title: Adult onset of a Thalassemia intermedia genotype in association with a -alpha-3.7 homozygosity. Hb G-Accra [beta73(e17)Asp-->Asn] in combination with beta- and alpha-thalassemia in the same family.
abstract: We present the case of a 39-year-old male of mixed Black and Chinese Surinamese origin referred because of abdominal pain and extreme tiredness. The patient reported that he had received a single blood transfusion in his youth and presented at intake with a severe microcytic hypochromic anemia. A chest X-ray and computer tomography (CT)-scan revealed bilateral mediastinal lymphadenopathy and interstitial infiltrates. Elevated Hb F (80%) and an unbalanced synthesis ratio (beta/alpha = 0.18) were compatible with severe beta-thalassemia (thal) intermedia. DNA analysis revealed a double heterozygoty for the -88 (C-->T) and the IVS-II- 654 (C-->T) mutations in the presence of a homozygosity for the -alpha3.7 deletion. The two daughters of the proband were both heterozygous for the IVS-II-654 (C-->T) mutation and the -alpha3.7 deletion. The youngest daughter also carried the Hb G-Accra [beta73(E17)Asp-->Asn] mutation, inherited from the mother. Hb G-Accra, a mutant of presumed Ghanaian origin, described as non pathological in the carrier, is reported for the first time in combination with a severe fbeta(+)thal. The molecular background, haplotype of the mutations and a new A--> polymorphism at -309, 5' to the G(gamma) romoter, are reported.
authors.affiliation: Department of Internal Medicine, Ikazia Hospital, Rotterdam, The Netherlands.
authors.forename: Annemiek
authors.initials: A
authors.lastname: van der Padt
authors.forename: Marelle
authors.initials: M
authors.lastname: Bouva
authors.forename: Johannes J A
authors.initials: JJ
authors.lastname: Auwerda
authors.forename: Adriaan
authors.initials: A
authors.lastname: Dees
authors.forename: Cornelis L
authors.initials: CL
authors.lastname: Harteveld
authors.forename: Piero C
authors.initials: PC
authors.lastname: Giordano
mesh_terms: D000328:Adult; D017668:Age of Onset; D004252:DNA Mutational Analysis; D005192:Family Health; D005319:Fetal Hemoglobin / Q000032:analysis; D005838:Genotype; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006801:Humans; D008206:Lymphatic Diseases; D008297:Male; D017354:Point Mutation; D017085:alpha-Thalassemia / Q000175:diagnosis / Q000235:genetics*; D017086:beta-Thalassemia / Q000175:diagnosis / Q000235:genetics*
chemical_list: D006455:Hemoglobins, Abnormal; D005319:Fetal Hemoglobin; C026447:hemoglobin Korle