Spectrum of Organic Aciduria Diseases in Tunisia: A 35-year Retrospective Study.

Background: Organic aciduria diseases (OADs) occur worldwide, with differences in prevalence and patterns between populations. Objectives: To describe the spectrum of OADs identified in Tunisia over a 35-years period. Materials and Methods: This retrospective study included patients who were diagnosed with OADs between 1987 and 2022 in the Laboratory of Biochemistry, Rabta Hospital, Tunisia. Organic acids were analyzed using gas chromatography-mass spectrometry. Results: A total of 30,670 urine samples were analyzed for OADs, of which 471 were positive for OADs. The estimated incidence of OADs in Tunisia was 6.78 per 100,000 live births. Methylmalonic (n = 146) and propionic (n = 90) acidurias were the most common OADs (estimated incidence: 2.10 and 1.30 per 100,000 live births, respectively). There were 54 cases of L-2-hydroxyglutatric acidurias and 30 cases of pyroglutamic acidurias, which makes it one of the highest in the world. The main clinical features were hypotonia (65%) and feeding difficulties (41%). Age at diagnosis was highly variable, ranging from 1 day to 49 years. Only 27% of the patients were diagnosed within the first month of life. The prevalence of OADs was highest in the Center-East and Southeast regions. Conclusions: In Tunisia, OADs are relatively frequent, but there are shortcomings regarding the diagnosis of these disorders. The frequency and health/social impact of these disorders warrant the need for implementing newborn screening programs and suitable patient management.

Anti Mullerian hormone as a diagnostic tool for polycystic ovary syndrome in women of reproductive age with morbid obesity.

OBJECTIVES: The aim of the study was to analyze the performance of the anti-mullerian hormone (AMH) level for the diagnosis of polycystic ovary syndrome in women with morbid obesity. STUDY DESIGN: A single-centre cross-sectional study was conducted in 50 women of reproductive age with a body mass index (BMI) ≥ 40 kg/m2. Each patient underwent a clinical examination, biological and hormonal assays, and an ovarian ultrasound between the third and the fifth day of the menstrual cycle. Polycystic ovary syndrome was diagnosed according to the Rotterdam's criteria. RESULTS: The mean age of participants was 34.2 ± 7.5 years. Polycystic ovary syndrome was diagnosed in 20 women (40%). Age and anthropometric parameters did not differ between women with and without polycystic ovary syndrome. The mean AMH level was significantly higher in women with polycystic ovary syndrome (3.4 ± 3.6 vs 1.3 ± 1.2 ng/ml, p=0.010). It was positively correlated with the Ferriman and Gallwey score (r=0.496, p=0.016), total testosterone level (r=0.524, p < 10-3) and the LH/FSH ratio (r=0.290, p=0.046). In women aged between 35 and 45 years, the optimum cut-off level for the diagnosis of polycystic ovary syndrome was 0.81 ng/mL, providing a sensitivity and a specificity of 90 and 71%, respectively with an area under the ROC curve of 0.857. CONCLUSIONS: AMH level was significantly higher in morbid obese women with polycystic ovary syndrome compared with those without polycystic ovary syndrome. Specific thresholds for this population must be assessed to improve the sensitivity and specificity of AMH for the diagnosis of polycystic ovary syndrome.

Low Plasma 25-Hydoxyvitamin D at Diagnosis Predicts Poor Outcomes in Patients with Bladder Cancer: A Prospective Cohort Study.

This study aimed to investigate whether plasma 25-hydroxyvitamin D (25-OHD) at diagnosis predicts poor outcomes in patients with urothelial bladder cancer. A total of 177 patients with non-muscle-invasive bladder cancer (NMIBC) were prospectively followed up over a period extending beyond 6 years. Data on poor outcomes (ie., recurrence, progression, and mortality) were collected. Plasma 25-OHD was measured by immunoassay. Cutoff-Finder web application was used to determine the best 25-OHD cutoff point to predict a specific poor outcome. Cox-hazard models were applied to test how plasma 25-OHD affect patients outcome while adjusting for potential confounding factors. During the follow-up period, tumor recurrence and progression occurred in 40.7% and 14.1% of patients, respectively and 11.3% of patients died. Baseline 25-OHD was lower in patients who experienced poor outcome (12.2 ± 7.44 vs. 16.7 ± 10.6 ng/mL; p < 0.001). Multi-adjusted HR (95% CI) for vitamin D deficiency (25-OHD < 12 ng/mL) was 2.09 (1.27-3.44) for recurrence, 2.63 (1.06-6.49) for progression and 2.93 (1.04-8.25) for mortality in patients with NMIBC. Low plasma 25-OHD in NMIBC patients is associated with higher risk of poor outcome. Future work is required to test whether correction of vitamin D deficiency will improve quality of life and extend survival in these patients.

