MUTATION Codon 60 (T->A); GTG(Val)->GAG(Glu)
 
AMINO ACID REPLACEMENT See above (Hb Cagliari)
TYPE OF BETA-THAL beta+ (abnormal betaX identified by IEF after labeling)
MECHANISM Thalassemic features because of severely unstable Hb which is rapidly destroyed by proteolysis
IDENTIFICATION Amplification of the beta-globin gene; sequencing
HEMATOLOGY IN HETEROZYGOTE(S) Found in a patient with thalassemia intermedia with normal parents: Hb 6.0 g/dl; splenectomy; thalassemia-like bone changes; improved after splenectomy. For hematological data see below. After splenectomy large, solitary, inclusion bodies in a limited number of RBCs

Age at:Presentation
13 months		20-28 monthsFirst Transfusion
30 months		Post-splenectomy
7 years
Hb (g/dl) 10.4 8.4 6.2 12.0
MCV (fl) 76.0 73.0 73.0 96.0
MCH (pg) 24.3 22.6 21.4 35.3
Hb A2 (%) 2.60 2.60 2.60 4.60
Hb F (%) 22.1 16.3 13.7 8.8
Reticulocytes (%) 15.8 15.0 32.0 50.6

HEMATOLOGY IN HOMOZYGOTE(S) None
OCCURRENCE In a Sardinian patient
HAPLOTYPE Not done
FOUND IN COMBINATION WITH ABNORMAL HB(S) None
FOUND IN COMBINATION WITH BETA-THAL ALLELE(S) None
OTHER INFORMATION The Hb variant is synthesized at a normal rate but is rapidly broken down (highly unstable) resulting in markedly ineffective erythropoiesis
       
REFERENCES
1. Podda, A., Galanello, R., Maccioni, L., Melis, M.A., Rosatelli, C., Perseu, L., and Cao, A.: Blood, 77: 371, 1991.

This material is from the book A Syllabus of Thalassemia Mutations (1997) by Titus H.J. Huisman, Marianne F.H. Carver, and Erol Baysal, published by The Sickle Cell Anemia Foundation in Augusta, GA, USA. Copyright © 1997 by Titus H.J. Huisman. All rights reserved. Neither this work nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, microfilming and recording, or by any information storage and retrieval systems, without permission in writing from the Author.