Hemolytic Anemia in G6PD Patients - Case Study Example

Hemolytic Anemia in G6PD Patients It is mentioned in European Journal of Pediatrics that reduced amounts of glucose-6-phosphate dehydrogenase (G6PD) make erythrocytes more susceptible to hemolysis under conditions which have more oxidative stress. In the case discussed below, the ingestion of fava beans induced an oxidative stress to erythrocytes, causing acute hemolytic anemia. A Clinical Case Study: A family went to some restaurant for having a dinner where they had some dishes which had fava beans as the main constituents, the very next morning; one of their two sons was not feeling well and was continuously crying and on examination from near by medical facility, he was found to have following clinical features, Clinical Features Symptoms: Low grade fever Body aches Pallor Yellowish discoloration of skin Bluish discoloration of the lips Dark colored urine Signs: Pulse rate: 140/min Temp: 101degree Fahrenheit Jaundice Cyanosis Pallor Base Line Investigations: Severe Anemia Leukocytosis Azotemia Hyperbilirubinemia Peripheral blood smear shows blast cells Suspected diagnosis: G6PD Hemolytic Anemia associated with Fava beans ingestion. Pathophysiology of G6PD deficiency: While explaining G6PD deficiency by Family Practice Notebook, it is explained that It involves the following mechanisms As G6PD converts NADP to NADPH which prevents the oxidative damage to the cells but red blood cells depend solely on this pathway to prevent oxidative damage so R.B.Cs are the most commonly and most severely damaged population of cells due to the deficiency of this enzyme. Genetic Basis: Mark A. Belsey (1973) explained that the G6PD deficiency has got a sex linked inheritance. The phenotypic expression of the disease show great degree of variability and the reason being the presence of one euchromatic and one heterochromatic chromosome which is inactive is present in the female heterozygous individual. Pattern of X linked inheritance precludes the possibility that inactive X chromosome was either derived from paternal or the maternal side so the presence of mosaicism is essential in which paternal x in inactive in some cells and maternal X is inactive in others. Mark A. Belsey (1973) Biochemistry of the G6PD: The rigorousness of enzyme deficiency often does not associate well with the clinical severity of genetic diseases. Thus, some G6PD variants linked with rigorous enzyme deficiency, such as Union and Markham, cause no hemolytic problem, while some variants related with less severe deficiency, such as Manchester, Alhambra, and Tripler, cause chronic hemolytic anemia. The kinetic characteristics of these alternative enzymes have not explained the discrepancy. However, assessment of the normal and variant enzymes under pretended physiologic conditions, with the effects of various intermediate metabolites and co-enzymes in red cells being taken into consideration, reveal that the G6PD's from hemolytic variant subjects are strongly inhibited by a physiologic concentration of NADPH because of their high Michaelis constant for NADP or low inhibition constant for NADPH, and they are more sensitive to inhibition by ATP. These variant enzymes cannot produce enough NADPH in red cells to uphold an adequate concentration of concentrated and reduced glutathione. The nonhemolytic variant enzymes are far less susceptible to the inhibition by NADPH because of their low Michaelis constant for NADP and high inhibition constant for NADPH. The physiologic action of these nonhemolytic variant enzymes is expected to be more than 30 percent of the activity of the normal G6PD, and this activity is adequate to maintain the red cells unhemolyzed. In the figure below is the pentose phosphate pathway given on which Glucose 6 Phosphate dehydrogenase acts primarily. Reactions of the Pentose Phosphate Pathway Source: http://themedicalbiochemistrypage.org/pentose-phosphate-pathway.html Laboratory