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 ::  Abstract
 ::  Introduction
 ::  Material and Methods
 ::  Results
 ::  Discussion
 ::  Case Report
 ::  References
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ARTICLE
Year : 1977  |  Volume : 23  |  Issue : 4  |  Page : 189-192

Study of glycolytic intermediates in hereditary elliptocytosis with thalassemia


1 Blood Group Reference Centre, Seth G. S. Medical College, Parel, Bombay-400 012., India
2 Department of Pathology, Government Medical College, Nagpur., India
3 Clinical Investigation Laboratory, Mahal, Nagpur-2., India

Correspondence Address:
Roshan S Pavri
Blood Group Reference Centre, Seth G. S. Medical College, Parel, Bombay-400 012.
India
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Source of Support: None, Conflict of Interest: None


PMID: 615267

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 :: Abstract 

Glycolytic intermediates like ATP, DPG and GSH have been studied in a family with. hereditary elliptocytosis and thalassemia. Results indicate a fall in ATP with a concomitant rise in DPG in the Patient. Findings are discussed in relation to other data.



How to cite this article:
Pavri RS, Baxi A J, Grover S, Parande R A. Study of glycolytic intermediates in hereditary elliptocytosis with thalassemia. J Postgrad Med 1977;23:189-92

How to cite this URL:
Pavri RS, Baxi A J, Grover S, Parande R A. Study of glycolytic intermediates in hereditary elliptocytosis with thalassemia. J Postgrad Med [serial online] 1977 [cited 2020 Sep 28];23:189-92. Available from: http://www.jpgmonline.com/text.asp?1977/23/4/189/42752



 :: Introduction Top


Hereditary elliptocytosis (HE) is a rare hematological disorder which some­times occurs with other genetic abnorma­lities like sickle cell anemia, Hb C, beta thalassemia and others. [1],[2],[3],[12],[13],[16] A close linkage of Rhesus antigen with HE has been shown by a few investigators. [11],[12],[13] Biochemical investigations in HE sug­gest abnormalities in glycolytic metabo­lisms. [9],[11],[13] Marked GSH instability in two families of HE with and without hemolysis was observed by us earlier. [11] We present below biochemical changes observed in glycolytic (Embden-Meyer­hof) and pentose phosphate pathways in a family of HE interacting with thalasse­mia trait.


 :: Material and Methods Top


Hematological investigations were car­ried out according to standard methods. [8] Adenosine triphosphate (ATP) was determined by double enzyme method. [7] 2,3 -diphospho-glycerate was estimated by the modified chromotropic acid method of Bartlett. [10] Glucose-6-phosphate dehy­drogenase (G-6-PD) and pyruvate kinase (PK) were assayed as described previ­ously. [4] Glutathione (GSH) and GSH stability were determined by Beutler's procedure. [5],[6] Hemoglobin electrophoresis including Hb A 2 was performed as des­cribed by Yunis. [17] Hemoglobin F was determined by the method of Singer. [15]


 :: Case Report Top


DK, a 23 year old Maharashtrian male, pre­sented the following features on initial examin­ation.

The patient (propositus) had recurrent episo­des of mild jaundice, low grade fever and pain in the left hypochondrium usually lasting for 1-2 weeks during the last three years. He had two bouts of haematemesis during the last two months. Past history did not reveal any attack of jaundice or having taken drugs, alcohol etc. There was no history of joint swelling, leg ulcer or peptic ulcer in the past. His family consisted of three brothers and mother. Father died of lymphosarcoma at the age of 56 years. Mother was not available for investigation.

On examination, the patient was found to be of an average build with mild jaundice and moderate pallor. No sternal tenderness, glands or purpura was noticeable. Hepato-splenomegaly was present, liver being 5 cm firm and non­tender and spleen 7 cm firm and palpable below the costal margin. Other systemic examination was normal.

Hematological examination : Hb. was 9.75 gm/ dl. total WBC was 10,000/µl; differential count: P-70, L-28, M-1 and E-1. Oval cells (elliptocytes) were greater than 50%; hypcchromia and macrocytosis were present; evidence of hemo­lysis and regeneration was also present; reticu­locyte count was 8%; Hb F (Singer) was 5%; Hb A, was 4.3%. No abnormal Hb was demon­strated. Osmotic fragility was decreased. Heinz bodies were not seen; isopropyl test was nega­tive; heat stability was 0.5%; serum bilirubin level was 1 mg.%; urobilinogen was present but bile was absent. Bone marrow presented hypo­plastic-normoblastic picture. Iron staining was negative but tissue iron was abundantly present. Sideroblasts count was more than 60%. No ring sideroblast was seen. Roentgenologic examina­tion was normal.

Diagnosis of HE with thalassemia trait was arrived at after the family study [Figure 1].


 :: Results Top


Hematological findings of the patient (DK) and other brothers are presented in [Table 1]. The patient and another bro­ther (MK) showed both abnormal traits i.e. elliptocytosis and thalassemia while the third brother (KK) showed the pre­sence of elliptocytosis. The remaining brother (MRK) was normal. The family tree showing inheritance of both the genetic traits is shown in [Figure 1]. Though the patient and one brother (MK) are both having double genetic disease, the incidence of hemolytic anemia was obtained only in the former.

Biochemical findings on ATP and DPG in the patient (DK) showed reduction and increase respectively. Levels of these two phosphorous intermediates were normal in other three brothers studied. G-6-PD level was moderately raised in all four brothers while PK activity was high (p < 0.05) in the patient only, but was diminished in other three brothers [Table 2].

