RESUMO
Background and aims: The occurrence of thiamine metabolism dysfunction syndrome (THMD), a rare autosomal recessive condition, may be linked to various mutations found in the TPK1 and SLC19A3 genes. The disease chiefly manifests through ataxia, muscle hypotonia, abrupt or subacute onset encephalopathy, and a decline in developmental milestones achieved during the early stages of infancy. We present findings from an investigation that involved two individuals from Iran, both of whom experienced seizures along with ataxia and hypotonia. The underlying genetic causes were found with the use of next-generation sequencing (NGS) technology, which has facilitated the detection of causal changes in a variety of genetic disorders. Material and methods: The selection of cases for this study was based on the phenotypic and genetic information that was obtainable from the Center for Comprehensive Genetic Services. The genetic basis for the problems observed among the participants was determined through the application of whole-exome sequencing (WES). Subsequently, sanger sequencing was employed as a means of validating any identified variations suspected to be causative. Results: The first patient exhibited a homozygous mutation in the TPK1 gene, NM_022445.4:c.224 T > A:p.I75 N, resulting in the substitution of isoleucine for asparagine at position 75 (p.I75 N). In our investigation, patient 2 exhibited a homozygous variant, NM_025243.4:c.1385dupA:pY462X, within the SLC19A3 gene. Conclusions: Collectively, when presented with patients showcasing ataxia, encephalopathy, and basal ganglia necrosis, it is essential to account for thiamine deficiency in light of the potential advantages of prompt intervention. At times, it may be feasible to rectify this deficiency through the timely administration of thiamine dosages. Accordingly, based on the results of the current investigation, these variations may be useful for the diagnosis and management of patients with THMD.
RESUMO
Several epidemiologic studies have evaluated the relation between serum/plasma brain-derived neurotrophic factor (BDNF) levels and glycemic parameters, but the findings were conflicting. We performed a systematic review and meta-analysis to compare circulating BDNF levels in individuals with type 2 diabetes (T2D) or other glycemic disorders with healthy controls and to evaluate correlation between BDNF concentrations with glycemic profile. A systematic search up to July 2020 was conducted in reliable electronic databases (MEDLINE (Pubmed), EMBASE, Scopus) and Google scholar. Sixteen observational studies compared serum/plasma BDNF levels in diabetic patients (or individuals with glycemic disorders) vs. healthy controls or reported correlations between serum BDNF levels and glycemic parameters in adults were included in the review. Overall weighted mean difference (WMD) of circulating BDNF levels in 1306 patients with T2D (or other glycemic disorders) was 1.12 ng/mL lower than 1250 healthy subjects (WMD: - 1.12; 95%CI - 1.37, - 0.88, I2 = 98.7%, P < 0.001). Subgroup analysis revealed that both diabetic patients and subjects with other glycemic disorders had lower serum/plasma BDNF levels than healthy controls (WMD: - 1.74; 95%CI - 2.15, - 1.33 and WMD: - 0.49; 95%CI - 0.82, - 0.16, respectively). No significant correlation was found between BDNF levels and glycemic parameters [fasting blood glucose (FBG) (Fisher's Z = 0.05; 95%CI - 0.21, 0.11; n = 1400), homeostatic model assessment for insulin resistance (HOMA-IR) (Fisher's Z = 0.12; 95%CI - 0.20, 0.44; n = 732) and glycosylated hemoglobin (HbA1c) (Fisher's Z = 0.04; 95%CI - 0.05, 0.12; n = 2222)]. We found that diabetic patients and subjects with glycemic disorders had lower circulating BDNF levels than healthy controls. However, there was no significant correlation between BDNF concentrations and glycemic parameters including FBG, HOMA-IR and HbA1c. Further prospective investigations are required to confirm these findings.