Primary hyperoxaluria type 1 (PH1), is a rare and heterogeneous disease and one of major causes of renal insufficiency in Tunisia, caused by mutations in the AGXT gene. 33-34InsC mutation, was mainly described in children with a severe clinical feature leading to early death, but it was uncommonly reported in adult patients. Common mutations in AGXT were tested using PCR/RFLP technique in 111 patients (68 adult, 43 children) with suspected PH1. We described 16 cases (eight adult and eight children) with a 33-34InsC mutation with a median age of 24 years [6 months - 73 years]. All children were in end stage renal disease (ESRD) at the median age of 3 years due to lithiasis and/or nephrocalcinosis. Unfortunately, 75% of them died with a median age of 2.5 years. For the majority of adults only spontaneous elimination of urolithiasis were noted, 37.5% preserved until now a normal renal function and 62.5% of them reached ESRD at the median age of 55.8 ± 12.31 years old. In this study 33-34InsC mutation gives a controversial clinical effect in children and adults. The implication of other genetic and/or environmental factors can play a crucial role in determining the ultimate phenotype.

Metformin and aerobic exercise are routinely co-prescribed in the management of metabolic syndrome, yet evidence regarding their interaction on cardiorespiratory fitness and substrate oxidation adaptations remains inconsistent. This study aimed to investigate the effects of combined metformin and aerobic training on peak oxygen uptake (VO₂peak), maximal fat oxidation (MFO), submaximal substrate utilization, and perceived exertion in metformin-naïve adults with metabolic syndrome. In this randomized, placebo-controlled trial, 24 metformin-naïve adults with metabolic syndrome were allocated to receive either metformin (1000 mg/day; MET-EX) or a matched placebo (PLA-EX) combined with supervised aerobic training (5 sessions/week, 60% VO₂peak, 500 kcal/session) for five weeks; 22 participants (n = 11 per group) completed the protocol. VO₂peak, MFO, fat and carbohydrate oxidation, energy expenditure, and rating of perceived exertion (Borg 6–20) were assessed before and after the intervention. The absolute VO₂peak gain was modestly attenuated in MET-EX relative to PLA-EX (group × time interaction p = 0.042; +0.11 vs. +0.26 L·min⁻¹), whereas the interaction for relative VO₂peak did not reach significance (p = 0.088). In contrast, MFO increased substantially more in MET-EX than in PLA-EX (+0.13 vs. +0.04 g·min⁻¹; p = 0.001), accompanied by greater fat oxidation, energy expenditure, and perceived exertion during moderate-to-high submaximal exercise intensities. Moreover, VO₂peak improvement was negatively correlated with age exclusively in MET-EX (r = −0.87, p < 0.001). These findings suggest that metformin induces a dissociated adaptation profile during aerobic training in metabolic syndrome, characterized by enhanced lipid oxidation alongside attenuated cardiorespiratory adaptations and greater perceived effort, particularly in older individuals.