The high rate of consanguineous marriage in Tunisia suggests a high incidence of autosomal recessive disorders. Thus is the first Tunisian published study, presenting the confirmation of the GSD1-type b. In fact, the definitive diagnosis is based on measuring the enzymatic activity of G6PT1 on a non-frozen liver biopsy. This technique is not available in Tunisia.

The clinical manifestations of glycogen storage disease type 1b are heterogeneous, most are healthy at birth and clinical symptoms appear gradually in varying degrees. The deficiency of the glucose 6-translocase T1 system generally appears around 4 to 6 months (sometimes earlier).

In the present study, the first clinical signs appear at an average age of 4 months with a time interval ranging from 2 months to 8 months, which is consistent with the data in the literature [9].

In this study, the metabolic phenotype of GSD 1b patients was characterized by episodes of hypoglycemia. This main biological parameter of the disease causes seizures associated with lactic acidosis which clinically often results in hyperventilation; the latter is a parameter that parents can easily watch over [12].

In addition, the three patients (MB, MT and SI) have presented episodes of hypoglycemia ranging from 0.55mmol/l to 2.09mmol/l; besides, the reason for consultation of SI was respiratory distress, which is consistent with data from the literature [13].

The accumulation of glycogen in the liver is due to the impossibility of transforming it into glucose, this accumulation causes hepatomegaly which is manifested by abdominal distension. It is noteworthy to mention that this symptom represented the main reason for consultation in the most studied patients (for 83% of cases) with glycogen storage disease type 1b [14].

In this serie, all patients presented with hepatomegaly at diagnosis, but only the 2nd patient consulted mainly for abdominal distension. These data are in agreement with the literature [14]. In addition, an Egyptian study showed that 90% of patients with GSD 1b also had chubby facies [15]. In this study, only the first patient MB of the first family developed large, well-filled cheeks.

Neutropenia turned out to be specific to type 1b glycogen storage disease, which leads to cause recurrent infections and inflammatory bowel disease. Its mechanism is unknown and its absence does not exclude the diagnosis of glycogen storage disease type 1b [16].

In the present study, the studied patients developed differently the neutropenia; in fact, patient MB had mild neutropenia of 1550/mm3, while the two patients MT and SI presented moderate neutropenia of 500 and 590mm3 respectively. Furthermore, patient SI suffers with recurrent E. coli pyelonephritis-like infections.

Dietary management is essential in the treatment of patients with GSD 1b, in order to prevent hypoglycaemia and ensure satisfactory height and weight growth. In addition corn starch (maïzena®) therapy can be started at six months of age in children under 2 years at intervals of 3 to 3.5 h with a maximum interval of 4 to 5 h, once the pancreatic amylase activity was measured [17].

In the current study, molecular analysis showed two previously identified mutations in three unrelated families: the p.R300H missense mutation and the p.W393X nonsense mutation. All the the patients carried a homozygous SLC37A4 mutation due to the high parental consanguinity rate.

The instability and G6P transport activity of G6PT1 are due to the presence of different mutations in SLC37A4 gene and its helical/non helical distribution, its transmembrane helices location and its cytoplasmic N- and C- terminal domains location.