Value of Mutation Detection for Beta-thalassemia Genes in Prenatal Diagnosis of Severe Thalassemia Disease

Abstract

Abstract

Background  : Beta-thalassemia disease  is the common  severe  thalassemia   in  northeastern  part  of  Thailand  that  affects  the  quality  of life  and cost  of  treatment  in  affected  patient .   Early   prenatal  diagnosis  could  be  useful   for  couple  at risk  for  this disease  to avoid  affected  baby. Mutation  detection  for  beta-thalassemia  genes   may  be  useful in diagnosis and  prediction  of  severity  of disease  and subsequently  reduction  of   unnecessary   prenatal  diagnostic  procedure .

Objective : To  evaluate  value  of mutation  detection  for  beta-thalassemia  genes in results  and  cost – effectiveness of prenatal  diagnosis  for  severe  thalassemia  disease.

Design : Descriptive study.

Setting : Prenatal   diagnostic  clinic  ,Udonthani Hospital ,Udonthani .

Material and methods : The pregnant women attending  antenatal care clinic  between March  1997 – December 2007  with gestational  age  less than 20  weeks  were  screened  for  thalassemia  trait  by  mean corpuscular volume (MCV)  and dichlorophenol  indophenol  precipitation  test  (DCIP)  .Screening  tests  were  done in  husbands of screening positive  women and Hb typing  were  done  in  couple  with  screening  positive  both.   Couples   at risk for severe thalassemia disease in fetus  were referred to prenatal diagnostic clinic .  Mutation  detection  for  beta thalassemia  genes were  tested  in  couples  at  risk  for fetal  homozygous  beta-thalassemia  and  beta- thalassemia /hemoglobin E. 

Results : Among  2,956   pregnant women  with  positive  screening  test   and  husband  accepted screening tests , there were 259  (8.8 %)   couples  at  risk  for  severe  thalassemia disease .  56.6  %  of  risk  cases   were  beta  thalassemia/ hemoglobin E  risk and  44.4 %  were  risk  for Hb Bart’s  hydrops  fetalis  . Prenatal  diagnosis  were  performed  in  all  cases composed  of  amniocentesis  in  171  cases  and  fetal  blood sampling  in 88  cases. Mutation  detection  for  beta thalassemia  genes were tested  in  54  cases and  mutation  types were  21  cases ( 38.9 % ) of  codons  41/42 , 13  cases (24.1%) of  codon  17, 11  cases (20.4 %)  of  codon – 28 ( mild  beta⁺⁺ thalassemia )     2  cases  (3.7  %)  of  codon 71/72  , 2  cases  (3.7  %)  of  codon IVS - 1  nt 1  and  5  cases ( 9.3 %)  of  unknown  mutation genes.  Mutation  detection  for  beta- thalassemia  genes, therefore, can  reduce  unnecessary  prenatal  diagnosis  procedure  in  20.4 %  of  homozygous  beta- thalassemia  and beta-thalassemia /hemoglobin  E  . The  cost  of  mutation test   was  higher  than  saving  cost   from  unnecessary  prenatal  diagnosis  but  it  could  avoid  complications  from procedure.

Conclusion : Mutation  detection  for  beta-thalassemia  genes before  prenatal  diagnosis  could  reduced  unnecessary  procedure  in  20.4  %  of   homozygous beta-  thalassemia  and beta-thalassemia / hemoglobin E  .  This  test  should be  performed  in all  couples  at  risk  for beta-thalassemia disease  before  prenatal  diagnosis .