Matrix metalloproteinase-7 could be a predictor for acute inflammation in psoriatic patients.

PURPOSE: The pathogenesis of psoriasis is characterized by a disruption of extracellular matrix (ECM) in which matrix metalloproteinases (MMPs) participate actively. We aimed to determine MMP-7 level and its association with the inflammatory response in order to determine its usefulness as a biomarker for psoriasis prediction. We also aimed to determine its distribution in uninvolved and involved psoriatic skin to evaluate the probable role of MMP-7 in psoriasis pathogenesis. MATERIALS AND METHODS: We recruited 108 psoriatic patients and 133 healthy controls. MMP-7, tissue inhibitors of metalloproteinases (TIMPs) and interleukin-6 (IL-6) levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA) assay. MMP-7 expression was detected by Immunohistochemistry (IHC) study. RESULTS: ECM turnover and inflammatory biomarker levels were significantly higher in psoriatic patients. MMP-7 revealed to be independently associated to psoriasis even after adjustment for different models. The area under the curve (AUC) of MMP-7 and inflammation Z-score were similar. MMP-7 was positively correlated with IL-6 and inflammation Z-score. Psoriasis severity (PASI) was correlated significantly with IL-6 (p = 0.007). The MMP-7 expression was detected in the epidermis of involved and uninvolved psoriatic skin. In involved skin, MMP-7 was expressed by basal and mostly suprabasal keratinocytes. In uninvolved skin, expression of MMP-7 was restricted to basal keratinocytes. CONCLUSION: MMP-7 is independently associated to psoriasis disease and to inflammatory response which make it a potential biomarker for this dermatosis.

Plasma 25-Hydroxyvitamin D Level at Admission Predicts Unfavorable Outcome in Intensive Care Unit Patients.

INTRODUCTION: Patients in intensive care units (ICUs) are at high risk of unfavorable outcomes. Considering the role of vitamin D (Vit D) in cardiovascular and immune functions, Vit D deficiency could affect ICU patients' outcomes. This study aimed to evaluate Vit D status and its predictive value for outcome in ICU patients. PATIENTS AND METHODS: A total of 169 ICU patients were followed during ICU stay. Primary outcome was the occurrence of at least one major adverse event; secondary outcomes were organ failure, septic shock, ICU-acquired infection, other adverse events, and ICU mortality. Plasma 25-hydroxyvitamin D (25(OH)D) was assessed by immunoassay. Multivariate Cox regression analyses were performed to test the associations of low 25(OH)D levels with poor outcomes. RESULTS: Around 75% of patients had 25(OH)D levels <12 ng/ml. During their ICU stay, 114 patients experienced a major adverse event, 85 patients presented an ICU-acquired infection, and 22 patients died. Plasma 25(OH)D levels <12 ng/ml were associated with higher risk of major adverse events, Hazard ratio [95% CI], 4.47 [1.77, 11.3], p = .020, and ICU-acquired infection, 2.67 [1.01, 7.42], p = .049, but not with increased risk of ICU mortality. CONCLUSIONS: Hypovitaminosis D is very common in ICU patients. Results of the present study show that low plasma 25(OH)D levels are associated with increased risk of unfavorable outcomes in these patients. Additional research is needed to investigate the impact of Vit D status and effect of Vit D supplementation in ICU patients.

Association of systemic beta-defensin-1 and -20G/A DEFB1 gene polymorphism with Behçet's disease.

BACKGROUND: Behçet's disease (BD) is a multisystem inflammatory disease of unknown etiology. Beta-defensins are antimicrobial peptides involved in epithelial host defense. To explore whether beta-defensins might be involved in BD pathogenesis, we examined plasma human beta-defensin-1 (hBD-1) and DEFB1 -20G/A polymorphism in BD patients. METHODS: This case-control study included 106 BD patients fulfilling the criteria of the International Study Group for BD and 156 controls. The -20G/A genotypes were determined by PCR-RFLP analysis in all participants, and plasma hBD-1 was assessed by ELISA in 77 BD patients and 44 controls, only. Stepwise multiple regression models were applied to determine independent predictors for plasma hBD-1 in BD patients. RESULTS: Distribution of -20G/A genotypes was different between BD patients and controls. Compared to GG genotype, "GA" genotype [OR (95% CI), 3.12 (1.56-6.16); p = .001] and "AA" genotype [2.57 (1.10-5.96); p = .027)] were associated with increased risk for BD. Plasma hBD-1 concentrations were significantly higher in BD patients than controls (9.81 ±â€¯3.52 ng/mL vs. 5.30 ±â€¯3.02 ng/mL; p < .001), and in BD patients with neurological involvement than those without (11.1 ±â€¯4.12 ng/mL vs. 9.19 ±â€¯3.10 ng/mL; p = .040). No variation was noted according to other clinical features, treatment received or -20G/A genotypes. In multivariate analysis, neurological involvement was the only predictor for plasma hBD-1 (ß, 0.274; p = .029). CONCLUSIONS: Findings suggest that hBD-1 and its encoding gene DEFB1 could modulate the risk for BD, especially for BD neurological involvement. Further work is needed for a better understanding of role of hBD-1 and its genetic variants in the pathogenesis of BD.

