Primary membranoproliferative glomerulonephritis in Sfax, Tunisia: epidemiologic profile and prognostic factors.

INTRODUCTION: membranoproliferative glomerulo nephritis (MPGN) is a rare kidney disease with a poor prognosis as 50% of patients attend the end stage renal failure after 10 years of follow up. Several factors have been described associated with poor renal prognosis. The aim of our study is to determine the epidemiologic profile and to identify prognostic factors of MPGN. METHODS: our study is retrospective over a period of 16 years (January 1996 - December 2011) including all cases of primary MPGN aged more than 15 years, collected at the nephrology department of Hedi Chaker University Hospital, Sfax, Tunisia. RESULTS: we collected 118 cases of primary MPGN, with mean age of 45 (SD 19) years. The incidence of MPGN has decreased from 10 cases/year between 1996 and 1999 to 5 cases/year between 2008 and 2011. Seventy-nine percent of patients (n=93) had renal failure at the moment of diagnosis (e-GFR less than 60 ml/min/1.73m2;). After a mean follow-up of 51.9 (SD 44) months, progression to end stage renal failure was observed in 43.5% of followed cases (n=20). On univariate analysis, factors associated with death or progression to end stage renal failure were initial renal failure and sclerotic glomeruli (respectively p at 0.040 and 0.032). Multivariate analysis indicated that initial renal failure was significantly correlated with death or progression to end stage renal failure (HR: 0.14, 95% CI (0.033-0.593), p=0.008). CONCLUSION: there has been a decline in the number of cases of MPGN diagnosed in our hospital. The presence of renal failure at diagnosis was associated with death or progression to end stage renal failure.

[Pregnancy in patients on chronic haemodialysis: about 25 cases which occurred in the south of Tunisia]. / La grossesse en hémodialyse chronique: à propos de 25 cas survenus dans le Sud Tunisien.

INTRODUCTION: the occurrence of pregnancy in patients on chronic haemodialysis is rare. However, given the evolution in dialysis technique, improvement in fertility is possible. The purpose of our study was to report our experience concerning the occurrence of pregnancy in patients on dialysis and to identify factors involved in its success. METHODS: we conducted a retrospective study on 25 spontaneous pregnancies occurred in 19 patients treated with periodical hemodialysis in different hemodialysis centers in the south of Tunisia over a period of 34 years. RESULTS: maternal age at the onset of pregnancy was, on average, 35.6 years [23-44 years] with an average seniority in hemodialysis of 4.22 years [1-17 years]. Seven patients (37%) had residual diuresis (>500 ml/24h). The prescribed weekly number of hours of dialysis was ≥16 hours per week in 7 cases and ≥20 hours in 4 cases. Success of pregnancy (new-born surviving at least 28 days) was estimated at 56%. The median gestational age was 34 weeks of amenorrhea [28-38 WA]. The average neonatal weight was equal to 1970g [1500g-2300g]. Analytical study showed a significant correlation between the increase in the hours of dialysis per week and the success of pregnancy (R=0.59; p=0.002). CONCLUSION: it was noted that with adequate support and in particular, increasing the number of sessions of dialysis, materno-fetal complications can be minimized and the balance risk-benefit can turn the chance for a woman on dyalisis to become pregnant.

A novel disease-causing mutation in the Renin gene in a Tunisian family with autosomal dominant tubulointerstitial kidney disease.

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare group of disease that affect the tubules of the kidney. There are 4 known subtypes of ADTKD classified based on causative genes and clinical features. In our study, we aimed to identify the causative subtypes of ADTKD in a Tunisian ADTKD family (3 affected members), in whom standard nephrological diagnosis did not provide clear subtype of ADTKD, until genetic testing was performed. Sanger sequencing was performed for UMOD, HNF1ß and REN genes. Mutational analysis allowed us to detect a heterozygous mutation in the REN gene: c.1172C > G, (p.T391R) in exon 10. In silico analyses predicted that the novel likely pathogenic mutation affect protein stability and 3D structure. Our study highlights the importance of establishing a genetic diagnosis to identify the subtype of ADTKD for better patient care. To the best of our knowledge, we report here a first Tunisian ADTKD-REN family.

A novel de novo splicing mutation c.1444-2A>T in the TSC2 gene causes exon skipping and premature termination in a patient with tuberous sclerosis syndrome.