Normal GSH with greater stability was demonstrable in all four brothers. Methe­moglobin level was slightly raised in the patient.


 :: Discussion Top


Aberrent glycolytic metabolism in hereditary elliptocytosis has been shown by De Gruchy et al. [9] Cross sectional view of the anaerobic (E.M.) pathway and pentose phosphate pathway in HE-tha­lassemia appears to differ from HE alone, [9] or thalassemia alone. [14] De Gruchy et al, [9] have pointed out that the levels of ATP and DPG are normal in fresh cells but fall on incubation. These results differ from our own findings wherein we found reduction in ATP level by about 65% and increase in DPG by almost the same mar­gin (65%) in the patient in fresh red cells.

The difference in results of the patient from his brother (MK) who also demon­strated both the genetic abnormalities raises the question as to what causes the loss of ATP with concomitant rise in DPG? Low level of ATP has been demonstrated in diverse types of hemolytic anemias by us previously. [14] High level of PK indi­cates that the glycolytic metabolism is accelerated in the patient but is normal in the other brother (MK). Thus, taking into account overall glycolytic changes, we feel that ATP utilization is of import­ance in hereditary elliptocytosis with thalassemia. Variable expression of the disease may be responsible for difference in susceptibility to hemolysis in the patient and his brother. Further studies will be needed to elucidate this point.

 
 :: References Top

1.Aksoy, M.: The combination of hereditary elliptocytosis with heterozygous beta-­thalassemia. Acta Haemat., 30: 215-220,1963.  Back to cited text no. 1    
2.Aksoy, M. and Erdem, S.: Combination of hereditary elliptocytosis and heterozygous beta-thalassemia: A family study. J. Med. Genet., 6: 298-301, 1968.  Back to cited text no. 2    
3.Avery, M. E.: Hereditary elliptocytosis with hemoglobin C trait. A report of two cases. Bull. Johns. Hopk. Hosp.,- 98: 184­196, 1956.  Back to cited text no. 3    
4.Bapat, J. P. and Baxi, A. J.: Quantitative levels of G-6-PD, PK and GSH in normal and G-6-PD deficient individuals. Ind. J. Med. Res., 61: 1031-1035. 1973.  Back to cited text no. 4    
5.Beutler, E.: The glutathione instability of drug sensitive red cells. A new method for the in vitro detection of drug sensitivity. J. Lab. Clin. Med.. 49: 84-95, 1957.  Back to cited text no. 5    
6.Beutler, E., Duron, 0. and Kelly. B. M.: An improved method of detection of blood glutathione. J. Lab. Clin. Med., 61: 822-888, 1963.  Back to cited text no. 6    
7.Brewer, G. J. and Powell, R. D.: The ATP content of G-6-PD deficient and normal erythrocytes, including studies of a G-6­PD deficient man with elevated erythro­cyte ATP. J. Lab. Clin. Med., 67: 726-741. 1966.  Back to cited text no. 7    
8.Dacie, J. V. and Lewis, S. M.: "Practical hematology" . J. & A. Churchill, Ltd., London, 5th Edition, 1975.  Back to cited text no. 8    
9.DeGruchy, G. C . , Loder, P. B. and Hen­nessy, I. V.: Hemolysis and glycolytic metabolism in hereditary Elliptocytosis. Brit. J. Haemat., 8: 168-179, 1962.  Back to cited text no. 9    
10.Eaton, J . W., Brewer, G. J. and Grover. R. F.: Role of red cell 2, 3-DPG in the adaptation of man to altitude. J. Lab. Clin. Med., 73: 603-609, 1969.  Back to cited text no. 10    
11.Grover, S.. Baxi, A. J., Wechalekar, M. D.. Lakhe, R. T. and Parande, C. M.: Heredi­tary Elliptocytosis with hemolytic anemia. (A study of genetic markers). J. Assoc. Phys. India. 25: 293-298, 1977.  Back to cited text no. 11    
12.Morton, N. E.: The detection and estima­tion of linkage between the genes for elliptocytosis and the Rh blood type. Amer. J. Hum. Genet., 8: 80-96. 1956.  Back to cited text no. 12    
13.Nagaratnam, N., Siripala, K. A., Attapatu, A. M. P.. Undevia, J. V. and Sukumaran. P. K.: Hereditary elliptocytosis associated with beta-thalassemia and a variant of Rh (D). Acta. Hemat., 46: 232-241, 1971.  Back to cited text no. 13    
14.Pavri, R. S.: Biochemical Studies in hema­tological disorders. M.Sc. Thesis, Univer­sity of Bombay, 1977.  Back to cited text no. 14    
15.Singer. K., Chernoff. A. I. and Singer, L.: Studies en abnormal hemoglobins. Their demonstrations in sickle cell anemia and other hematologic disorders by means of alkali denaturation. Blood, 6: 413-428, 1951.  Back to cited text no. 15    
16.Van Ros, G., Seynhaeve, V. and Fiasse, L.: B+-Thalassemia, hemoglobin S. and Hereditary elliptocytosis in a Zairian Family. Acta. Haemat., 56: 241-252, 1976.  Back to cited text no. 16    
17.Yunis, J. J.: Biochemical methods in red cell genetics. Acad. Press. New York and London, 1969.  Back to cited text no. 17    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2]



 

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