These authors contributed equally.
Centre for Global Health Research, The Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh Scotland, UK.
J Glob Health. 2018 Dec;8(2):021102. doi: 10.7189/jogh.08.021102.
Inborn errors of metabolism (IEM) are a group of over 500 heterogeneous disorders resulting from a defect in functioning of an intermediate metabolic pathway. Individually rare, their cumulative incidence is thought to be high, but it has not yet been estimated globally. Although outcomes can often be good if recognised early, IEM carry a high fatality rate if not diagnosed. As a result, IEM may contribute significantly to the burden of non-communicable childhood morbidity.
We conducted a systematic literature review of birth prevalence and case fatality of IEM globally, with search dates set from 1980 to 2017. Using random-effects meta-analysis, we estimated birth prevalence of separate classes of IEM and all-cause IEM, split by geographical region. We also estimated levels of parental consanguinity in IEM cases and global case fatality rates and resultant child deaths from all-cause IEM.
49 studies met our selection criteria. We estimate the global birth prevalence of all-cause IEM to be 50.9 per 100 000 live births (95% confidence intervals (CI) = 43.4-58.4). Regional pooled birth prevalence rates showed the highest rates of IEM to be in the Eastern Mediterranean region (75.7 per 100 000 live births, 95% CI = 50.0-101.4), correlating with a higher observed rate of parental consanguinity in studies from this area. We estimate case fatality rates to be 33% or higher in low- and middle-income countries (LMICs), resulting in a minimum of 23 529 deaths from IEM per year globally (95% CI = 20 382-27 427), accounting for 0.4% of all child deaths worldwide.
IEM represent a significant cause of global child morbidity and mortality, comprising a notable proportion of child deaths currently not delineated in global modelling efforts. Our data highlight the need for policy focus on enhanced laboratory capacity for screening and diagnosis, community interventions to tackle parental consanguinity, and increased awareness and knowledge regarding management of IEM, particularly in LMICs.
先天性代谢缺陷（IEM）是一组由中间代谢途径功能缺陷引起的超过 500 种异质性疾病。虽然每个疾病都很少见，但如果能早期发现，其总体发病率可能很高，但目前尚未在全球范围内进行估计。由于如果不进行诊断，IEM 可能导致很高的死亡率，因此如果能早期发现，其治疗效果通常很好。因此，IEM 可能会对儿童非传染性疾病发病率造成严重影响。
我们对全球 IEM 的发病情况和死亡率进行了系统的文献回顾，检索日期设定为 1980 年至 2017 年。使用随机效应荟萃分析，我们按地理位置划分，分别估计了不同类型的 IEM 和所有 IEM 的发病情况。我们还估计了 IEM 病例中父母近亲结婚的比例以及全球 IEM 的死亡率和由此导致的所有病因导致的儿童死亡人数。
49 项研究符合我们的选择标准。我们估计所有病因 IEM 的全球发病情况为每 100000 例活产儿 50.9 例（95%置信区间[CI] = 43.4-58.4）。区域性汇总发病情况显示，发病率最高的地区是东地中海地区（每 100000 例活产儿 75.7 例，95%CI = 50.0-101.4），这与该地区研究中观察到的父母近亲结婚率较高有关。我们估计死亡率在中低收入国家（LMICs）中为 33%或更高，这导致全球每年至少有 23529 例 IEM 死亡（95%CI = 20382-27427），占全球所有儿童死亡人数的 0.4%。
IEM 是全球儿童发病率和死亡率的一个重要原因，在全球建模工作中目前没有明确界定的儿童死亡人数中占了相当大的比例。我们的数据强调需要政策重点关注加强筛查和诊断的实验室能力、针对父母近亲结婚的社区干预措施，以及提高对 IEM 管理的认识和知识，特别是在 LMICs 中。