Bladder Cancer is Associated with Low Plasma 25-hydroxyvitamin D Concentrations in Tunisian Population.

Little evidence suggests an impact of vitamin D on bladder cancer risk in Caucasians. This study aimed to investigate association of plasma 25-hydroxyvitamin D (25-OHD) with urothelial bladder cancer (UBC) risk in Tunisians. A case-control study included 250 patients with UBC and 250 healthy controls. Plasma 25-OHD was assessed by a competitive chemiluminescence immunoassay. Vitamin D deficiency and insufficiency were defined as 25-OHD <30 nmol/L and 30 to 49.99 nmol/L, respectively. Logistic regression models adjusting for gender, age, smoking status, duration of smoking, occupational exposure, and season were applied. Vitamin D deficiency (50.4% vs. 34.8%; P < 0.001) and insufficiency (40.4% vs. 26.8%; P < 0.001) were more frequent in patients than controls. Multivariate analysis showed that UBC is associated with vitamin D deficiency [odd-ratio (95% confidence interval), 3.71 (1.76-7.80); P = 0.001] and vitamin D insufficiency [2.65 (1.40-5.01); P = 0.003]. Other predictors of UBC were female gender, tobacco use, smoking duration, and occupational exposure. Plasma 25-OHD concentrations are low in Tunisian patients with UBC. These findings support experimental and epidemiological evidence of protective role of vitamin D against UBC but could not ascertain causal relationship. Further prospective studies and clinical trials are warranted to check causality.

Plasma total homocysteine: usual values and main determinants in adults living in the Great Tunis region.

BACKGROUND: Elevated total plasma homocysteine (tHcy) is an established risk factor for occlusive vascular disease and is thought to increase the risk of pregnancy loss, birth defects, and cognitive impairment in the elderly. OBJECTIVES: To determine tHcy standard values and the prevalence of hyperhomocysteinemia (HHC) and to examine their association with demographic and life style factors in the Greater Tunis population. METHODS: This cross-sectional study included 2712 subjects (1228 males and 1484 females) aged 35 - 70 years, living in the Greater Tunis region. tHcy was analyzed by a fluorescent polarizing immunoassay method. HHC was considered as tHcy > or = 15 micromol/L. RESULTS: HHC was observed in 23.7% of subjects. Plasma tHcy was higher in males than females (median (5th - 95th percentile): 13.5 [8.75 - 26.3] micromol/L vs. 10.7 [6.94 - 19.6] micromol/L). The tHcy concentration was significantly increased in smokers, alcoholics, in subjects with vitamin B12 and folate deficiencies, and hyperuricemia. In multivariate analysis, HHC was associated with male gender, vitamin B12 deficiency, clearance of creatinine, alcohol consumption, and hyperuricemia. CONCLUSIONS: HHC is common in Tunisian adults. Male gender, advanced age, renal insufficiency, low vitamin B12 status, hyperuricemia, and alcohol consumption are the main determinants of HHC in this population.

Dyslipidemia in the Greater Tunis population: prevalence and determinants.

BACKGROUND: Economic development and socio-demographic changes have led to increased frequency of cardiovascular disease and other chronic diseases in Tunisia. OBJECTIVES: To assess the prevalence of different types of dyslipidemia and to examine their association with sociodemographic characteristics in the Greater Tunis population. METHODS: The study included 2712 subjects (1228 men and 1484 women) aged 35-70 years, recruited during the years 2004 and 2005 from the Greater Tunis population. Hypercholesterolemia, hypertriglyceridemia, and low HDL cholesterol were defined according to the National Cholesterol Education Program-Adult Treatment Panel III. RESULTS: The prevalence of hypercholesterolemia, hypertriglyceridemia, and low HDL cholesterol was 40.8% (34.9% in males and 45.8% in females; p < 0.001), 29.2% (31.1% in males and 27.6% in females; p < 0.05), and 21.2% (32.5% in males and 11.5% in females; p < 0.001), respectively. The prevalence was higher in urban than rural regions. Hypercholesterolemia was more frequent in illiterate women and in men with high education level. CONCLUSIONS: Dyslipidemias are common in Tunisians, mainly in urban areas, in illiterate women as well as in men with high levels of education. Profound changes of life style and dietary habits of Tunisians are needed to reduce the risk of cardiovascular diseases.

[Erythrocyte abnormalities in thyroid dysfunction]. / Les anomalies ertyrocytaires au cours des dysthyroïdies.

