The early identification of some clinically significant hemoglobinopathies and the precise differentiation of hemoglobin variants are important to pro vide early comprehensive medical care to prevent some serious complica tions, assess prognosis, and offer genetic counseling. Laboratory approaches to screen for and confirm inherited hemoglobinopathies in children are presented. Methods include routine screening procedures as well as techniques available in research laboratories, with emphasis on readily available pro cedures. Since microcytic hypochromic anemia is the most common type of anemia in children under two years, attention is given to the differentiation of thalassemia trait from iron deficiency. The step-by-step work-up is also described for differentiating β-thalassemia from α-thalassemia.
Get full access to this article
View all access options for this article.
References
1.
Schwartz E, (Ed): Hemoglobinopathies in Children . Littleton, PSG Publishing Co. , 1980
2.
Bunn HF, Forget BG, Ranney HM: Human Hemoglobins. Philadelphia, W. B. Saunders Co., 1977
3.
Weatherall DJ, Clegg JB: The Thalassemia Syndromes. Second Edition. Oxford, Blackwell Scientific Publications, 1972
4.
International Hemoglobin Information Center.Hemoglobin4(2):215, 1980
5.
Motulsky AG: Frequency of sickling disorders in U.S. blacks. N Engl J Med288:31, 1973
6.
Goldstein MA , Patpongpanij N., Minnich V.: The incidence of elevated Hb A2 levels in the American Negro. Ann Intern Med60:95, 1964
7.
Friedman S., Atwater J., Gill FM, et al: α-Thalassemia in Negro infants. Pediatr Res8:955, 1974
8.
Huisman Thj, Jonxis Jhp: The Hemoglobinopathies—Techniques of Identification. Edited by MK Schwartz.New York, Marcel Dekker, Inc., 1978, pp 65-265
9.
Schmidt RM, Holland S.: Standardization in abnormal hemoglobin detection. An evaluation of hemoglobin electrophoresis kits. Clin Chem20: 591, 1974
10.
Milner PF, Gooden H.: Rapid citrate agar electrophoresis in routine screening for hemoglobinopathies using a simple hemolysate. Am J Clin Pathol64:58, 1975
11.
Asakura T., Ohnishi T., Friedman S., et al: Abnormal precipitation of oxyhemoglobin S by mechanical shaking . Proc Natl Acad Sci USA71:1594, 1974
12.
Schmidt RM, Wilson SM: Standardization in detection of abnormal hemoglobins: solubility tests for hemoglobin S. JAMA225:1225, 1973
13.
Ringelhann B., Khorsandi M.: Hemoglobin crystallization test to differentiate cells with Hb SC and CC genotype from SS cells without electrophoresis. Am J Clin Pathol57:467, 1972
14.
Schneider RG : Differentiation of electrophoretically similar hemoglobins—such as S, D, G, and P; or A2, C, E, and O by electrophoresis of the globin chains. Clin Chem20:1111, 1974
15.
Charache S. : Haemoglobins with altered oxygen affinity. Clin Haematol3:357, 1975
16.
Papayannopoulou T., Stamatoyannopoulos G.: Stains for inclusion bodies in CRC and Critical Review in Clinical Laboratory Science. Vol. 5. Edited by JW King and WF Faulkner.Cleveland, CRC Press Inc., 1974, pp 70-72
17.
Yataganas X. , Fessas P.: The pattern of hemoglobin precipitation in thalassemia and its significance. Ann NY Acad Sci165:270, 1969
18.
Schwartz E. : The silent carrier of beta-thalassemia. N Engl J Med281:1327, 1969
19.
Fessas Ph : Inclusions of hemoglobin in erythroblasts and erythrocytes ofthalassemia. Blood21:21, 1963
20.
Atwater J., Schwartz E.: Tests for Hb H and other unstable hemoglobins, In Hematology , Second Edition. Edited by WJ Williams, E Beutler, AJ Erslev, et al. New York, McGraw-Hill Book Company, 1977, pp 1591-1593
21.
Carrell RW, Kay R.: A simple method for the detection of unstable hemoglobins. Br J Haematol23:615, 1972
22.
Asakura T.: Automated method for determination of oxygen equilibrium curve of red cell suspensions under controlled buffer condition and its clinical application . Crit Care Med7:391, 1979
23.
Koerper MA, Mentzer WC, Brecher G., et al: Developmental changes in red blood cell volume: implication in screening infants and children for iron deficiency and thalassemia trait . J Pediatr89:580, 1976
24.
Mentzer WC: Differentiation of iron deficiency from thalassemia trait. Lancet1:882, 1973
25.
Dallman PR: New approaches to screening for iron deficiency. J Pediatr90:678, 1977
26.
Piomelli S.: A micromethod for free erythrocyte prophyrins: the FEP test. J Lab Clin Med81: 932, 1973
27.
Lamola AA, Joselow M., Yamane T.: Zinc proto-porphyrin (ZPP): a simple, sensitive flurometric screening test for lead poisoning. Clin Chem21: 93, 1975
28.
Koerper MA, Dallman PR: Serum iron concentration and transferrin saturation in the diagnosis of iron deficiency in children: normal developmental changes. J Pediatr91:870, 1977
29.
Serjeant BE , Mason KP, Serjeant GR: The development of haemoglobin A2 in normal Negro infants and in sickle cell disease. Br J Haematol39:259, 1978
30.
Schmidt RM, Rucknagel DL, Necheles TF: Comparison of methodologies for thalassemia screening by Hb A2 quantitation. J Lab Clin Med86:873, 1975
31.
Marengo-Rowe AJ: Rapid electrophoresis and quantitation of hemoglobins on cellulose acetate. J Clin Path18:790, 1965
32.
Schleider Cth , Mayson SM, Huisman Thj: Further modification of the microchromatographic determination of Hb A2. Hemoglobin1:503, 1977
33.
Atwater J., Ersley A.: Fetal hemoglobin-differential staining, In Hematology, Second Edition. EditedYork, McGraw-Hill Book Company, 1977 pp 1603-1604
34.
Kim HC, Weierbach RG, Friedman SH, et al: Detection of α or β0 thalassemia by studies of globin biosynthesis. Blood49:785, 1977
35.
Embury SH, Lebo RV, Dozy AM, et al: Organization of the α-globin genes in the Chinese a-thalassemia syndromes. J Clin Invest63:1307, 1979
