EMQ: General (Haemoglobinopathy)

A. Haemoglobin C homozygote

B. Haemoglobin Constant Spring

C. Haemoglobin D compound heterozygote

D. Haemoglobin E homozygote

E. Haemoglobin H disease

F. Haemoglobin Lepore compound heterozygote

G. Haemoglobin M disease

H. Haemoglobin S homozygote

For each of the following scenarios (1-5), choose the haemoglobin abnormality from the list above (a-h) that would BEST explain the clinical and laboratory findings based on the information given in each case. Each answer may be used once, more than once or not at all

Question 1

10 year old Ghanaian girl newly arrived with her family in the UK under investigation for mild jaundice and anaemia. Blood film shows multiple irregularly contracted cells, target cells and ‘clumping’ of haemoglobin

Question 2

8 month old child with poor feeding, lethargy, mild jaundice and hepatosplenomegaly. Haemoglobin 6.3g/dl, MCV 62fl, MCH 22pg. Blood film reveals anisopoikilocytosis, hypochromia and microcytosis but no sickling. Alkaline cellulose acetate electrophoresis shows a bands migrating to the level of HbS, HbA2 and HbF but not HbA. Acid agarose electrophoresis shows a bands migrating to the level of HbA and HbF but not HbS. Sickle solubility test is negative

Question 3

2 year old boy visiting the UK with his family from Thailand presents to the paediatric emergency department with jaundice, hepatosplenomegaly and leg ulcers. Abdominal ultrasound scan reveals numerous gallstones. Serum LDH is elevated, the direct antiglobulin test is negative. Blood film reveals microcytosis, severe anisopoikilocytosis, target cells and spherocytes but an inappropriately low reticulocyte count, and supravital staining reveals inclusions in around 5% of red cells. High performance liquid chromatography reveals a haemoglobin variant with an unusually long retention time

Question 4

4 year old boy with recurrent painful fingers presenting with severe anaemia, abdominal pain and jaundice. Haemoglobin 7.2g/dl, MCV 78fl, MCH 25pg. Blood film and haemoglobinopathy screen are awaited

Question 5

6 month old infant with failure to thrive and recurrent cyanotic episodes but no cardiac or respiratory symptoms and normal oxygen saturation on pulse oximetry

Answers:

1: Haemoglobin C homozygote

2: Haemoglobin Lepore compound heterozygote

3: Haemoglobin Constant Spring

4: Haemoglobin S homozygote

5: Haemoglobin M disease

Explanation:

Sickle cells may be present in HbSC disease, but not in HbCC which would give a mild haemolytic anaemia and characteristic target cells, crystallised haemoglobin 'rods', microspherocytes and some irregularly contracted cells on the blood film. β thalassemia major may present with severe anaemia and jaundice in infancy, if not detected antenatally, and can be caused by the δ/β fusion Hb Lepore coninherited with another β thalassemia mutation. α thalasemia phenotype and an abnormal HPLC peak with long retention time suggests the presence of Hb Constant Spring, whose RNA is unstable, and whose presence exerts a 'dominant negative' effect by suppressing expression of any normal α globin gene expression.The final case is a typical dactylitis presentation of sickle cell disease, for which homozygous HbS is the only option in this list that could be responsible, although any sickling compound heterozygous condition may present like this.

References:

Ryan, K., Bain, B. J., Worthington, D., et al (2010), Significant haemoglobinopathies: guidelines for screening and diagnosis. British Journal of Haematology, 149: 35–49.