Unstable haemoglobin causing haemolytic anaemia: de novo mutation in Sweden identified by PCR

J Intern Med. 1993 Mar;233(3):299-302. doi: 10.1111/j.1365-2796.1993.tb00992.x.

Abstract

A 38-year-old Swedish woman was investigated because of mild anaemia resistant to iron therapy. Mild haemolytic disease was found by routine blood tests. Neither HPLC (HbA1c quantification) nor Hb-electrofocusing revealed any major abnormal fraction, although in vitro testing of haemoglobin instability indicated the presence of unstable haemoglobin. PCR was used to amplify coding regions of the beta globin gene. Direct nucleotide sequencing of this material revealed heterozygosity for a substitution corresponding to the haemoglobin variant alpha 2 beta 2 135(H13)Ala-->Pro. This clearly unstable variant, named Hb Altdorf, has earlier been described only in a family of Italian descent. Examination of beta globin genes from six family members of the proposita by PCR followed by specific cleavage with the restriction enzyme Ban I, revealed the mutation in her two children but not in her parents or siblings. This case demonstrates that haemoglobin variants can not be ruled out as a cause of haematological disease even if the parents lack symptoms and standard tests, such as HPLC and electrophoresis/electrofocusing, do not reveal major abnormalities.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Anemia, Hemolytic / blood
  • Anemia, Hemolytic / genetics*
  • Female
  • Globins / genetics
  • Hemoglobins, Abnormal / analysis
  • Hemoglobins, Abnormal / genetics*
  • Humans
  • Pedigree
  • Polymerase Chain Reaction

Substances

  • Hemoglobins, Abnormal
  • Globins