Findings: The affected boy has gone under base line investigations and the results are given below Hemoglobin: 7.1g/dl (normal: 11-13 g/dl) Reticulocytes: 6.7% (normal: 0.5-1.5%) Bilirubin: 6.4mg/dl (normal: 0.3-1.1mg/dl) Impaired Renal functions: yes (8.7 mmol/liter) (normal: 1.2-7 mmol/liter) Peripheral Blood Smear showed blast cells in excess. Differential Diagnosis: Acute hemolytic anemia which may be due to G6PD deficiency Sickle cell anemia Hereditary spherocytosis But as there was a history of fava beans ingestion, a more appropriate diagnosis was Glucose 6 Phosphate Dehydrogenase Deficiency as in these cases some oxidative stress like fava beans ingestion can trigger hemolytic episode Confirming the Diagnosis: Direct demonstration of G6PD levels were done which show decreased level of the enzymes and the tests to demonstrate this deficiency were done about 3months after the episode of acute hemolysis as during the episode false negative results can lead to misdiagnosis as reticulocytes being rich in the enzyme can give false interpretation. Treatment: The boy was immediately taken to the hospital where he was given blood cell transfusion to treat the severe anemia and initially injectable steroids were given to decrease the inflammatory response and then the boy was discharged on oral steroid for five days. Counseling of Parents: Parents were told about the food items which can again trigger this condition which mainly include the following; Never use fava beans whether these are fresh, frozen or mixed with some other vegetables or in any other form like soups etc. Do not use drugs containing quinine Do not use food products based on vitamin C. Vitamin C containing fruits and vegetables should be taken in moderation. Association of G6PD and Malaria: The plasmodium utilizes NADPH from the pentose phosphate pathway for its metabolism but it is quite deficient in G6PD deficient individuals who slow down the development of the parasite in G6PD deficient patients but after some time the plasmodium starts to produce its own enzyme so adapting to the conditions of decreased enzyme. References: 1) Marijn, Schuurman., Dick van, Waardenburg., Joost Da, Costa., Hendrik, Niemarkt., & Piet, Leroy. (2008). Pediatrics. European Journal of Pediatrics, 779- 782. Retrieved May 4, 2010, from http://www.springerlink.com/content/n2277x5732j31465/ 2) Wikipedia: The Free Encyclopedia: Glucose-6-phosphate dehydrogenase deficiency. Retrieved May 4, 2010, from Wikipedia site: http://en.wikipedia.org/wiki/Glucose-6-phosphate_dehydrogenase_deficiency#Signs_and_symptoms 3) Family Practice notebook.com: G6PD Deficiency. Retrieved May 4, 2010, from http://www.fpnotebook.com/Hemeonc/Hemolysis/G6pdDfcncy.htm 4) Mark, A. Belsey. (1973). The Epidemiology of Favism. Retrieved May 4, 2010, from http://whqlibdoc.who.int/bulletin/1973/Vol48/Vol48-No1/bulletin_1973_48%281%29_1-13.pdf 5) Medical Biochemistry Page. Introduction. Retrieved May 5, 2010, from http://themedicalbiochemistrypage.org/pentose-phosphate-pathway.html 6) Case Report. Acute massive haemolysis in children with glucose-6-phosphate dehydrogenase deficiency. Retrieved May 5, 2010, from http://www.hkmj.org/article_pdfs/hkm0604p149.pdf 7) G6PDD g6pddeficiency.org. Detailed Description of Classic G6PD Deficiency Hemolysis in the Red Blood Cells. Retrieved May 5, 2010, from http://g6pddeficiency.org/index.php?cmd=researchviewarticle&id=27 8) Botanical. Broad Bean (Broad Bean Toxicity). Retrieved May 5, 2010, from http://www.botanical-online.com/alcaloidesfavaangles.htm 9) Food and G6PD Deficiency. Retrieved May 5, 2010, from http://www.vigifavisme.com/en/aliments.html 10) Human Adaptability. Glucose-6-Phosphate Dehydrogenase (G6PD) and Malaria. Retrived May 6, 2010, from http://www.as.ua.edu/ant/bindon/ant475/g6pd/g6pd.htm 11) Medical Biochemistry Page. Introduction. Retrived May 6, 2010, from http://themedicalbiochemistrypage.org/pentose-phosphate-pathway.html Read More