Tuberous sclerosis complex (TSC) syndrome is a neurocutaneous syndrome that affects the brain, skin, and kidneys that has an adverse impact on the patient's health and quality of life. There have been several recent advances that elucidate the genetic complex of this disorder that will help understand the basic neurobiology of this disorder. We report a Tunisian patient with clinical manifestations of TSC syndrome. We investigated the causative molecular defect in this patient using PCR followed by direct sequencing. Subsequently, in silico studies and mRNA analysis were performed to study the pathogenicity of the new variation found in the TSC2. Bioinformatics tools predicted that the novel mutation c.1444-2A>T have pathogenic effects on splicing machinery. RT-PCR followed by sequencing revealed that the mutation c.1444-2A>T generates two aberrant transcripts. The first, with exon 15 skipping, is responsible for the loss of 52 amino acids, which causes the production of an aberrant protein isoform. The second, with the inclusion of 122 nucleotides of intron 14, is responsible for the creation of new premature termination codons (TGA), which causes the production of a truncated TSC2 protein. This study highlighted the clinical features of a Tunisian patient with TSC syndrome and revealed a splicing mutation c.1444-2A>T within intron 14 of TSC2 gene, which is present for the first time using Sanger sequencing approach, as a disease-causing mutation in a Tunisian patient with TSC syndrome.

[Epidemiological profile of terminal chronic renal failure in the region of Sfax]. / Profil épidémiologique de l'insuffisance rénale chronique terminale dans la région de Sfax.

INTRODUCTION: Terminal chronic renal failure is a truly global public health problem. In 2011, the cost of management of patients on dialysis has surpassed 90 million dinars (37.000 euro) in Tunisia, nearly 5% of the overall health spending. A better knowledge of the epidemiological profile of terminal chronic renal failure contributes to the implementation and evaluation of health strategies aimed to improve prevention and disease management. This study aimed to describe the epidemiological profile of incident cases in the Sfax Governorate over the period of 10 years. METHODS: We conducted a descriptive retrospective study over the period from January 2003 to December 2012. The incident cases of terminal chronic renal failure in the Sfax Governorate were included in the study. RESULTS: The diagnosis of terminal chronic renal failure was made in 1708 cases: 957 men and 751 women (sex-ratio = 1.27). The average age was 58.4 years [10-100 years]. The study of the evolution of the average age during the study period showed a tendency to increase with positive correlation coefficient (0.749) and p = 0.006. The main causal nephropathy was diabetic nephropathy (21.5%), with a significant increase in its frequency from one year to the other (positive correlation coefficient (0.770) with p = 0.009). Hemodialysis was the dialysis technique of choice, performed in 96% of patients. CONCLUSION: A national registry is indispensable in order to better understand the epidemiological profile of terminal chronic renal failure in Tunisia and to improve its management.

Mutational analysis in patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD): Identification of five mutations in the PKD1 gene.

Autosomal Dominant Polycystic Kidney Disease (ADPKD), the most frequent genetic disorder of the kidneys, is characterized by a typical presenting symptoms include cysts development in different organs and a non-cysts manifestations. ADPKD is caused by mutations in PKD1 or PKD2 genes. In this study, we aimed to search for molecular causative defects among PKD1 and PKD2 genes. Eighteen patients were diagnosed based on renal ultrasonography and renal/extra-renal manifestations. Then, Sanger sequencing was performed for PKD1 and PKD2 genes. Multiplex Ligation dependent Probe Amplification method (MLPA) methods was performed for both PKD genes. Mutational analysis of the PKD2 gene revealed the absence of variants and no deletions or duplications of both PKD genes were detected. But three novels mutations i.e. p.S463C exon 7; c. c.11156+2T>C IVS38 and c.8161-1G>A IVS22 and two previously reported c.1522T>C exon 7 and c.412C>T exon 4 mutations in the PKD1 gene were detected. Bioinformatics tools predicted that the novel variants have a pathogenic effects on splicing machinery, pre-mRNA secondary structure and stability and protein stability. Our results highlighted molecular features of Tunisian patients with ADPKD and revealed novel variations that can be utilized in clinical diagnosis and in the evaluation of living kidney donor. To the best of our knowledge, this is the first report of Autosomal Polycystic Kidney Disease in Tunisia.

[Post-streptococcal glomerulonephritis in the south of Tunisia: A 12-year retrospective review]. / La glomérulonéphrite aiguë post-streptococcique de l'enfant dans le sud tunisien : étude rétrospective de 12 ans.

