Haematological disease in a child: Thalassaemia Flashcards
Define thalassaemia.
Inherited disorders of haemoglobin synthesis affecting a- and b-chain genes.
Explain the general aetiology/risk factors for thalassaemia.
Hb composed of 2a and 2b chains. Four genes code for a-chains (2 on eachchromosome 16) and 2 for bchains (1 on each chromosome 11). Clinical manifestation depends on the amount of genes affected.7
a-Thalassaemia results from major deletions, b-thalassaemia from single base changes, small deletions of insertional mutations. Lack of major deletions with b-thalassaemia = variable degrees of reduced b-chain production.
What are the different types of alpha-thalassaemia?
Silent carrier state: 1-gene deletion, slight descreased a-chain production but haematologically normal.
Mild a-thalassaemia: 2-gene deletions, small RBCs, mild anaemia, usually asymptomatic.
Haemoglobin H disease: 3-gene deletion causes severe anaemia, small abnormal RBCs and red cell fragments, splenic and bone changes. Haemoglobin-H formed from normal b-chain tetramers; has impaired O2 transport and leads to increase d cell breakdown secondary to membrane instability. Regular blood transfusions required.
Hydrops fetalis (a-thalassaemia major): 4-gene deletion, incompatible with life -> in utero death. Antenatally produced eta-chains associate to form Hb-Barts.
What are the different types of beta-thalassaemia?
Thalassaemia minor (trait): 1-gene b-thalassaemia; 1 normal gene and 1 affected gene (varied production of bglobin).
Thalassaemia intermedia: 2-gene b-thalassaemia (compound heterozygous state) dependent on residual b-globin production in the affected genes. Significant anaemia present but transfusions not required.
Thalassaemia major (Cooley anaemia): As intermedia but requires transfusions.
Summarise the epidemiology of alpha-thalassaemia.
5–10% (Mediterranean), 20–30% (West Africa), 68% (South Pacific), <1% North Europe.
Summarise the epidemiology of beta-thalassaemia.
>1% (Mediterranean/India/South East Asia/North Africa/Indonesia), uncommon in other areas. M>F
What are the presenting signs and symptoms of minor thalassaemia?
Normal examination, usually asymptomatic.
What are the presenting signs and symptoms of major thalassaemia?
Variable presentation but may include severe pallor, slight to moderately severe jaundice, marked hepatosplenomegaly, growth retardation, bony abnormalities (frontal bossing, prominent facial bones and dental malocclusion), complications of severe anaemia (exercise intolerance/cardiac murmur/CCF), signs of endocrinopathy caused by iron deposits (secondary iron overload). Diabetes and thyroid or adrenal disorders.
What are some appropriate investigations for thalassaemia?
Bloods: Low Hb, low MCV/MCH, high WBCs, left shift, normal platelets, high serum Fe2/ferritin level.
Peripheral blood film: Marked hypochromasia and microcytosis, hypochromic macrocytes (polychromatophilic cells), nucleated RBCs, basophilic stippling and occasional immature leucocytes.
Hb electrophoresis: High Hb-F/Hb-H/Hb-Barts. Imaging: Bone surveys, AUSS.
What is the medical management plan for thalassaemia?
Genetic counselling (mild/trait). Blood transfusion with chelation therapy may be required. Deferasirox (PO chelation agent) minimises Fe2+ accumulation and hence overload. Parenteral desferrioxamine (DFO) may also be used in combination with PO therapy. Haematopoietic stem cell transplantation for selected patients.
What is the surgical management for thalassaemia?
Splenectomy may be necessary via the open approach if massive splenomegaly present. Placement of a CVC/Portacath for venous access for transfusions.
What are some complications associated with thalassaemia?
Fe2+ overload, reduced growth, sexual development, reduced fertility, osteoporosis, osteopenia, diabetes mellitus, hypothyroidism, hypoparathyroidism, hypoadrenalism.
What is the prognosis of thalassaemia?
Dependent on thalassaemia severity/Fe2 overload/age at diagnosis.
