■关于硫胺素状态的生物标志物之间的关系的信息有限(全血硫胺素二磷酸[ThDP],红细胞转酮酶活性系数[ETKac],和人乳硫胺素[MTh])和硫胺素缺乏的临床表现。
■本研究旨在探讨这些生物标志物与硫胺素反应性疾病(TRD)之间的相关性,基于对硫胺素的良好临床反应的诊断。
■住院婴幼儿(21天至<18个月)呼吸,心脏,和/或提示硫胺素缺乏的神经系统症状与其他治疗一起使用肠胃外硫胺素(每天100mg)治疗≥3d,并进行系统检查。临床病例报告由3名儿科医生审查,确定TRD或非TRD状态的人。社区比较组中的儿童按年龄进行匹配,性别,和居住。用高效液相色谱荧光检测法测定静脉全血ThDP和MTh,用紫外分光光度法测定洗涤红细胞中的ETKac。使用Spearman相关性评估生物标志物之间的关联,使用受试者工作特征曲线框架下的面积来探索预测TRD和ETKac>1.25的生物标志物截止值。
■287名住院儿童和228名社区儿童(平均年龄4.7个月;男性占59.4%)获得了硫胺素生物标志物。ThDP和ETKac的中位数(四分位数范围[IQR])分别为66.9nmol/L(IQR:41.4,96.9nmol/L)和1.25nmol/L(IQR:1.11,1.48nmol/L),分别,在住院儿童中,在228名社区儿童中,分别为64.1nmol/L(IQR:50.0,85.3nmol/L)和1.22nmol/L(IQR:1.12,1.37nmol/L)(两者均P>0.05)。<6个月的母乳喂养母亲中,有45%的MTh<90μg/L。ThDP和ETKAC,但不是MTh,152名TRD儿童和122名无TRD儿童之间存在显着差异,但是重叠的分布破坏了个体对硫胺素反应的预测。
■尽管ETKac,ThDP,和MTh是人群硫胺素状态的有用生物标志物,没有一种生物标志物能够可靠地识别出患有TRD的个别儿童.ThDP对于群体评估更实用,因为不需要制备洗涤的红细胞。该试验在clinicaltrials.gov注册为NCT03626337。
UNASSIGNED: There is limited information on relationships among biomarkers of thiamine status (whole blood thiamine diphosphate [ThDP], erythrocyte transketolase activity coefficient [ETKac], and human milk thiamine [MTh]) and clinical manifestations of thiamine deficiency.
UNASSIGNED: This study aimed to explore correlations among these biomarkers and thiamine responsive disorders (TRDs), a diagnosis based on favorable clinical response to thiamine.
UNASSIGNED: Hospitalized infants and young children (aged 21 d to <18 mo) with respiratory, cardiac, and/or neurological symptoms suggestive of thiamine deficiency were treated with parenteral thiamine (100 mg daily) for ≥3 d alongside other treatments and re-examined systematically. Clinical case reports were reviewed by 3 pediatricians, who determined TRD or non-TRD status. Children in a community comparison group were matched by age, sex, and residence. Venous whole blood ThDP and MTh were determined by high-performance liquid chromatography fluorescence detection and ETKac in washed erythrocytes by ultraviolet spectrophotometry. Associations between biomarkers were assessed using Spearman correlations, and biomarker cutoffs predictive of TRD and ETKac >1.25 were explored using area under the receiver operating characteristic curve framework.
UNASSIGNED: Thiamine biomarkers were available for 287 hospitalized children and 228 community children (mean age 4.7 mo; 59.4% male). Median (interquartile range [IQR]) ThDP and ETKac were 66.9 nmol/L (IQR: 41.4, 96.9 nmol/L) and 1.25 nmol/L (IQR: 1.11, 1.48 nmol/L), respectively, among hospitalized children, and 64.1 nmol/L (IQR: 50.0, 85.3 nmol/L) and 1.22 nmol/L (IQR: 1.12, 1.37 nmol/L) among 228 community children (P > 0.05 for both). Forty-five percent of breastfeeding mothers of infants <6 mo had MTh <90 μg/L. ThDP and ETKac, but not MTh, were significantly different between 152 children with TRD and 122 without TRD, but overlapping distributions undermined prediction of individual responses to thiamine.
UNASSIGNED: Although ETKac, ThDP, and MTh are useful biomarkers of population thiamine status, none of the biomarkers reliably identified individual children with TRD. ThDP is more practical for population assessment because preparing washed erythrocytes is not required.This trial was registered at clinicaltrials.gov as NCT03626337.