AIM: Post-streptococcal glomerulonephritis (PSGN) is a frequent cause of acute nephritis in children. This study aimed to describe the epidemiology, clinical characteristics and outcomes of PSGN and look for predictor's factors of severity. METHODS: A 12-year retrospective review of case notes and laboratory data was conducted at a department of pediatrics, pediatric emergency and intensive care, Hedi Chaker Hospital. RESULTS: One hundred seventy eight children were treated for PSGN with a mean age of 7.6 ans±3.43 ans. One hundred and forty-two patients (80%) had a history of a recent upper respiratory tract or skin infection. Streptococcal pharyngitis was the most common cause, identified in 113 patients (67.6%). Macroscopic hematuria and edema were noted in 135 (75.8%) and 114 cases (64%) respectively. Hypertension was present in 55 patients (31%). Oliguria was noted in 30 children (16.8%). Sixty-six subjects (37%) developed acute renal impairment (creatinine≥70 micromoles/L). No correlation was demonstrated between acute renal impairment and age, sex, triggering infection, anemia and white blood cell count. Creatinine greater than 56.35 micromoles/L was associated with a high risk of developing high blood pressure. The mean length of admission was 5.8 days±4.44. Only one subject has ongoing renal dysfunction. CONCLUSION: PSGN remains a common nephropathy in our region. The detection and effective treatment of any infection that may be involved can reduce the incidence of this disease.

Identification of compound heterozygous patients with primary hyperoxaluria type 1: clinical evaluations and in silico investigations.

BACKGROUND: Primary hyperoxaluria type 1 (PH1) is an autosomal recessive inherited disorder of glyoxylate metabolism in which excessive oxalates are formed by the liver and excreted by the kidneys. Calcium oxalate crystallizes in the urine, leading to urolithiasis, nephrocalcinosis, and consequent renal failure if treatment is not initiated promptly. Mutations in the AGXT gene which encodes the hepatic peroxisomal enzyme alanine:glyoxylate aminotransferase are responsible of PH1. In the present work, we aimed to analyze AGXT gene and in silico investigations performed in four patients with PH1 among two non consanguineous families. METHODS: Exhaustive gene sequencing was performed after PCR amplification of coding exons and introns boundaries. Bioinformatic tools were used to predict the impact of AGXT variants on gene expression as well as on the protein structure and function. RESULTS: Direct sequencing of all exons of AGXT gene revealed the emergence of multiple mutations in compound heterozygous state in the two studied families. Two patients were compound heterozygous for the c.731 T > C, c.32C > T, c.1020A > G and c.33_34insC and presented clinically with recurrent urinary tract infection, multiple urolithiasis and nephrocalcinosis under the age of 1 year and a persistent hyperoxaluria at the age of diagnosis. The two other patients presenting a less severe phenotypes were heterozygous for c.731 T > C and homozygous for the c.32C > T and c.1020A > G or compound heterozygous for c.26C > A and c.65A > G variants. CONCLUSION: In Summary, we provided relevance regarding the compound heterozygous mutations in non consanguineous PH1 families with variable severity.

Optimization of therapeutic drug monitoring of vancomycin in patients with chronic hemodialysis
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PURPOSE: To validate a simplified vancomycin monitoring algorithm in patients on chronic hemodialysis who required intravenous vancomycin for at least 3 weeks. MATERIALS AND METHODS: In this prospective study, all hemodialysis patients who were admitted between April 1, 2013, and March 31, 2015, in our unit for suspected or confirmed methicillin-resistant Staphylococcus aureus infection that required vancomycin were enrolled. All patients were categorized into two groups. In group 1 (standard vancomycin dosing algorithm), the maintenance doses of vancomycin were adjusted according to the pre-hemodialysis vancomycin concentrations determined before each hemodialysis session. In group 2 (simplified vancomycin dosing algorithm), pre-dialysis vancomycin trough levels were taken before the 2nd and the 6th session of hemodialysis. Maintenance doses were adjusted according to the residual concentrations of vancomycin. RESULTS: A total of 101 blood samples were collected, the average plasma concentration of vancomycin was 13.1 ± 3.8 µg/mL. 64 (63.4%) levels fell out of the therapeutic range. Seven (6.9%) of these exceeded the therapeutic range and 30 (29.7%) were lower. After the loading dose, the average plasma concentration was 11.2 ± 3.4 µg/mL. There were no statistically significant differences between the two groups with respect to the average plasma concentration of vancomycin and the proportion of vancomycin trough levels in the target range. CONCLUSION: The vancomycin dosing algorithm using limited concentration monitoring for hemodialysis patients achieved drug concentrations comparable to those found with more frequent monitoring and resulted in significant cost savings.
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Minimal change disease in horseshoe kidney.

