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Global Journal of Medical Sciences Vol.x(x) pp.XXX XXXX March 2011Available online http://www.globalresearchjournals.com/journal/?id=GJMSCopyright 2011 Global Research Journals

REVIEW

Glucose 6 Phosphate dehydrogenase deficiency: A Review

M. Akram2, S. M. Ali Shah1, H. M. Asif1, Ghazala Shaheen1, Tahira Shamim1, Ashfaq Ahmed1,

Asmat Ullah2

, Khalil Ahmed1

1College of Conventional Medicine, Islamia University, Bahawalpur, Pakistan

2Shifa ul Mulk Memorial Hospital, Hamdard University, Karachi, Pakistan

Corresponding Author ;Muhammad Akram(makram_0451@hotmail.com)Address:Department of Basic Medical Sciences, Faculty of Eastern Medicine, Hamdard University, Karachi,

Madinat-al-Hikmah, Muhammad Bin Qasim Avenue, Karachi, Pakistan-74600Tel: 92-021-6440083 Fax: 92-021-6440079

Accepted xxxxxxGlucose 6 phosphate dehydrogenase is an enzyme that is usually used in hexose monophosphate shunt as a

result NADPH and riboses are obtained. NADPH is used in reduction of man y substances and riboses are usedfor DNA and RNA synthesis. If a glucose 6 phosphate dehydrogenase deficiency occurs then it leads to manydisorders including fragility of cell membrane of RBC. In this review article, introduction, epidemiology,predisposing factors, treatment and research study has been elaborated

Key Words: Glucose 6 phosphate dehydrogenase deficiency, NADPH2

Introduction

G6PD deficiency is a congenial disorder and has highfrequency in all over the world. The majority of affectedindividuals remains asymptomatic. Manifestations of

disease include hemolytic anemia, which may be due todrugs. This genetic disorder that usually affects males.This condition mainly affects red blood cells, which carryoxygen from the lungs to tissues throughout the body.G6PD deficiency results in the deficiency of NADPH2. Itaffects an estimated 400 million people and one of themost common genetic disorders worldwide. Whensomeone has G6PD deficiency, neonatal jaundice andchronic hemolytic anemia may appear. Both of theseconditions are directly related to the inability of specificcell types to regenerate reduced nicotinamide adeninedinucleotide phosphate (NADPH); this reaction is normallycatalyzed by the G6PD enzyme. It is x linked disease,

therefore males are affected and females are carriers.Patients do not show clinical manifestation until they areexposed to the precipitating factors(Beutler,1991).Precipitating factors may be oxidant drugs and severeinfections. Oxidant drugs include antibiotic, antimalarialand antipyretics(Scwartz, 2007). Individuals affected withceliac diseases are prone to hemolytic disorders that aresecondary to malabsorption of iron, vitamin B12 and folicacid. Vitamin k should be administered for correction ofcoagulopathy before endoscopy in patient with celiacdisease. But problem is that Vitamin k causes hemolysisin patient with glucose 6 phosphate dehydrogenasedeficiency. It is concluded that when vitamin k is

administered for correction of coagulopathy in patient withceliac disease, glucose 6 phosphate deficiency should beremembered(Hosnut,2010). Preeclampsia is consideredto be due to lipid peroxidation of the syncytitrophoblasplasma membrane. When capacity of cells decreases to

produce antioxidant agents then peroxidation osyncytitrophoblast increases. Reduced glutathione is mosimportant antioxidant and protects the syncytitrophoblasplasma membrane. Reduced glutathione is produced inhexose monophosphate shunt, in this pathway glucose 6phosphate dehydrogenase is a regulatory enzyme. It hasbeen observed that pregnant women with deficiency oglucose 6 phosphate dehydrogenase are more at risk fodevelopment of preeclampsia as compared to those withnormal glucose 6 phosphate dehydrogense(Abdulhad,2004)

Epidemiology

G6PD deficiency is commonly found in Middle EastMediterranean, Asia and throughout Africa. Cases ofsporadic gene mutation occur in all population. Glucose 6phosphate dehydrogenase deficiency is the most commonenzymopathy in man. G6PD deficiency is a geneticdisorder. It affects more than 400 million people in theworld. Patients with this disorder have protection againsmalaria caused by Plasmodium falciparum (Beutler, 2008Ruwende,1995). The geographical correlation of itsdistribution with the historical endemicity of malariasuggests that this disorder has risen in frequency through

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natural selection by malaria. A retrospective study wasand data was obtained from record of 258 pediatricpatients that were enrolled in pediatric hospital in NorthJordon Patients included in this study were suffering fromglucose 6 phosphate deficiency and were admitted inhospital due to hemolytic anemia. 244 out of 258 haddeveloped h3molytic anemia due to ingestion of fava

beans and others developed hemolytic anemia due toother causes including drugs and upper respiratoryinfections. A s a conclusion, it was observed that favabean ingestion is the major precipitating factor forhemolytic anemia in patients with glucose 6 phosphatedehydrogenase deficiency(Sayer,2009). A study wascarried out to determine the frequency of glucose 6phosphate deficiency in asymptomatic Pakistanipopulation. This was a cross sectional study. In this studytotal patients were 888. Out of 888, 804 were male and 88were female. Out of 888, forty individuals had glucose 6phosphate dehydrogenase deficiency. This finding relateswith WHO data for geographical distribution of thisdisease in Pakistan. As a conclusion it was suggested that

it should be considered in the differential diagnosis ofhemolytic anemia before drug administration(Mehmood,2010). Prevalence of the deficiency iscorrelated with the geographical distribution of malaria.

