Maternal 25-hydroxyvitamin D level and the occurrence of neural tube defects in Tunisia.

OBJECTIVE: To determine whether low vitamin D levels in pregnant women are associated with the occurrence of neural tube defects (NTDs) in Tunisia. METHODS: In a prospective study, pregnant women were recruited at a center in Tunis between January 1, 2012, and December 30, 2013. Women carrying a fetus with a severe NTD were recruited before elective termination. Matched, healthy pregnancy women were enrolled into a control group. Plasma levels of 25-hydroxyvitamin D were measured by a competitive chemiluminescence immunoassay. RESULTS: Overall, 68 women formed the NTD group and 64 the control group. The mean maternal vitamin D level was significantly lower in the NTD group (20.65±10.25nmol/L) than in the control group (28.30±13.82nmol/L; P<0.001). Vitamin D deficiency was recorded for 53 (78%) women in the NTD group and 39 (61%) in the control group. Vitamin D insufficiency was recorded for 15 (22%) women in the NTD group and 20 (31%) in the control group. Vitamin D sufficiency was found only in the control group (n=5 [8%]; P<0.001). CONCLUSION: The findings confirm an association between a decreased vitamin D level in pregnant women and the risk of fetal NTDs.

Phenotypic variability in a Tunisian family with X-linked adrenoleukodystrophy caused by the p.Gln316Pro novel mutation.

INTRODUCTION: X-linked adrenoleukodystrophy is a neurodegenerative recessive disorder that affects the brain white matter and associated with adrenal insufficiency. It is characterized by an abnormal function of the peroxisomes, which leads to an accumulation of the Very Long Chain Fatty Acids (VLCFA) in plasma and tissues, especially in the cortex of the adrenal glands and the white matter of the central nervous system. Mutations in the ABCD1 gene affect the function of the encoded protein ALDP, an ATP-binding cassette transporter located in the peroxisomal membrane protein. PATIENTS AND METHODS: The present study reports the clinical, biochemical and molecular investigation in a Tunisian family with two affected males with childhood cerebral adrenoleukodystrophy. RESULTS: The ABCD1 gene sequencing indicated a novel hemizygous missense mutation c.947A>C (p.Gln316Pro) in the exon 2 of the ABCD1 gene in the patients, their mother and their sisters. This missense variation was predicted to be possibly damaging by the PolyPhen and SIFT prediction software. Although presence of the same mutation c.947A>C in both siblings, they present different clinical signs. CONCLUSIONS: Based on the disease's progress, the clinical signs and biochemical aspects between the two siblings, we demonstrate that there is no correlation genotype-phenotype.

Association of maternal homocysteine and vitamins status with the risk of neural tube defects in Tunisia: A case-control study.

BACKGROUND: This study was conducted to determine whether low folate and vitamin B12 levels, as well as high homocysteine levels in pregnant women are associated with neural tube defects (NTDs) in Tunisia. METHODS: A total of 75 NTDs pregnancies and 75 matched controls were included in the study. Their vitamin B12, folate, and red blood cell folate concentrations were measured using a radio-immunoassay kit and total homocysteine concentrations were determined using a fluorescent polarization immunoassay. RESULTS: Vitamin B12 and folate concentrations were lower in NTD-affected pregnant women than in controls (respectively, p = 0.009 and p < 0.001). Total homocysteine concentration was significantly higher in the NTDs group than in controls (p = 0.008). In the case group, the folate levels were positively related with vitamin B12 levels (r = 0.54; p < 0.001) and negatively correlated with total homocysteine levels (r = -0.19; p = 0.04). Besides, red blood cell folate levels were positively correlated with folate levels (r = 0.24; p = 0.02) and negatively correlated with total homocysteine levels (r = -0.37; p = 0.001). CONCLUSION: Lower concentrations of folate and vitamin B12 are related to the increased risk of NTDs. Both folate and vitamin B12 intake insufficiency could contribute to the increased risk of NTDs. A dietary supplement, combining folate and vitamin B12, might be an effective measure to decrease the NTDs incidence in Tunisia.

Association of MTHFR A1298C polymorphism (but not of MTHFR C677T) with elevated homocysteine levels and placental vasculopathies.

Our aim in this study was to investigate the association between elevated homocysteine levels and the two MTHFR polymorphisms, C677T and A1298C, with several pregnancy complications such as recurrent pregnancy loss, preeclampsia, placental abruption and intrauterine growth retardation. In 203 women with different placental vasculopathies, we determined the MTHFR C677T and the A1298C prevalence and their relative association to elevated homocysteine levels. The mean plasma homocysteine level was significantly higher in the pathologic groups when compared with the control group. We identified the carriage of the MTHFR A1298C polymorphism as a significant risk factor for vascular-related pregnancy complications. Women with MTHFR A1298C polymorphism or elevated homocysteine levels have an increased risk of placental vasculopathies. The MTHFR A1298C mutation also had a positive impact on elevated homocysteine levels. The lack of association between the MTHFR C677T polymorphism and pregnancy morbidities needs further studies.

Plasma homocysteine in schizophrenia: determinants and clinical correlations in Tunisian patients free from antipsychotics.

The existence of association between hyperhomocysteinaemia (HHC) and schizophrenia has been suggested by several recent studies. This study aimed to determine the prevalence of HHC and its main determinants, and sought a correlation with clinical features in Tunisian patients with schizophrenia. Plasma homocysteine (Hcy), folate, and vitamin B12, as well as the C677T methylene tetrahydrofolate reductase (MTHFR) polymorphism, were studied in 33 patients with schizophrenia, all free from antipsychotic treatment, and 35 age- and smoking-habit-matched healthy subjects as controls. Biochemical determinations and psychometric evaluations were carried out in patients before the administration of antipsychotics. The prevalence of HHC was higher and plasma B12 vitamin was significantly lower in patients. There was no significant difference in genotypic distribution and allelic frequency of the C677T MTHFR polymorphism between groups. Hcy was significantly correlated to the 'anhedonia-asociality' subscales of the Scale for the Assessment of Negative Symptoms (SANS). This study showed an association between HHC and schizophrenia, especially with the negative symptoms of the disease. In the Tunisian population, HHC in schizophrenia seems to be linked to vitamin B12 deficiency, likely caused by a lack of dietary animal proteins.