Inborn Errors of Metabolism Associated With Autism Among Children: A Multicenter Study from Iran

Objective: This study aimed to find the common inborn errors of metabolism in Iranian patients with autism spectrum disorder. Methods: In this cross-sectional multicenter study, 105 children and adolescents with autism spectrum disorder from six centers in different cities of Iran were enrolled between August, 2019 and October, 2020. Metabolic screening, including measuring plasma levels of amino acids, acylcarnitines, creatine, and guanidinoacetate, and urinary levels of organic acids, purines, and pyrimidines was performed. Other data, including age, parental consanguinity, history of seizure, developmental mile-stones, and physical examination, were also recorded. Results: An inborn error of metabolism was found in 13 (12.4%) patients. Five patients (4.8%) had cerebral creatine deficiency syndrome, 4 (3.8%) had arginine succinate aciduria, 2- methylbutyryl glycinuria, short-chain acyl-CoA dehydrogenase deficiency, and combined methylmalonic aciduria/malonic aciduria. There was a strong association between positive metabolic evaluation and parental consanguinity, history of seizures, microcephaly, and delayed development. Conclusions: Our results suggest that metabolic screening should be performed in the cases of autism associated with parental consanguinity, developmental delay, and a history of seizures. The assays to be considered as a screening panel include plasma or blood amino acids, acylcarnitines, creatine and guanidinoacetate, and urinary levels of organic acids.

Integrated Multianalyte Second-Tier Testing for Newborn Screening for MSUD, IVA, and GAMT Deficiencies

Abstract Advances in mass spectrometry have allowed for expansion of newborn screening test panels over the last decade but with increased numbers of disorders have come increased concerns with false-positive rates. The introduction of second-tier testing has improved the specificity of screening for a number of disorders without any corresponding sacrifice in sensitivity. Such testing does, however, put pressure on scarce laboratory resources including instrument and personnel time and even the bloodspot sample itself. The British Columbia Newborn Screening Program has developed an integrated second-tier screening approach to improve test performance without the requirement to resample and reprocess the original bloodspot specimen. By utilizing the residual extract from the first-tier assay and introducing a chromatography step as the second tier, we have been able to reduce false-positive rates due to interfering isobaric compounds for 3 different disorders (maple syrup urine disease, isovaleric aciduria, and guanidinoacetate methyltransferase) in a single multianalyte assay.