Precipitating factors

Antimalarial drugs (Quinidine, Quinine). This is evidentthat antimalarial drug caude deficiency of G6PDdeficiency, but only at higher doses.

Antipyretic (Aspirin, Nonsteroidal anti-inflammatory drugs

(NSAIDs)

Anticiotics(Nitrofurantoin, Sulfa drugs)( Frank, 2005)

Drugs that should be avoided by individuals withG6PD deficiency

Dapsone, Flutamide, Mefinide cream, Methylene blue,Nalidixic acid, Nitrofurantoin, Phenzopyridine, Primaquine,Rasburicase,Sulfacetamide,Sulfamethoxazole,Sulfanilamide.

Favism

Favism is defined as a hemolytic anemia due to ingestionof fava beans. All patients with favisn show G6PDdeficiency. Only a proportion of G6PD deficiency sufferersare prone to favism. Prevalence of favism is high inSardinia(Meloni,1992). In a Thai study, favism was found3.6% of G6PD deficient children(Laosombat,2006)

Glucose 6 Phosphate deficiency and Malaria

Glucose 6 phosphate deficiency is an essential enzymefor cell to withstand oxidant stress. Glucose 6 phosphatedeficiency affects over 400 million persons worldwide. Ihas been observed that individuals with deficiency oglucose 6 phosphate are not affected by Faclciparum

malaria. This is due to impaired growth of plasmodiumfalciparum in glucose 6 phosphate dehydrogenasedeficient erythrocytes.(Ruwende, 1998)

Treatment

The main treatment for G6PD deficiency is avoidance ofoxidative stressors. Vaccination against some commonpathogens may prevent infection induced attacksGuidelines for the prevention and treatment of infection inpatients with an absent or dysfunctional spleen were firspublished by the British Committee for Standards inHaematology in 1996. First of all treat the cause. If there

is infection then treat it. If drugs are causing red blood celdestruction then stop them. In some cases transfusion isnecessary (Luzzatto, 2006). Research is being done toidentify drugs that may inhibit oxidative induced hemolysisof G6PD deficient red blood cells. Although vitamin E andselenium have antioxidant properties, their use does nodecrease the severity of G6PD deficiency. Folic acidsupplement should be given. Bed rest and transfer to ahigh care/intensive care setting is required in case offavism.

Discussion

Glucose 6 phosphate dehydrogenase is a regulatoryenzyme of the hexose monophosphate pathway, and itsdeficiency is the common worldwide. G6PD deficiency isrelatively

common in populations exposed to malaria

G6PD deficiency is one of the most common humangenetic abnormalities(Mason et al, 2007). It is the ratelimiting enzyme in hexose monophosphate pathway. It isregulated by NADP/NADPH2 . NADPH2 is a reductant andit is a derivative of water soluble vitamin, Niacin. It helps insynthesis of fatty acids as well as cholesterol. It reduceshydrogen peroxide that is highly reactive and can causedamage to deoxyribonucleic acid. NADPH2 also helps inreduction of glutathione that is present on cell membrane

of red blood cells. Glutathione is made up of three aminoacids like glycine, glutamic acid and cysteine. Glutathionewhen oxidized it can cause damage to cell membrane andfragility of cell membrane may occur. Therefore it isnecessary to keep it in reduced form. To keep it inreduced form there is need of NADPH2 . NADPH2 are

also

required by white blood cell for phagocytosis and killing ofbacteria. Any affending drugs should be stopped. Infectionshould be treated. Blood transfusion is usuallyhelpful(Cappellini et al, 2008). Glucose 6 phosphatedehydrogenase deficiency is considered a cause ohemolytic anemia that leads to jaundice. Jaundice is dueto oxidant response. A case of kernicterus was reported in

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Panama. This is reported in a newborn with glucose 6phopsphate dehydrogenase deficiency that was clothed innaphthalene impregnated garments. Manifestations in thisnewborn were reported including reduced psychomotordevelopment, absence of speech, neurosensoryhypoacousia and poor reflex of the pupil to light. As aconclusion, it was suggested that use of naphthalene in

stored clothes is a common in all over the world, thereforeit is necessary to screen the newborn for glucose 6phosphate dehydrogenase deficiency, in this way severeclinical consequences can be prevented.(Gladys,2008). Ithas been observed that blood donation from a patient withglucose 6 phosphate deficiency and sickle cell trait mayalter the quality of blood that is donated,. This alteration inquality may occur during processing, storage, or inrecipient circulatory system. A study was done in Riyadh.This was a cross sectional study that was done in kingkhalid University Hospital in Riyadh. Total patient were1150. Out of 1150, 23 were diagnosed for sickle cell trait,9 for glucose 6 phosphate dehydrogenase deficiency and4 for both conditions. As a conclusion, it was suggested

that blood donors should be screened for sickle cell traitand glucose 6 phosphate dehydrogenase deficiencies. Inthis way, complications may be prevented (Alabdulaali,2010).

Conclusion

G6PD is a key regulatory enzyme of pentose phosphatepathway. It is an inherited disease characterized byhemolytic anemia. It is X linked disease. Precipitatingfactors include oxidant drugs and severe infection.Treatment includes stopping of precipitating drugs,treating infection, blood transfusion.

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