دورية أكاديمية
أعرض في EDS

Intellectual disability and autism in propionic acidemia: a biomarker-behavioral investigation implicating dysregulated mitochondrial biology.

التفاصيل البيبلوغرافية
العنوان: Intellectual disability and autism in propionic acidemia: a biomarker-behavioral investigation implicating dysregulated mitochondrial biology.
المؤلفون: Shchelochkov OA; Organic Acid Research Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA., Farmer CA; Neurodevelopmental and Behavioral Phenotyping Service, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, 20892, USA., Chlebowski C; Neurodevelopmental and Behavioral Phenotyping Service, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, 20892, USA., Adedipe D; Neurodevelopmental and Behavioral Phenotyping Service, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, 20892, USA., Ferry S; Organic Acid Research Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA., Manoli I; Organic Acid Research Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA., Pass A; Organic Acid Research Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA., McCoy S; Organic Acid Research Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA., Van Ryzin C; Organic Acid Research Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA., Sloan J; Organic Acid Research Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA., Thurm A; Neurodevelopmental and Behavioral Phenotyping Service, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, 20892, USA., Venditti CP; Organic Acid Research Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA. venditti@mail.nih.gov.
المصدر: Molecular psychiatry [Mol Psychiatry] 2024 Apr; Vol. 29 (4), pp. 974-981. Date of Electronic Publication: 2024 Jan 11.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Specialist Journals Country of Publication: England NLM ID: 9607835 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5578 (Electronic) Linking ISSN: 13594184 NLM ISO Abbreviation: Mol Psychiatry Subsets: MEDLINE
أسماء مطبوعة: Publication: 2000- : Houndmills, Basingstoke, UK : Nature Publishing Group Specialist Journals
Original Publication: Houndmills, Hampshire, UK ; New York, NY : Stockton Press, c1996-
مواضيع طبية MeSH: Propionic Acidemia*/genetics , Biomarkers*/blood , Intellectual Disability*/genetics , Mitochondria*/metabolism , Autism Spectrum Disorder*/metabolism , Autism Spectrum Disorder*/genetics, Humans ; Male ; Female ; Child ; Child, Preschool ; Adolescent ; Autistic Disorder/metabolism ; Autistic Disorder/genetics ; Adult ; Methylmalonyl-CoA Decarboxylase/genetics ; Methylmalonyl-CoA Decarboxylase/metabolism ; Young Adult ; Carnitine/analogs & derivatives ; Carnitine/metabolism ; Carnitine/blood ; Citrates
مستخلص: Propionic acidemia (PA) is an autosomal recessive condition (OMIM #606054), wherein pathogenic variants in PCCA and PCCB impair the activity of propionyl-CoA carboxylase. PA is associated with neurodevelopmental disorders, including intellectual disability (ID) and autism spectrum disorder (ASD); however, the correlates and mechanisms of these outcomes remain unknown. Using data from a subset of participants with PA enrolled in a dedicated natural history study (n = 33), we explored associations between neurodevelopmental phenotypes and laboratory parameters. Twenty (61%) participants received an ID diagnosis, and 12 of the 31 (39%) who were fully evaluated received the diagnosis of ASD. A diagnosis of ID, lower full-scale IQ (sample mean = 65 ± 26), and lower adaptive behavior composite scores (sample mean = 67 ± 23) were associated with several biomarkers. Higher concentrations of plasma propionylcarnitine, plasma total 2-methylcitrate, serum erythropoietin, and mitochondrial biomarkers plasma FGF21 and GDF15 were associated with a more severe ID profile. Reduced 1- 13 C-propionate oxidative capacity and decreased levels of plasma and urinary glutamine were also associated with a more severe ID profile. Only two parameters, increased serum erythropoietin and decreased plasma glutamine, were associated with ASD. Plasma glycine, one of the defining features of PA, was not meaningfully associated with either ID or ASD. Thus, while both ID and ASD were commonly observed in our PA cohort, only ID was robustly associated with metabolic parameters. Our results suggest that disease severity and associated mitochondrial dysfunction may play a role in CNS complications of PA and identify potential biomarkers and candidate surrogate endpoints.
(© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
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معلومات مُعتمدة: ZICMH002961 U.S. Department of Health & Human Services | National Institutes of Health (NIH); ZIE HG200354 United States ImNIH Intramural NIH HHS; ZIA HG200318 United States ImNIH Intramural NIH HHS; 1ZIEHG200354 U.S. Department of Health & Human Services | National Institutes of Health (NIH); 1ZIAHG200318 U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI); ZIC MH002961 United States ImNIH Intramural NIH HHS
المشرفين على المادة: 0 (Biomarkers)
EC 7.2.4.3 (Methylmalonyl-CoA Decarboxylase)
6061-96-7 (2-methylcitric acid)
S7UI8SM58A (Carnitine)
0 (Citrates)
تواريخ الأحداث: Date Created: 20240110 Date Completed: 20240613 Latest Revision: 20240617
رمز التحديث: 20240617
مُعرف محوري في PubMed: PMC11176071
DOI: 10.1038/s41380-023-02385-5
PMID: 38200289
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-5578
DOI:10.1038/s41380-023-02385-5