Clinical and Behavioral Correlates of Blood Acylcarnitine Profiles in Children with Autism Spectrum Disorder: A Cross-Sectional Analysis
<b>Background/Objectives</b>: Autism Spectrum Disorder (ASD) etiology is complex, involving genetics and environmental factors, and associated with impaired energy metabolism. Mitochondrial fatty acid oxidation (mFAO) is instrumental to energy production through the oxidation of acylcarn...
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2025-06-01
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| author | Adriana Prato Martina Randazzo Maria Anna Messina Giovanni Puglisi Laura Rosy Aleo Fiorella Ciantia Lara Cirnigliaro Renata Rizzo Rita Barone |
| author_facet | Adriana Prato Martina Randazzo Maria Anna Messina Giovanni Puglisi Laura Rosy Aleo Fiorella Ciantia Lara Cirnigliaro Renata Rizzo Rita Barone |
| author_sort | Adriana Prato |
| collection | DOAJ |
| description | <b>Background/Objectives</b>: Autism Spectrum Disorder (ASD) etiology is complex, involving genetics and environmental factors, and associated with impaired energy metabolism. Mitochondrial fatty acid oxidation (mFAO) is instrumental to energy production through the oxidation of acylcarnitines (ACs). We performed a comprehensive investigation of blood AC profiles in a pediatric ASD cohort, aiming to define ASD subgroups based on AC profiles and link these profiles to key clinical features and comorbidities using a phenotype-first approach. <b>Methods</b>: Blood levels of 31 ACs (μmol/L) collected from 102 ASD patients and 117 healthy controls (HCs) were evaluated via tandem mass spectrometry. The percentile distribution of blood AC levels in HC samples was computed to define the normal reference range (RR) and identify values corresponding to the 10th and 90th percentiles. Cognitive levels, emotional–behavioral disturbances and the severity of ASD symptoms (Autism Diagnostic Observation Schedule-Calibrated Severity Score ADOS-CSS) were assessed. Clinical correlates of ASD groups based on AC profiles were evaluated. <b>Results</b>: Three ASD subgroups were identified based on the percentile distribution of AC levels: group A (ACs < 10th percentile), group B (ACs 10th–90th percentile) and group C (ACs > 90th percentile) (abnormal AC number ≥ 3). Out of the thirty-one analyzed ACs in DBSs, fifteen (48.4%) were significantly different when comparing ASD group A to ASD group C. There was a significant difference in the severity of autism symptoms (ADOS CSS) related to the repetitive and restricted behaviors domain (CSS RRB) among the different groups (χ<sup>2</sup>(2) = 6.26; <i>p</i> = 0.044). The post hoc Dunn’s test with Bonferroni correction showed that ADOS-CSS RRB was significantly higher in ASD group A compared to ASD group B (<i>p</i> = 0.013). AC C14 was more frequently decreased (<10th pc) in patients with more severe symptoms (<i>p</i> = 0.006); C10:1 tended to be more frequently increased (>90th pc) in patients with lower clinical severity (<i>p</i> = 0.052). <b>Conclusions</b>: This study highlights differences across blood AC levels in children with ASD and conveys novel information on clinical severity in ASD patients with abnormal blood AC profiles. Thus, examining metabolic profiles may provide helpful insights to understand the variability of ASD symptoms. |
| format | Article |
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| publishDate | 2025-06-01 |
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| spelling | doaj-art-0ece0a1ab3f74a3fbc8d7f8fa0f11e092025-07-25T13:18:15ZengMDPI AGChildren2227-90672025-06-0112784810.3390/children12070848Clinical and Behavioral Correlates of Blood Acylcarnitine Profiles in Children with Autism Spectrum Disorder: A Cross-Sectional AnalysisAdriana Prato0Martina Randazzo1Maria Anna Messina2Giovanni Puglisi3Laura Rosy Aleo4Fiorella Ciantia5Lara Cirnigliaro6Renata Rizzo7Rita Barone8Child and Adolescent Neurology and Psychiatric Section, Department of Clinical and Experimental Medicine, Catania University, 95123 Catania, ItalyChild and Adolescent Neurology and Psychiatric Section, Department of Clinical and Experimental Medicine, Catania University, 95123 Catania, ItalyExpanded Newborn Screening Laboratory, A.O.U Policlinico “G. Rodolico—San Marco”, 95123 Catania, ItalyChild and Adolescent Neurology and Psychiatric Section, Department of Clinical and Experimental Medicine, Catania University, 95123 Catania, ItalyChild and Adolescent Neurology and Psychiatric Section, Department of Clinical and Experimental Medicine, Catania University, 95123 Catania, ItalyChild and Adolescent