Glucose-6-phosphate dehydrogenase deficiency in Tunisia: molecular data and phenotype-genotype association

Abstract

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect. In this study, we aimed to perform a molecular investigation of G6PD deficiency in Tunisia and to associate clinical manifestations and the degree of deficiency with the genotype. A total of 161 Tunisian subjects of both sexes were screened by spectrophotometric assay for enzyme activity. Out of these, 54 unrelated subjects were selected for screening of the most frequent mutations in Tunisia by PCR/RFLP, followed by size-based separation of double-stranded fragments under non-denaturing conditions on a denaturing high performance liquid chromatography system. Of the 56 altered chromosomes examined, 75 % had the GdA(-) mutation, 14.28 % showed the GdB(-) mutation and no mutations were identified in 10.72 % of cases. Hemizygous males with GdA(-) mutation were mostly of class III, while those with GdB(-) mutation were mainly of class II. The principal clinical manifestation encountered was favism. Acute hemolytic crises induced by drugs or infections and neonatal jaundice were also noted. Less severe clinical features such as low back pain were present in heterozygous females and in one homozygous female. Asymptomatic individuals were in majority heterozygote females and strangely one hemizygous male. The spectrum of mutations seems to be homogeneous and similar to that of Mediterranean countries; nevertheless 10.72 % of cases remain with undetermined mutation thus suggesting a potential heterogeneity of the deficiency at the molecular level. On the other hand, we note a better association of the molecular defects with the severity of the deficiency than with clinical manifestations.

Glucose-6-Phosphate Dehydrogenase Deficiency in Children from 0 to 14 Years Hospitalized at the Pediatric Hospital David Bernardino, Luanda, Angola

“…Lower frequencies were observed in other African populations namely in the 4th Nile cataract region in Sudan [15] or in the Republic of Guinea [16]. Higher frequencies were detected among Palestinians in the Gaza Strip [8] and in Tunisia [6]. Moreover, we searched for the Mediterranean allele in the Angolan sample since there are historical references to European populations having settled in Angola, in particular the Portuguese, where this mutation is prevalent [7].…”

“…Therefore, the highest prevalence of G6PD deficiency is reported in Africa, Southern Europe, the Middle East, Southeast Asia, and the central and southern Pacific islands. However, due to migration, deficient alleles are now quite prevalent in North and South America and in some Northern European regions [5,6].…”

“…These variants reflect allelic genes located in the long arm of the X chromosome (Xq28) resulting in an X-linked recessive mode of inheritance [7,8]. More than 160 mutations have been identified as responsible for the deficiency, the majority of them consisting of single point mutations causing the replacement of amino acids [6].…”

“…Two of the most common G6PD variants are the Mediterranean G6PD B-C563T, mainly encountered in the Mediterranean areas, and the African G6PD A-202A/376G largely found in African subjects [6].…”

A multiplex method for detection of glucose‐6‐phosphate dehydrogenase (G6PD) gene mutations

“…Several methods for the detection of G6PD mutations have been reported. These include PCR-restriction length polymorphism technique [10,11], amplification refractory mutation system [12,13], denaturing high-performance liquid chromatography, single-stranded conformation polymorphism analysis [14,15], PCR high-resolution melting assay [16,17], PCR TaqMan assay [18], denaturing gradient gel electrophoresis [19], and DNA sequencing [20]. However, these methods are of low throughput and incur relatively high test costs.…”