Case study (44) - Sickle beta-thalassemia
Questions:
Q1. Comment on the abnormalities in the blood films.
The patient’s blood count shows:
Hemoglobin (Hb) 91 g/L
Mean corpuscular volume (MCV) 62 f/L
White blood cells (WBC) and platelets Normal
Q2. Hemoglobin electrophoresis (Figure below) has been performed on
• The patient (lane f)
• His mother (lane e)
• His father (lane d)
Appropriate controls as follows:
• Lane a: Beta-thalassemia trait
• Lane b: Sickle cell trait
• Lane c: Normal
Quantification of separated hemoglobin bands in the patient shows:
• Hb F 9%
• Hb S 86%
• Hb A2 5%
Quantification of separated hemoglobin bands in his mother shows:
• Hb F 3% (NR <1%)
• Hb A 92%
• Hb A2 5% (NR 1.5%–3.5%)
Quantification of separated hemoglobin bands in his father shows:
• Hb A 47%
• Hb S 49%
• Hb A2 3%
What is the diagnosis in the patient? What is the diagnosis of his mother and his father?
Q3. The patient has decided to marry someone who is a sickle cell trait carrier. What advice would you give?
Answers:
A1. The blood film shows hypochromic, microcytic cells with target cells, and occasional sickle cells.
The appearance of these is consistent with sickle beta thalassemia.
A2. The patient has sickle beta-thalassemia.
The patient’s mother has the beta-thalassemia trait.
His father has sickle cell trait.
In citrate agar electrophoresis, Hb C migrates to the same position as HbA2.
Agar gel electrophoresis allows the separation of Hb C and Hb A2.
The figure below illustrates the expected pattern of migration of normal and abnormal hemoglobins by citrate agar electrophoresis in a diagrammatic form.
Hb A is composed of two alpha chains and two beta chains (α2β2); Hb A2 is composed of two alpha chains and two delta chains (α2δ2); Hb F is two alpha chains and two gamma chains (α2γ2).
Patients with beta-thalassemia have impaired production of beta chains and compensate by increasing their production of Hb A2 and Hb F.
A3. The patient has sickle beta-thalassemia, and the partner is denoted sickle trait (A/S). The possible combinations for their offspring are therefore
• S/A
• S/S
• A/beta thal
• beta thal/S
There is thus a 50% chance of a significant hemoglobinopathy (S/S or S/ beta thal).
These two conditions have a similar clinical presentation and course.
Non-directional, informed counseling should be offered to the couple.
Antenatal diagnosis may be offered, with the prospect of genetic diagnosis by DNA analysis of placental tissue at 8–12 weeks of pregnancy.
High-performance liquid chromatography (HPLC) appearances for normal AS and S/beta thal are illustrated below.
|
Peak name |
Calibrated area % |
Area % |
Retention Time (min) |
Peak area |
|
Unknown |
--- |
0.1 |
1.02 |
1486 |
|
F |
0.4 |
--- |
1.09 |
4401 |
|
Unknown |
--- |
1.4 |
1.23 |
17859 |
|
P2 |
--- |
4.6 |
1.31 |
60173 |
|
P3 |
--- |
4.1 |
1.70 |
53848 |
|
A0 |
--- |
86.4 |
2.48 |
1121967 |
|
A2 |
3.0 |
--- |
3.62 |
39439 |
F concentration = 0.4% Total area: 1,299,173
A2 concentration = 3.0%
Analysis comments:
|
Peak name |
Calibrated area % |
Area % |
Retention Time (min) |
Peak area |
|
F |
0.2 |
--- |
1.09 |
4379 |
|
Unknown |
--- |
0.7 |
1.23 |
13599 |
|
P2 |
--- |
2.7 |
1.31 |
48797 |
|
P3 |
--- |
2.2 |
1.68 |
40361 |
|
A0 |
--- |
52.3 |
2.49 |
960055 |
|
A2 |
2.5 |
--- |
3.63 |
46364 |
|
S-
window |
--- |
39.3 |
4.45 |
720569 |
F concentration = 0.2% Total area: 1,834,125
A2 concentration = 2.5%
Analysis comments:
|
Peak name |
Calibrated area % |
Area % |
Retention Time (min) |
Peak area |
|
F |
21.4* |
--- |
1.15 |
350684 |
|
Unknown |
--- |
0.7 |
2.10 |
13160 |
|
A0 |
--- |
1.8 |
2.26 |
34292 |
|
A2 |
5.5* |
--- |
3.65 |
98186 |
|
S-
window |
--- |
74.2 |
4.50 |
1429406 |
F concentration = 21.4*% Total area: 1,925,729
A2 concentration = 5.5*%
* Values outside of expected ranges
Analysis comments:
 - Sickle beta-thalassemia Questions: Q1. Comment on the abnormalities in the blood films. The patient’s blood count show…){kind=link}
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