Neurology and Psychiatric Section, Department of Clinical and Experimental Medicine, Catania University, 95123 Catania, ItalyChild and Adolescent Neurology and Psychiatric Section, Department of Clinical and Experimental Medicine, Catania University, 95123 Catania, ItalyChild and Adolescent Neurology and Psychiatric Section, Department of Clinical and Experimental Medicine, Catania University, 95123 Catania, ItalyChild and Adolescent Neurology and Psychiatric Section, Department of Clinical and Experimental Medicine, Catania University, 95123 Catania, Italy<b>Background/Objectives</b>: Autism Spectrum Disorder (ASD) etiology is complex, involving genetics and environmental factors, and associated with impaired energy metabolism. Mitochondrial fatty acid oxidation (mFAO) is instrumental to energy production through the oxidation of acylcarnitines (ACs). We performed a comprehensive investigation of blood AC profiles in a pediatric ASD cohort, aiming to define ASD subgroups based on AC profiles and link these profiles to key clinical features and comorbidities using a phenotype-first approach. <b>Methods</b>: Blood levels of 31 ACs (μmol/L) collected from 102 ASD patients and 117 healthy controls (HCs) were evaluated via tandem mass spectrometry. The percentile distribution of blood AC levels in HC samples was computed to define the normal reference range (RR) and identify values corresponding to the 10th and 90th percentiles. Cognitive levels, emotional–behavioral disturbances and the severity of ASD symptoms (Autism Diagnostic Observation Schedule-Calibrated Severity Score ADOS-CSS) were assessed. Clinical correlates of ASD groups based on AC profiles were evaluated. <b>Results</b>: Three ASD subgroups were identified based on the percentile distribution of AC levels: group A (ACs < 10th percentile), group B (ACs 10th–90th percentile) and group C (ACs > 90th percentile) (abnormal AC number ≥ 3). Out of the thirty-one analyzed ACs in DBSs, fifteen (48.4%) were significantly different when comparing ASD group A to ASD group C. There was a significant difference in the severity of autism symptoms (ADOS CSS) related to the repetitive and restricted behaviors domain (CSS RRB) among the different groups (χ<sup>2</sup>(2) = 6.26; <i>p</i> = 0.044). The post hoc Dunn’s test with Bonferroni correction showed that ADOS-CSS RRB was significantly higher in ASD group A compared to ASD group B (<i>p</i> = 0.013). AC C14 was more frequently decreased (<10th pc) in patients with more severe symptoms (<i>p</i> = 0.006); C10:1 tended to be more frequently increased (>90th pc) in patients with lower clinical severity (<i>p</i> = 0.052). <b>Conclusions</b>: This study highlights differences across blood AC levels in children with ASD and conveys novel information on clinical severity in ASD patients with abnormal blood AC profiles. Thus, examining metabolic profiles may provide helpful insights to understand the variability of ASD symptoms.https://www.mdpi.com/2227-9067/12/7/848autism spectrum disorderADOSdried blood spotsESI-MS/MSfatty acid oxidationmetabolism |
| spellingShingle | Adriana Prato Martina Randazzo Maria Anna Messina Giovanni Puglisi Laura Rosy Aleo Fiorella Ciantia Lara Cirnigliaro Renata Rizzo Rita Barone Clinical and Behavioral Correlates of Blood Acylcarnitine Profiles in Children with Autism Spectrum Disorder: A Cross-Sectional Analysis Children autism spectrum disorder ADOS dried blood spots ESI-MS/MS fatty acid oxidation metabolism |
| title | Clinical and Behavioral Correlates of Blood Acylcarnitine Profiles in Children with Autism Spectrum Disorder: A Cross-Sectional Analysis |
| title_full | Clinical and Behavioral Correlates of Blood Acylcarnitine Profiles in Children with Autism Spectrum Disorder: A Cross-Sectional Analysis |
| title_fullStr | Clinical and Behavioral Correlates of Blood Acylcarnitine Profiles in Children with Autism Spectrum Disorder: A Cross-Sectional Analysis |
| title_full_unstemmed | Clinical and Behavioral Correlates of Blood Acylcarnitine Profiles in Children with Autism Spectrum Disorder: A Cross-Sectional Analysis |
| title_short | Clinical and Behavioral Correlates of Blood Acylcarnitine Profiles in Children with Autism Spectrum Disorder: A Cross-Sectional Analysis |
| title_sort | clinical and behavioral correlates of blood acylcarnitine profiles in children with autism spectrum disorder a cross sectional analysis |
| topic | autism spectrum disorder ADOS dried blood spots ESI-MS/MS fatty acid oxidation metabolism |
| url | https://www.mdpi.com/2227-9067/12/7/848 |
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