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Background: Small for gestational age (SGA) and large for gestational age (LGA) newborns are at increased risk for developmental, metabolic and cardiovascular morbidities., Aims: To compare the metabolic biomarkers of SGA and LGA infants with those of appropriate for gestational age (AGA) newborns in order to shed more light on a possible pathogenesis of those morbidities., Study Design: An observational retrospective study., Subjects: 70,809 term newborns divided into AGA, SGA, LGA, and severe subcategories (<3rd percentile or ≥97th percentile)., Outcome Measures: 18 metabolites were measured by dried blood tandem mass spectrometry and compared in between groups in univariate and multivariate logistic regression., Results: SGA newborns had a significant likelihood for elevated methionine, proline, free carnitine, and reduced valine levels compared to AGA newborns (P < .0001). Severe SGA showed more apparent trends including elevated leucine. LGA newborns had a significant likelihood for low citrulline, glutamine, proline, tyrosine, and elevated leucine levels (P ≤ .0033). Severe LGA newborns showed the same trends, with the exception of citrulline and glutamine., Conclusions: SGA and LGA newborns demonstrate distinct metabolic biomarkers in newborn screening. Most of the altered metabolites in the SGA group were elevated while those in the LGA group were decreased in comparison to AGA newborns. These trends were more apparent in the severe SGA subgroup while they mostly remained the same in the severe LGA subgroup. Whether these metabolic changes are involved with or can predict long-term outcome awaits further trials., (Copyright © 2021. Published by Elsevier B.V.)

Background: Maple syrup urine disease is a rare autosomal-recessive aminoacidopathy, caused by deficient branched-chain 2-keto acid dehydrogenase (BCKD), with subsequent accumulation of branched-chain amino acids (BCAAs): leucine, isoleucine and valine. While most cases of MSUD are classic, some 20% of cases are non-classic variants, designated as intermediate- or intermittent-types. Patients with the latter form usually develop normally and are cognitively intact, with normal BCAA levels when asymptomatic. However, intercurrent febrile illness and catabolism may cause metabolic derailment with life-threatening neurological sequelae. Thus, early detection and dietary intervention are warranted in intermittent MSUD., Patients and Methods: We describe eight patients from four unrelated families, diagnosed with intermittent MSUD. Their presenting symptoms during metabolic crises varied from confusion and decreased consciousness, to ataxia, and acute psychosis. Molecular confirmation of MSUD was pursued via sequencing of the BCKDHA, BCKDHB and DBT genes., Results: All affected individuals were found to harbor bi-allelic pathogenic variants in either BCKDHB or DBT. Of the seven variants, four variants in BCKDHB (p.G101D, p. V103A, p. A221D, p. Y195C) and one variant in DBT (p.K427E) were not previously described., Conclusions: While newborn screening programs allow for early detection of classic MSUD, cases of the intermittent form might go undetected, and present later in childhood following metabolic derailment, with an array of non-specific symptoms. Our experience with the families reported herein adds to the current knowledge regarding the phenotype and mutational spectrum of this unique inborn error of branched-chain amino acid metabolism, and underscore the high index of suspicion required for its diagnosis., Competing Interests: Declaration of competing interest All authors state that they have no competing interests to declare., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)