The horseshoe kidney is a frequent urological birth defect. The most frequent complications are urinary tract infections, stones and hydronephrosis. The occurrence of glomerular disease in horseshoe kidney is rare. Therefore, we report the first case of minimal change disease occurring in a patient with horseshoe kidney in literature. A 22-year-old Caucasian man without personal or family medical history admitted to the pneumology department for a pulmonary artery embolism. In presence of a generalized oedema, a biological assessment was performed yielding intense nephrotic syndrome with urine protein excretion 22g/day. The abdominal ultrasound revealed a horseshoe kidney. Hence a scanno-guided kidney biopsy was taken yielding minimal change disease. High dose steroids were started, then gradually tapered with good response. Horseshoe kidney is the most common renal fusion anomaly, with a prevalence of 0.25% among the general population. The occurrence of glomerular nephropathy in horseshoe kidney has been reported in few cases. We report the first case of minimal change disease occurring in a patient with horseshoe kidney in literature. The mechanism of the association between the horseshoe kidney and these renal pathologies could not be explained in the previous reports. There is no literature data indicating a high rate of glomerulonephritis in horseshoe kidneys. The co-incidence of two renal diseases in this patient can be only a coincidence. The question that arises is whether this glomerulopathy is associated or not with this anatomical abnormality. Further studies are needed to answer this question.

Diet in chronic kidney disease in a Mediterranean African country.

BACKGROUND: Mediterranean diet is characterized by low to moderate consumption of animal protein and high consumption of fruits, vegetables, bread, beans, nuts, seeds and other cereals. It has been associated with reduced risk of cardiovascular disease. However, it is not suitable for chronic kidney disease because of high potassium intake. DISCUSSION: Tunisia is an emerging Mediterranean country with limited resources, a high prevalence of chronic hemodialysis treatment and high dialysis expenditures. In order to limit dialysis cost, primary and secondary prevention of chronic renal disease are of paramount importance. In addition to drugs, secondary prevention includes diet measures (e.g. salt diet, protein diet). The aims of diet practice in chronic kidney disease are to slow chronic renal failure progression and to prevent its complications like hyperphosphatemia and hyperkaliemiae. A few decades ago, a Tunisian diet was exclusively Mediterranean, and protein consumption was not excessive. However, today, protein consumption is more comparable to western countries. Salt consumption is also excessive. Some Tunisian diets still include food with high potassium intake, which are not suitable for patients with chronic kidney disease. Therefore, the role of the dietician is extremely important to help calculate and create a dietary regimen tailored to each of our patients. Advice about diets should be adapted to both the patient and population habits to improve adherence rate. As such, the purpose of this article is to provide our own experience regarding medical nutrition therapy in patients with chronic kidney disease in Tunisia, with some changes in food habits. Prevention is far better than treatment. In this perspective, dietary measures must be at the core of our intervention.

Quality of life in chronic hemodialysis patients:about 71 cases.

BACKGROUND: The chronic hemodialysis imposes various limitations on patients that may affect their quality of life. However, Tunisian studies on this matter remain scarce. AIMS: To assess the quality of life among hemodialysis patients and to identify the factors influencing their quality of life. METHODS: We performed a cross-sectional study which included 71 outpatients, during the month of January 2013, in the department of Nephrology at Hedi Chaker Sfax university hospital in Tunisia. We used the specific scale Kidney Disease Quality of Life Short-Form (KDQOL-SF™) to assess the patient's quality of life. This instrument combines the short form 36 health survey questionnaire (SF-36) and a specific module adapted to renal function. Regression analysis was used to adjust for confounding factors. RESULTS: The global average score, according to KDQOL-SF and the SF-36 were respectively 51.6 and 38.2. The QOL was impaired in 90% of the cases. The logistic regression identified six variables to be correlated with impaired QOL. These six factors in descending order of importance were:  lack of autonomy, a dialysis rhythm of thrice a week, an age over 60 years, a comorbid diabetes, low social economic level and living in rural areas. CONCLUSION: Our study highlights the high frequency of QOL impairment upon patients on hemodialysis underlining the interest of a systematic effort to assess the quality of life in those patients. It also shows the interest of acting upon modifiable factors correlated with the alteration of the quality of life. In this way, the professional integration of the patients should be favored as well as peritoneal dialysis.

