Inborn Errors of Metabolism Associated With Autism Spectrum Disorders: Approaches to Intervention

Žigman, Tamara; Ramadža, Danijela Petković; Šimić, Goran; Barić, Ivo

doi:10.3389/fnins.2021.673600

Cited by 39 publications

(30 citation statements)

References 84 publications

(95 reference statements)

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“…However, it has previously been explained in terms of mitochondrial dysfunction. In ASD patients, mitochondrial dysfunction is a common metabolic disorder ( 5 ). In their study, Rossignol et al ( 26 ) argue that mitochondrial dysfunction can result in the loss of cellular integrity in specific organs, including muscle and liver, enabling the release of CK into the bloodstream, leading to increased serum levels of CK.…”

Section: Discussionmentioning

confidence: 99%

“…It was reported that in 2013, the prevalence of ASD was 0.7% in China ( 4 ). While ASD's pathogenesis is still unknown, recent studies have found that some ASDs may be associated with inborn errors of metabolism ( 5 ). Some metabolic disorders can only be identified by non-targeted biochemical markers ( 5 ) and serumcreatine kinase (CK) values may be one of the potential indicators to it ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

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Case report: One child with an autism spectrum disorder who had chronically elevated serum levels of CK and CK-MB

Rong

Zhao²,

Fu³

et al. 2022

Front. Psychiatry

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Some patients with autism spectrum disorder (ASD) exhibit elevated serum creatine kinase levels, which are believed to be associated with mitochondrial dysfunction. Although a few articles have reported this situation in the past and the increase mostly ranges from 100 to 300 U/L, there is a paucity of previous study focusing on the serum creatine kinase MB isoenzyme. This article discusses a 5-year-old girl with ASD, whose serum creatine kinase and creatine kinase MB isoenzyme have been rising for nearly 2 years, fluctuating at 584–993 and 111–625 U/L respectively. Except for behavioral and language symptoms associated with ASD, the child appears normal in other aspects. The child's laboratory tests showed no abnormality, except that the serum levels of lactic acid was slightly higher than normal (1.89 mmol/L, normal 1.33–1.78 mmol/L). The child was prescribed with a traditional Chinese medicine during the process and the serum creatine kinase MB isoenzyme level decreased dramatically to 111 U/L after the treatment. This study firstly recorded the serum creatine kinase levels and the MB isoenzyme in patients with autism spectrum disorder for nearly 2 years, indicating that patients with ASD may experience long-term increases in serum creatine kinase and creatine kinase MB isoenzyme, and that the traditional Chinese medicine decoction Xinfukang can temporarily reduce the serum creatine kinase MB isoenzyme level in patients. Nevertheless, the effect is not sustained. Therefore, it is of great importance to conduct long-term longitudinal studies so as to elucidate the potential mechanism responsible for long-term elevation of serum creatine kinase level.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Case report: One child with an autism spectrum disorder who had chronically elevated serum levels of CK and CK-MB

Rong

Zhao²,

Fu³

et al. 2022

Front. Psychiatry

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“…Interestingly, such alterations can be rescued by the oral administration of the dipeptide glycyl-tryptophan (Gly-Trp) [ 27 ], a tryptophan precursor whose absorption does not require the intestinal expression of ACE2. Additionally, human subjects bearing an SLC6A19 loss-of-function mutation develop a disorder called Hartnup disease, characterized notably by the co-occurrence of neuropsychiatric symptoms and low blood levels of neutral amino acids [ 62 , 63 ]. In addition to SLC6A19 , we also found that in SARS-CoV2-infected enterocytes, ACE2 co-regulates with several crucial genes of the dopamine/trace amines synthetic pathways.…”

Section: Discussionmentioning

confidence: 99%

Molecular Insights into SARS-CoV2-Induced Alterations of the Gut/Brain Axis

Nataf

Pays

2021

IJMS

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For a yet unknown reason, a substantial share of patients suffering from COVID-19 develop long-lasting neuropsychiatric symptoms ranging from cognitive deficits to mood disorders and/or an extreme fatigue. We previously reported that in non-neural cells, angiotensin-1 converting enzyme 2 (ACE2), the gene coding for the SARS-CoV2 host receptor, harbors tight co-expression links with dopa-decarboxylase (DDC), an enzyme involved in the metabolism of dopamine. Here, we mined and integrated data from distinct human expression atlases and found that, among a wide range of tissues and cells, enterocytes of the small intestine express the highest expression levels of ACE2, DDC and several key genes supporting the metabolism of neurotransmitters. Based on these results, we performed co-expression analyses on a recently published set of RNA-seq data obtained from SARS-CoV2-infected human intestinal organoids. We observed that in SARS-CoV2-infected enterocytes, ACE2 co-regulates not only with DDC but also with a specific group of genes involved in (i) the dopamine/trace amines metabolic pathway, (ii) the absorption of microbiota-derived L-DOPA and (iii) the absorption of neutral amino acids serving as precursors to neurotransmitters. We conclude that in patients with long COVID, a chronic infection and inflammation of small intestine enterocytes might be indirectly responsible for prolonged brain alterations.

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“…The variant has been reported in a Saudi Arabian family, in which two affected patients with homocystinuria were homozygous for the variant inherited from unaffected heterozygous parents [157]. There are reports that children with classical homocystinuria may have isolated ASD due to cystathionine-β-synthase deficiency [158,159].…”

Section: Pancreas and Livermentioning

confidence: 99%

Integrative Functional Genomic Analysis in Multiplex Autism Families from Kazakhstan

Perfilyeva¹,

Bespalova

Perfilyeva

et al. 2022

Disease Markers

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The study of extended pedigrees containing autism spectrum disorder- (ASD-) related broader autism phenotypes (BAP) offers a promising approach to the search for ASD candidate variants. Here, a total of 650,000 genetic markers were tested in four Kazakhstani multiplex families with ASD and BAP to obtain data on de novo mutations (DNMs), common, and rare inherited variants that may contribute to the genetic risk for developing autistic traits. The variants were analyzed in the context of gene networks and pathways. Several previously well-described enriched pathways were identified, including ion channel activity, regulation of synaptic function, and membrane depolarization. Perhaps these pathways are crucial not only for the development of ASD but also for ВАР. The results also point to several additional biological pathways (circadian entrainment, NCAM and BTN family interactions, and interaction between L1 and Ankyrins) and hub genes (CFTR, NOD2, PPP2R2B, and TTR). The obtained results suggest that further exploration of PPI networks combining ASD and BAP risk genes can be used to identify novel or overlooked ASD molecular mechanisms.

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Inborn Errors of Metabolism Associated With Autism Spectrum Disorders: Approaches to Intervention

Cited by 39 publications

References 84 publications

Case report: One child with an autism spectrum disorder who had chronically elevated serum levels of CK and CK-MB

Case report: One child with an autism spectrum disorder who had chronically elevated serum levels of CK and CK-MB

Molecular Insights into SARS-CoV2-Induced Alterations of the Gut/Brain Axis

Integrative Functional Genomic Analysis in Multiplex Autism Families from Kazakhstan

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