Abstract

Although several research works have been published which have more or less addressed G6PD deficiency in Tunisia, none of them have treated the issue with the objective of molecular characterization through a systematic representative screening study.

Biochemical and molecular characterizations were performed on a subset of 186 subjects: 144 neonates, ascertained through a neonatal screening for G6PD deficiency, including 30 deficient neonates, and 42 relatives belonging to 17 Tunisian deficient families of the above group. Forty-one samples showed a low G6PD activity using the spectophotometric method. Samples were classified into eight phenotypic groups based on G6PD level and electrophoretic mobility. DNA analysis using PCR-RFLP found at least six mutations. The A variant was the most common (n = 35), followed by Mediterranean mutation (n = 20). At least four uncharacterized other mutations have not been determined by PCR RFLP. The variant B was the predominant non-deficient variant (99%). Most deficient subjects were asymptomatic (78%). The Med variant was found to give a more decreased G6PD level, without more severe clinical manifestations. In deficient subjects, type B mobility was significantly correlated to Med mutation. A type A mobility and NEDB was significantly correlated to A mutation. G6PD levels were significantly lower in HMZ than in HTZ, without significant difference in clinical manifestations between the two groups.

Our findings provide evidence that A mutation is the most common in Tunisia, followed by the Mediterranean mutation. These two variants account for about 89% of G6PD mutant variants in Tunisia. Moreover, biochemical characterization is the first step in identifying G6PD mutations in a population that had never been explored in this interest; however, a phenotypic heterogeneity does not directly imply a molecular heterogeneity.