Molecular Characterization of Glucose-6-phosphate Dehydrogenase Deficiency in Families from the Republic of Macedonia and Genotype-phenotype Correlation

Abstract

Introduction:Glucose-6-phospahte dehydrogenase deficiency (G6PD) is one of the most common inherited disorders affecting around 400 million people worldwide. Molecular analysis of the G6PD gene identified more than 140 distinct mutations, the majority being single base missense mutations. G6PD Mediterranean is the most common variant found in populations of the Mediterranean area.Aim:The aim of our study was to perform molecular characterization of G6PD deficiency in families from the Republic of Macedonia and correlate the findings to disease phenotype.Patients and methods:Six patients and seven other family members were selected for genetic characterization, the selection procedure involved clinical evaluation and G6PD quantitative testing. All patients were first screened for the Mediterranean mutation, and subsequently for the Seattle mutation. Mutations were detected using PCR amplification and appropriate restriction endonuclease cleavage.Results:Four hemizygote and 3 heterozygous carriers for G6PD Mediterranean were detected. All G6PD deficient patients from this group showed clinical picture of hemolysis, and in 66.6% neonatal jaundice was confirmed based on history data. To our knowledge, this is the first study concerned with molecular aspects of the G6PD deficiency in R. Macedonia.Conclusion:This study represents a step towards a more comprehensive genetic evaluation in our population and better understanding of the health issues involved.

Favism: A Case Report

“…Detecting G6PD activity during a hemolytic crisis can be problematic, and activity within the normal range cannot rule out the diagnosis because older RBCs, which have less enzymatic activity, are the first to hemolyze, while the younger RBCs, with almost normal enzymatic activity, remain in circulation. In this case, a G6PD deficiency was detected during the hemolytic crisis, supporting the diagnosis of class II, probably a Mediterranean-type G6PD deficiency [ 10 ]. In most cases, the hemolytic crisis is self-limiting once exposure to the trigger is stopped, as occurred in our case [ 3 ].…”

Referentne vrijednosti za kvantitativno ispitivanje G6PD deficita kod novorođenčadi iz Republike Sjeverne Makedonije

“…The average value of the enzyme G6PD expressed as a percentage of normal enzyme activity was calculated according to the reference range of the used diagnostic test. The reference values of the commercial diagnostic test ranged from 245 to 299 (272 ± 27) mU/10 9 erythrocytes; values that were significantly higher than those obtained in our patient population (19,20). It would therefore be more appropriate to establish population-specific reference value (range) for the appropriate diagnostic test and to compare the results with this value.…”

“…The average value of the enzyme G6PD, expressed as a percentage of the normal enzyme activity, was 0.84 ± 0.1%. The reference values of the commercial diagnostic test used in the quantitative spectrophotometric method ranged from 245 to 299 (272 ± 27) mU/10 9 Er (18,19). Compared with the activity of the enzyme registered in the population of the healthy newborns from the Republic of North Macedonia, a significant difference has been noticed.…”

“…Commercially available kits (AMS U.K. Ltd, East Sussex, U.K.) were used to perform the test (86,114). Values of 245 to 299 (272 ± 27) mU/10 9 erythrocytes were considered normal (18,19).…”

Nonsynonymous amino acid changes in the α-chain of complement component 5 influence longitudinal susceptibility to Plasmodium falciparum infections and severe malarial anemia in kenyan children

“…Bacterial comorbidity was assessed by culture and sensitivity assays following our previously published protocols ( Were et al, 2011 ). Glucose six phosphate dehydrogenase (G6PD) deficiency (levels: normal, intermediate, deficient) was determined following the methods of Cherepnalkovski et al , ( Cherepnalkovski et al, 2015 ). The α 3.7 deletion produces an HBA2/HBA1 hybrid gene and a 3.7 kb deletion ( Borg et al, 2009 ).…”