Global birth prevalence and mortality from inborn errors of metabolism: a systematic analysis of the evidence

Abstract

BackgroundInborn 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.MethodsWe 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.Findings49 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.ConclusionsIEM 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.

Outcomes in pediatric studies of medium-chain acyl-coA dehydrogenase (MCAD) deficiency and phenylketonuria (PKU): a review

“…Keywords: PKU, MCAD deficiency, Core outcome sets, Rare diseases, Patient-oriented outcomes Background Inherited metabolic diseases (IMD) are a large group of single-gene diseases that are individually rare but when aggregated have an estimated global birth prevalence of 50.9 in 100,000 live births [1]. These diseases are typically diagnosed early in life, often involve complex and resource-intensive medical care [2], and are frequently associated with intense home management and caregiving needs [3].…”

“…For the outcome, cognition and intelligence/IQ, there were 39 different instruments reported among 82 articles, with the Wechsler Intelligence Scales family of measurement instruments [23] being the most frequently specified (33/82 articles, 40%). Executive functioning was measured using 25 different instruments across 32 articles with the Behaviour Rating Inventory of General health biomarkers 2 (4%) 0 (0%) 0 (0%) 2 (7%) [1][2][3][4][5][6][7][8][9][10] indicates top ten most reported or discussed unique outcomes, ties indicated with an asterisks Child psychosocial well-being and self-concept 15 (4%) 0 (0%) 0 (0%) 10 (8%) 5 (7%)…”

The diagnosis of inborn errors of metabolism by an integrative “multi‐omics” approach: A perspective encompassing genomics, transcriptomics, and proteomics

“…Inborn errors of metabolism (IEM) are a heterogeneous group of more than 1000 diseases . Though individually rare, they have a significant cumulatively burden, with a global birth prevalence of 50 per 100 000 . IEM manifest with phenotypes ranging from nonspecific delay in attaining developmental milestones, to acute decompensation with severe metabolic acidosis and sudden premature death.…”

Use of complementary and alternative medicine in patients with inborn errors of metabolism: A single‐center study

“…[6][7][8] There remains a paucity of information on the use and effectiveness of CAM in patients with inborn errors of metabolism (IEM), a group of over 500 disorders that affects approximately 50.9 in 100 000 live births globally. 9 Since IEM are individually rare, conventional treatments are limited for many disorders; therefore, many patients with IEM may use CAM to treat symptoms and improve their quality of life. Recent CAM use estimates include 41% of patients with IEM in Turkey, 10 and nearly half of patients with lysosomal storage diseases in the United States.…”