Are treated celiac patients at risk for mycotoxins? An Italian case-study

Urinary biomarkers of mycotoxin exposure were evaluated in a group of celiac patients (n = 55) and in a control group of healthy subjects (n = 50) following their habitual diet. Deoxynivalenol (DON), zearalenone (ZEN), and fumonisin B1 (FB1) were monitored in 105 urinary samples collected from the two groups. Dietary habits were also recorded through compilation of a seven-day weighed dietary diary. Biomarkers of mycotoxin exposure were detected in 21 celiac patients and in 15 control subjects, corresponding to about 34% of total participants. In particular, ZEN was the most detected mycotoxin among all the studied subjects with a total of 19 positive cases. Results did not show a statistically significant difference in mycotoxin exposure between the two groups, and the presence of specific mycotoxins was not related to the intake of any particular food category. Our findings suggest little urgency of specific regulation for gluten free products, although the prevalence of exposure observed in free-living diets of both celiac and healthy subjects underlines the need of a constant surveillance on mycotoxins occurrence at large

Clinical, neuroradiological, and molecular characterization of mitochondrial threonyl-tRNA-synthetase (TARS2)-related disorder

PURPOSE: Biallelic variants in TARS2, encoding the mitochondrial threonyl-tRNA-synthetase, have been reported in a small group of individuals displaying a neurodevelopmental phenotype, but with limited neuroradiological data and insufficient evidence for causality of the variants. METHODS: Exome or genome sequencing was carried out in 15 families. Clinical and neuroradiological evaluation was performed for all affected individuals, including review of 10 previously reported individuals. The pathogenicity of TARS2 variants was evaluated using in vitro assays, and a zebrafish model. RESULTS: We report 18 new individuals harboring biallelic TARS2 variants. Phenotypically, these individuals show developmental delay/intellectual disability, regression, cerebellar and cerebral atrophy, basal ganglia signal alterations, hypotonia, cerebellar signs and increased blood lactate. In vitro studies showed that variants within the TARS2301-381 region had decreased binding to Rag GTPases, likely impairing mTORC1 activity. The zebrafish model recapitulated key features of the human phenotype and unraveled dysregulation of downstream targets of mTORC1 signaling. Functional testing of the variants confirmed the pathogenicity in a zebrafish model. CONCLUSION: We define the clinico-radiological spectrum of TARS2-related mitochondrial disease, unveil the likely involvement of the mTORC1 signaling pathway as a distinct molecular mechanism, and establish a TARS2 zebrafish model as an important tool to study variant pathogenicity

Morning Glory Disc Anomaly Associated with Ipsilateral Optic Nerve and Chiasm Thickening: Three Cases and Review of the Literature

Several extraorbital findings have been described in morning glory disc anomaly (MGDA), including optic pathway abnormalities. We want to emphasize the importance of looking for ipsilateral optic nerve and chiasm thickening in MGDA-affected patients because we think that it may be a relevant common associated finding to date not stressed by anyone. We report three cases of clinically diagnosed unilateral MGDA in which magnetic resonance imaging revealed enlargement of the ipsilateral optic nerve and chiasm. A literature analysis was made and previously reported MGDA cases, and case series were checked, looking for described, or misunderstood similar magnetic resonance imaging findings. Three other cases with very similar prechiasmatic optic nerve and chiasm findings were identified from the literature. Two further cases are discussed as possibly characterized by similar misinterpreted magnetic resonance features. Our study broadens the constellation of intra- and extraorbital findings of MGDA. Though magnetic resonance imaging is not sufficient to determine the neuropathological substrate of this finding, clinicians and radiologists should be aware of the possible association of MGDA with ipsilateral thickening of the optic nerve and chiasm, to properly plan the clinical and imaging follow-up. © 2017 Georg Thieme Verlag KG Stuttgart.New York

Novel SETX variants in a patient with ataxia, neuropathy, and oculomotor apraxia are associated with normal sensitivity to oxidative DNA damaging agents

