( α) -thalassaemia is more common in South and South-East Asia.

A

TRUE!!

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17
Q

Which Thalassemia is Transfusion dependent?

A

Thalassemia Major

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18
Q

Which thalassemia is non- transfusion dependent with a moderate degree of anaemia due to a variety of genetic defect?

A

Thalassemia Intermedia

19
Q

What are the characteristics of Thalassemia minor?

A

Usually due to a carrier state for α- or β-thalassaemia and characterized by erythrocyte microcytosis and mild or no anaemia.

20
Q

What are the clinical features of Three alpha deletion?

A

*Moderately severe (haemoglobin 70–110 g/L) microcytic, hypochromic anaemia

  • Splenomegaly
21
Q

What is the name given to Three alpha chain deletion?

A

Hb H diseases ( a tetramer of self-associating β-globin chains, β4)

22
Q

Fill in the blanks. “A four alpha chain deletion results in __________.”

A

Hydrops fetalis

23
Q

How can one be diagnosed with Hb H disease ( Three alpha deletion )?

A

This can be detected in red cells of these patients by electrophoresis or in reticulocyte preparations

24
Q

What are the clinical features of one or two alpha chain deletion?

A
  • These are usually not associated with anaemia
  • The mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH) are LOW and the red cell count is OVER 5.5 × 1012/L.
25
Q

How is one or two alpha deletion normally diagnosed?

A

Haemoglobin electrophoresis is usually normal and DNA analysis is needed to be certain of the diagnosis.

26
Q

True or False? In Beta Thalassemia major , there is ineffective erythropoiesis and chronic haemolysisi.

A

TRUE!!

27
Q

What are the clinical features of Beta Thalassemia major?

A
  1. Severe Anaemia - 3-6 months after birth ( patient may present within the first year with failure to thrive, pallor , swollen abdomen)
  2. Enlargement of liver an spleen - ( occurs due to excessive red cell destruction, extramedullary haemopoiesis and later because of iron overload)
  3. Expansion of bones- caused by intense marrow hyperplasia leads to a thalassaemic facies and to thinning of the cortex of many bones, with a tendency to fractures and bossing of the skull with a ‘ HAIR ON END ‘ appearance on X-ray
  4. Transfusional iron overload.

5.Infections

  1. Liver disease - in thalassaemia major is most frequently a result of hepatitis C, but hepatitis B is also common where the virus is endemic. Liver disease can also be as a result of iron overload .
  2. Hepatocellular carcinoma
  3. Osteoporosis
28
Q

In Thalassemia major, which infections are likely to occur post- splenectomy?

A

Haemophilus and meningococcal infections

29
Q

Which causative agent associated with Thalassemia major due to iron over load being treated with deferoxamine can cause severe Gastroenteritis?

A

Yersinia enterocolitica

-

30
Q

” The skull is bossed with prominent frontal and parietal bones; the maxilla is also enlarged.” can be associated with which pathology?

A

Beta Thalassemia major

31
Q

What are the types of cells found in Beta Thalassemia major?

A
  • Normoblasts
  • Target cells
  • Basophilic stippling in the blood film
  • Howell - Jowell bodies
32
Q

What type of cells are found in Hb H disease?

A
  • Marked hypochromic, microcytic cells
  • Target cells
  • Poikilocytosis
33
Q

Deeply stained deposits (‘golf ball’ cells) are associated with which disease?

A

Hb H disease

34
Q

What is the stain used to identify Hb H disease?

A

Supravital staining with brilliant cresyl blue or methylene blue

35
Q

How is the diagnosis made for Beta Thalassemia major?

A
  • High-performance liquid chromatography (HPLC) is now usually used as the first-line method to diagnose haemoglobin disorders.

*HPLC or haemoglobin electrophoresis (Fig. 7.12b) reveals the absence or almost complete absence of Hb A, with almost all the circulating haemoglobin being Hb F.

  • HbA2 percentage is raised , normal or reduced .
  • Iron overload testing
36
Q

What is the treatment for Beta Thalassemia major?

A
  1. Regular Blood Transfusions - 2–3 units every 3–4 weeks.
  2. Iron chelation
  3. Regular folic acid
  4. Splenectomy
  5. Endocrine Therapy
  6. Immunization
  7. Allogenic Stem cell transplantation

8 . Gene Therapy

  1. Luspatercept - (synthetic IgG1 antibody–activin II receptor fusion protein).
37
Q

Fill in the blanks. “ A beta Thalassemia TRAIT can be diagnosed by_________.”

A

A raised level of Hb A2 (>3.5%).

38
Q

What are the clinical features of Beta Thalassemia Trait?

A
  1. Hypochromic, micro- cytic blood picture (MCV and MCH low)
  2. High Red Cell count (>5.5×1012/L)
  3. Mild anaemia (haemoglobin 100–120 g/L)
39
Q

What are the genetic causes of Beta Thalassemia Intermedia?

A
  1. Homozygous β-thalassaemia with production of more Hb F than usual, e.g. due to mutations of the BCL11A gene, or with milder defects in β chain synthesis.
  2. β-thalassaemia trait alone of unusual severity (‘dom- inant’ β-thalassaemia trait)
  3. β-thalassaemia trait in associ- ation with another mild globin abnormality such as Hb Lepore.
40
Q

What are the clinical features of Beta Thalassemia Intermedia?

A
  • Liver fibrosis & cirrhosis
  • Bone deformities and extramedullary erythropoiesis
  • Leg ulcers
  • Gallstones
  • Osteoporosis
  • Pulmonary hypertension
  • Venous thrombosis
41
Q

Fill in the blanks. “ _______________ is a type of Thalassemia Intermedia WITHOUT iron overload or extramed- ullary haemopoiesis.”

A

Hb H disease

42
Q

What is Haemoglobin Leopre?

A

This is an abnormal haemoglobin caused by unequal crossing- over of the β and δ genes to produce a polypeptide chain con- sisting of the δ chain at its amino end and the β chain at its carboxyl end.

43
Q
A

Clinical Haematology (26 decks)

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