[Sexual disorder in hemodialysis patients]. / Troubles sexuels chez le patient Hémodialysé.

OBJECTIVES: To identify the sexual problems, to assess their prevalence and to determine the various factors involved in their occurrence in patients on hemodialysis for at least 6 months. PATIENTS AND METHODS: Fifty hemodialysis patients consulting in the dialysis unit of the nephrology department of the University Hospital Hedi Chaker of Sfax (Tunisia), during the period from 1 June to 30 August 2012, were included in this study, The Hospital Anxiety and Depression Scale (HADS) was used to evaluate anxiety and depression. The patients' quality of life was assessed by Kidney Disease Quality of Life ¼ (KDQoL). RESULTS: Patients' mean age was 51.2 years. The average of hemodialysis period was 6,73 years. After the beginning of hemodialysis, 26% of patients were sexually inactive and 62% reported a decrease of their sexual activity. The prevalence of sexual dysfunction was 86.48%. Mean age of 55 years or greater was significantly correlated with risk of sexual disorders. These disorders were also positively correlated with personal medical history, some nephropathy data, a hemodialysis period greater than or equal to 1 year, depression, anxiety and impaired quality of life. CONCLUSION: The prevalence of sexual dysfunction in hemodialysis patients is high and many factors were involved in their occurrence. A collaborative effort between nephrologists, psychiatrists and sexologists before dialysis, seems to be essential.

Angiogenic activity in the sera of patients with post-kidney transplant erythrocytosis.

Post-kidney transplant erythrocytosis (PTE) is one of the hematological complications in the renal transplant patients. While its pathogenesis still remains to be elucidated completely, a number of therapies are available for the management of PTE. The aim of this prospective study was to investigate whether angiogenesis may be involved in the pathogenesis of post-transplant erythrocytosis by comparing its level with those of different classes of erythrocytosis [polycythemia vera (PV), idiopathic erythrocytosis and secondary erythrocytosis]. The angiogenic activity was evaluated by the assessment of the serum vascular endothelial growth factor (VEGF) levels, as one of circulating angiogenic factor, using a standardized enzyme-linked immunosorbent assay commercial kit in 13 PTE (2 F/11 M), in 75 untreated erythrocytosis non-transplant patients and in 21 healthy subjects controls. The results indicated that VEGF was overproduced in advanced and untreated PV patients and to a lesser degree in idiopathic erythrocytosis thus confirming an increased angiogenic activity. However, there is no evidence of increased angiogenesis in PTE and in secondary erythrocytosis. The absence of angiogenesis in PTE and its presence in PV is another argument that the pathogenesis of these two entities is different.

Ciprofloxacin-induced crystal nephropathy.

Ciprofloxacin is a commonly used antibiotic. Renal side effects are rare and are usually immune mediated. Clinical and experimental studies have suggested that crystalluria and crystal nephropathy occur in alkaline urine. Preexisting kidney function impairment, high dose of the medication, and advanced age predispose to this complication. We report a case of crystal nephropathy in a young woman treated with ciprofloxacin and a nonsteroidal anti-inflammatory drug.

Acute hemodialysis effects on doppler echocardiographic indices.

Conventional echocardiographic (ECHO) parameters of systolic and diastolic function of the left ventricular (LV) have been shown to be load dependent. However, the impact of pre-load reduction on tissue Doppler (TD) parameters of LV function is incompletely understood. To evaluate the effect of a single hemodialysis (HD) session on LV systolic and diastolic function using pulsed Doppler echocardiography and pulsed tissue Doppler imaging (TDI), we studied 81 chronic HD patients (40 males; mean age 52.4 ± 16.4 years) with these tools. ECHO parameters were obtained 30 min before and 30 min after HD. Fluid volume removed by HD was 1640 ± 730 cm³. HD led to reduction in LV end-diastolic volume (P <0.001), end-systolic volume (P <0.001), left atrium area (P <0.001), peak early (E-wave) trans-mitral flow velocity (P <0.001), the ratio of early to late Doppler velocities of diastolic mitral inflow (P <0.001) and aortic time velocity integral (P <0.001). No significant change in peak S velocity of pulmonary vein flow after HD was noted. Early and late diastolic (E') TDI velocities and the ratio of early to late TDI diastolic velocities (E'/A') on the lateral side of the mitral annulus decreased significantly after HD (P = 0.013; P = 0.007 and P = 0.008, respectively). Velocity of flow progression (Vp) during diastole was not affected by pre-load reduction. Pulmonary artery systolic pressure and the diameter of the inferior vena cava decreased significantly (P <0.001 and P <0.001, respectively) after HD. We conclude that most of the Doppler-derived indices of diastolic function are pre-load-dependent and velocity of flow progression was minimally affected by pre-load reduction in HD patients.