Background: Homozygous and compound heterozygous mutations in SETX are associated with AOA2 disease, a recessive form of ataxia with oculomotor apraxia and neuropathy with onset of ataxia between the first and second decade of life. The majority of the AOA2 mutated cell lines tested show hypersensitivity to oxidative DNA damaging agents, with one exception. Results: We describe a patient presenting with early-onset progressive ataxia, oculomotor apraxia, axonal sensory-motor neuropathy, optic atrophy, delayed psychomotor development, and a behavior disorder. The patient carries two novel missense variants in the SETX gene. Based on the hypothesis that the patient's clinical phenotype may represent an atypical form of the AOA2 disease, we tested the patient-derived cell line for hypersensitivity to oxidative DNA damaging agents, with negative results. Conclusions: The lack of hypersensitivity we observed may be explained either by considering the atypical clinical picture of the patient analyzed or, alternatively, by hypothesizing that the variants detected are not the cause of the observed phenotype. Consistent with the first hypothesis of an atypical AOA2 form and based on the multiple functions of senataxin reported so far, it is likely that different sets of SETX mutations. /variants may have variable functional effects that still need to be functionally characterized. The possibility that the severe and complicated clinical picture presented by the patient described here represents a clinical entity differing from the known recessive ataxias should be considered as well

Are Treated Celiac Patients at Risk for Mycotoxins? An Italian Case-Study

Urinary biomarkers of mycotoxin exposure were evaluated in a group of celiac patients (n = 55) and in a control group of healthy subjects (n = 50) following their habitual diet. Deoxynivalenol (DON), zearalenone (ZEN), and fumonisin B1 (FB1) were monitored in 105 urinary samples collected from the two groups. Dietary habits were also recorded through compilation of a seven-day weighed dietary diary. Biomarkers of mycotoxin exposure were detected in 21 celiac patients and in 15 control subjects, corresponding to about 34% of total participants. In particular, ZEN was the most detected mycotoxin among all the studied subjects with a total of 19 positive cases. Results did not show a statistically significant difference in mycotoxin exposure between the two groups, and the presence of specific mycotoxins was not related to the intake of any particular food category. Our findings suggest little urgency of specific regulation for gluten free products, although the prevalence of exposure observed in free-living diets of both celiac and healthy subjects underlines the need of a constant surveillance on mycotoxins occurrence at large

Brain-injured Survivors of Monochorionic Twin Pregnancies Complicated by Single Intrauterine Death: MR Findings in a Multicenter Study

Purpose To describe and classify the range of brain injuries present at prenatal, in-utero magnetic resonance (MR) imaging in co-twin survivors of monochorionic (MC) twin pregnancies complicated by single intrauterine death (SIUD). Materials and Methods This retrospective, observational study from six tertiary fetal medicine centers that perform tertiary-level prenatal in-utero MR studies reviewed cases in which prenatal in-utero MR imaging had shown a brain injury in a surviving co-twin of a twin pregnancy with a MC component complicated by SIUD. Results Forty-two surviving MC twins were described. The primary distinction of brain abnormalities was into nonfocal and focal lesions. The nonfocal lesions included periventricular leukomalacia (group 1; two fetuses), generalized encephalomalacia (group 2; nine fetuses), posterior encephalomalacia (group 3; seven fetuses), and bilateral parasagittal and perisylvian injury (group 4; three fetuses). The focal lesions included nonhemorrhagic lesions (group 5; 14 fetuses) and hemorrhagic lesions (group 6; seven fetuses). Focal brain lesions were more likely to be found in the surviving MC pregnancies complicated by twin-twin transfusion syndrome (TTTS) (odds ratio, 2.4; 95% confidence interval: 1.3, 18.5; P = .01) and in fetuses that underwent an obstetric intervention (odds ratio, 2.8; 95% confidence interval: 1.8, 23.6; P = .006). Conclusion Brain injury of the surviving co-twin after SIUD in MC pregnancies is usually of ischemic origin and spares the brainstem and cerebellum. Focal brain lesions are more frequent in pregnancies complicated by TTTS or in those where an intervention has been performed