BACKGROUND: Erythrocyte abnormalities are frequently associated with thyroid dysfunction. However, they are rarely investigated and related to the thyroid. AIM: This study was aimed to determine the nature and frequency of erythrocyte abnormalities in thyroid disease and look for their evolution after thyroid function restoration. METHODS: This retrospective study included 412 patients with peripheral thyroid disease; hyperthyroidism (n=235) or hypothyroidism (n=177). Hyperthyroidism was considered for TSH<0.10 ÌUI/ml and hypothyroidism for TSH>5.0 ÌUI/ml. Anemia was defined by hemoglobin level<13 g/dl in men and <12 g/dl in women, microcytosis by mean corpuscular volume (MCV)<80 fl, macrocytosis by MCV>98 fl, and hypochromia by mean corpuscular hemoglobin (MCH)<25 pg. Restoration of euthyroid state was considered in patients with normal TSH levels for at least 3 months. RESULTS: Anaemia was observed in 40.9% of patients with hyperthyroidism and 57.1% of patients with hypothyroidism. Among these, normocytic or macrocytic anaemia was present in 46.3% of cases. Whereas, microcytosis, with or without anaemia, was noted in 87.7% of patients with hyperthyroidism. FT4 was positively correlated with the number of red blood cells and haemoglobin, and inversely correlated with MCV and MCH. After restoration of euthyroid state, most erythrocyte abnormalities were corrected. CONCLUSION: Thyroid diseases are frequently associated with erythrocyte abnormalities, including normocytic anaemia in hypothyroidism and microcytosis in hyperthyroidism. These abnormalities should be investigated and corrected. Their presence could steer towards subclinical thyroid dysfunction, allowing its early management.

[Minor beta thalassemia masked by a hemoglobin A2 mutant]. / Une bêta thalassémie mineure masquée par un mutant de l'hémoglobine A2.

BACKGROUND: The elevation of hemoglobin A2 (HbA2) is an essential criterion in the diagnosis of minor ss thalassemia. AIM: To report a case of minor ss thalassemia HbA2 with normal HbA2 rate. OBSERVATION: We report the case of ten years old boy, with hypochromic microcytic anemia, refractory to iron treatment. The study of hemoglobin (Hb) has revealed the presence of a minor abnormal fraction of Hb, amounted to 2.8%, associated with the presence of HbF and normal levels of HbA2. Family study revealed the presence of two Hb abnormalities (ss thalassemia trait and HbA2 mutant) transmitted to offspring in isolation or associated. The genotypic study confirmed the presence of minor, 0 thalassemia and a °/00 gene mutation, causing a new mutant HbA2 named HbA2 Pasteur-Tunis [°/00 59(E3)LysgAsn(AAGgAAC)]. CONCLUSION: The presence of °/00 mutant reduces HbA2 level and could hide ss thalassemia trait. Rigorous and methodical interpretation of phenotypic data is crucial to not overlook the presence of ss thalassemia trait, whose diagnosis is crucial for genetic counseling and prenatal diagnosis.

Predictors for cardiovascular morbidity and overall mortality in Tunisian ESRD patients: a six year prospective study.

OBJECTIVES: The study was aimed to test the predictive value of several potential cardiovascular factors and markers for non fatal cardiovascular events (CVE) and overall mortality in Tunisian patients with renal failure. SUBJECTS AND METHODS: One hundred and fifteen renal failure patients were followed-up from 2000 to 2006. At enrollment, each patient underwent clinical examination and blood collection for analysis of lipid parameters, albumin, C reactive protein (CRP), parathyroid hormone (PTH), homocysteine and hemoglobin. Multivariate Cox regression models were applied to identify the predictors for non fatal CVE and overall mortality. RESULTS: During the follow up, seventeen patients were lost. Among the 98 remaining patients, 29 presented a non fatal CVE (21.5%) and 15 were deceased (11.1%). In univariate analyses, non fatal CVE were more frequent in smokers and in patients with high PTH concentrations and low HDL levels. Moreover, low albumin concentrations were univariately associated with overall mortality. In the multivariate analysis, non fatal CVE was significantly and independently associated with age [hazard ratio (95% confidence interval), 1.04 (1.01-1.08); p=0.028] and the upper quartile of PTH concentrations [2.68 (1.24-5.81); p=0.013]. Overall mortality was independently predicted by the bottom quartile of albumin concentrations [5.62 (2.02-15.6); p=0.001] and the upper quartile of CRP concentrations [3.20 (1.14-8.79); p=0.027]. CONCLUSION: Advanced age and high PTH levels are the main predictors of CVE, whereas low albumin and high CRP concentrations are the independent predictors of death in Tunisian renal patients. A better control of these factors would greatly increase the patient's survival rates.