A homozygous missense mutation in the ciliary gene TTC21B causes familial FSGS.

Several genes, mainly involved in podocyte cytoskeleton regulation, have been implicated in familial forms of primary FSGS. We identified a homozygous missense mutation (p.P209L) in the TTC21B gene in seven families with FSGS. Mutations in this ciliary gene were previously reported to cause nephronophthisis, a chronic tubulointerstitial nephropathy. Notably, tubular basement membrane thickening reminiscent of that observed in nephronophthisis was present in patients with FSGS and the p.P209L mutation. We demonstrated that the TTC21B gene product IFT139, an intraflagellar transport-A component, mainly localizes at the base of the primary cilium in developing podocytes from human fetal tissue and in undifferentiated cultured podocytes. In contrast, in nonciliated adult podocytes and differentiated cultured cells, IFT139 relocalized along the extended microtubule network. We further showed that knockdown of IFT139 in podocytes leads to primary cilia defects, abnormal cell migration, and cytoskeleton alterations, which can be partially rescued by p.P209L overexpression, indicating its hypomorphic effect. Our results demonstrate the involvement of a ciliary gene in a glomerular disorder and point to a critical function of IFT139 in podocytes. Altogether, these data suggest that this homozygous TTC21B p.P209L mutation leads to a novel hereditary kidney disorder with both glomerular and tubulointerstitial damages.

Risk factors for acute decompensation of chronic kidney disease in hospitalized patients in the nephrology department: a case-control study.

OBJECTIVE: To investigate risk factors for acute kidney injury (AKI) in hospitalized patients with chronic kidney disease (CKD) a case-control study was conducted in the Nephrology Department of Hedi Chaker University Hospital in Sfax, Tunisia, for a 1-year period. METHODS: All patients with baseline renal insufficiency hospitalized for AKI were considered as cases. They were compared with control patients with CKD. A conditional logistic regression model was used to identify independent risk factors for AKI in patients with CKD. RESULTS: A total of 58 cases were compared with 114 control subjects. In multivariable models, baseline diabetes, cardiopathy disease, and exposure to non-steroidal anti-inflammatory drugs were independent risk factors for AKI in patients with CKD. However, exposure to calcium channel blockers (CCBs) was associated with decreased risk for AKI on CKD (OR = 0.4; CI 95%: 0.2 - 0.8, p = 0.007). CONCLUSIONS: Patients with CKD may benefit from more aggressive cardiovascular screening to prevent episodes of acute kidney injury. More efforts should be made to prevent prescription drug abuse and to demonstrate the role of CCBs in renal protection in these patients.

A double mutation in AGXT gene in families with primary hyperoxaluria type 1.

Primary hyperoxaluria type 1 (PH1) is a severe autosomal recessive inherited disorder of glyoxylate metabolism caused by mutations in the AGXT gene on chromosome 2q37.3 that encodes the hepatic peroxisomal enzyme alanine:glyoxylate aminotransferase. These mutations are found throughout the entire gene and cause a wide spectrum of clinical severity. Rare in Europe, PH1 is responsible for 13% of the end stage renal failure in the Tunisian child. In the present work, we identified the double mutation c.32C>T (Pro11Leu) and c.731T>C (p.Ile244Thr) in AGXT gene in five unrelated Tunisian families with PH1 disease. Our results provide evidence regarding the potential involvement of c.32C>T, originally described as common polymorphism, on the resulting phenotype. We also reported an extreme intrafamilial heterogeneity in clinical presentation of PH1. Despite the same genetic background, the outcome of the affected members differs widely. The significant phenotypic heterogeneity observed within a same family, with a same genotype, suggests the existence of relevant modifier factors.