thalassaemias

thalassaemias

1. beta-thal

   • most often occur in people from
     • Indian subcontinent
     • Mediterranean
     • Middle East
   • 2 types- both have severe reductn in prodn beta-globin (& so drop in HbA prodn)
     • disease severity depends on amount of residual HbA & HbF prodn
       • beta-thal major
         • MOST SEVERE FORM
         • can't make HbA (alpha2 beta 2) cos of abnormal beta-globin gene
         • clinical features
           • pallor
           • jaundice
           • bossing of skull & maxillary overgrowth
           • hepatosplenomegaly
           • need for repeated blood transfusions
       • beta-thal intermedia
         • milder form & variable severity
         • beta-globin mutations allow small amount of HbA &/or large amount of HbF to be made
   • clinical features
     • severe anaemia
       • transfusion-dependent
       • from age 3-6 months old
       • + jaundice
     • failure to thrive/growth failure
     • extramedullary haemopoiesis
       • prevent by regular blood transfusions
         • if not prevented ->
           • hepatosplenomegaly
           • bone marrow expansion
             • -> classical facies
               • maxillary overgrowth & skull bossing
                 • rare in developed countries
   • Mx
     • lifelong monthly RBC transfusions
       • beta thal fatal w/o these
       • aim= keep [Hb] > 10g/dl
         • to reduce growth failure
         • to prevent bone deformation
       • cause chronic Fe overload (cos repeated)
         • ->cardiac failure
         • ->liver cirrhosis
         • ->diabetes
         • ->infertility
         • ->growth failure
         • so Rx w/ ... from 2-3 years old
           • iron chelation e.g. subcut desferrioxamine
           • oral iron chelator drug e.g. deferasirox
           • compliance hard but good comp w/ both -> 90% chance of living til 40s
             • if can't comply, high mortality in early adulthood from overload
       • complications of multiple transfusions
         • iron deposition
           • the most imp complication
             • seen in all pts
           • heart-cardiomyopathy
           • liver-cirrhosis
           • pancreas- diabetes
           • pituitary gland- delayed growth & sexual maturation
           • skin-hyperpigmentation
         • antibody formation (10% of kids)
           • allo-antibodies to transfused RBCs in pts make finding compatible blood hard
         • infection (now uncommon <10% of kids)
           • hepatitis A, B, C
           • HIV
           • malaria
           • prions e.g. new variant CJD
         • venous access
           • common prob
           • often traumatic in young kids
           • may need central venous access device e.g. portacath
             • predispose to infection
     • bone marrow transplantation
       • the only cure
       • only for kids w/ an HLA-identical sibling
         • cos then 90-95% chance of transfusion independence & long-term cure (success) but 5% chance of transplant-related mortality
   • prenatal diag
     • for parents both heterozyg for beta-thal
       • means 1 in 4 risk of having an affected child
     • offer DNA analysis of chorionic villus sample + genetic counselling
       • help parents make informed decision re to continue preg

2. beta-thal trait

   • heterozygotes usually asymptomatic
   • hypochromic & microcytic RBCs
     • so can be confused w/ mild iron def
       • tell apart by measuring serum ferritin
         • low in iron def NOT beta thal trait
           • measure serum ferritin in pts w/ mild anaemia & microcytosis before starting iron supplements
             • avoid unnecessary Fe therapy
   • mild or absent anaemia
     • + disprop drop in MCH (18-22 fl) & MCV (60-70 fl)
       • so RBC count usually raised (> 5.5 x 10^12/L)
   • raised HbA2= most imp diag feature
     • usually seen in about 5%
   • mild elevatn of HbF by 1-3% in 50%

3. alpha-thal

   • manifestation depends on no of functional alpha-globin genes
     • alpha-thal major
       • aka Hb Barts hydrops fetalis
       • cause= deletion of all 4 alpha globin genes
         • so no HbA (alpha2 beta2) can be made
       • occurs in families of S. East Asian origin
       • presents mid-trimester
         • fetal hydrops (oedema & ascites)
           • from fetal anaemia
           • always fatal in utero or within hours of delivery
             • long-term survivors are those who got monthly intrauterine transfusion til delivery + lifelong monthly transfusions after birth
       • diag
         • Hb electrophoresis
         • Hb HPLC (high performance liquid chromatography)
           • only shows Hb Barts
     • HbH disease
       • 3 of alpha-globin genes deleted
       • px often = mild-moderate anaemia
       • some pts transfusion-dependent
     • healthy ppl have 4 func alpha-globin genes
     • alpha-thal trait
       • = deletion of 1 or 2 alpha-globin genes
       • asymptomatic
       • mild/absent anaemia
       • hypochromic & microcytic RBCs
         • so can be confused w/ iron def