Abnormal concentrations of acetylated amino acids in cerebrospinal fluid in <scp>acetyl‐CoA</scp> transporter deficiency

Šikić, Katarina; Peters, Tobias; Marušić, Eugenija; Čagalj, Ivana; Ramadža, Danijela Petković; Žigman, Tamara; Fumić, Ksenija; Fernández, Esperanza; Gevaert, Kris; Debeljak, Željko; Wevers, Ron A.; Barić, Ivo

doi:10.1002/jimd.12549

Cited by 4 publications

(1 citation statement)

References 44 publications

(93 reference statements)

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“…While brain tissue is not easily accessible, the surrounding cerebrospinal fluid (CSF) is often used as a go-to sample for metabolic studies, which have provided insights in the pathophysiology of Parkinson’s and Alzheimer’s disease, 1 – 3 multiple sclerosis, 4 tuberculous meningitis, 5 , 6 and inborn errors of metabolism. 7 – 9 Changes in CSF metabolites are attributed to changes in brain metabolism, but their source and transport need to be accounted for. Brain-derived metabolites include intermediate or end products of metabolic processes that occur in the cells of the CNS.…”

Section: Introductionmentioning

confidence: 99%

Metabolite transport across central nervous system barriers

Carstens,

Verbeek,

Rohlwink

et al. 2024

J Cereb Blood Flow Metab

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Metabolomic analysis of cerebrospinal fluid (CSF) is used to improve diagnostics and pathophysiological understanding of neurological diseases. Alterations in CSF metabolite levels can partly be attributed to changes in brain metabolism, but relevant transport processes influencing CSF metabolite concentrations should be considered. The entry of molecules including metabolites into the central nervous system (CNS), is tightly controlled by the blood-brain, blood-CSF, and blood-spinal cord barriers, where aquaporins and membrane-bound carrier proteins regulate influx and efflux via passive and active transport processes. This report therefore provides reference for future CSF metabolomic work, by providing a detailed summary of the current knowledge on the location and function of the involved transporters and routing of metabolites from blood to CSF and from CSF to blood.

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Section: Introductionmentioning

confidence: 99%

Metabolite transport across central nervous system barriers

Carstens,

Verbeek,

Rohlwink

et al. 2024

J Cereb Blood Flow Metab

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Huppke–Brendel syndrome: Novel cases and a therapeutic trial with ketogenic diet and N‐acetylcysteine

Šikić,

Peters,

Engelke

et al. 2024

JIMD Reports

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Huppke–Brendel syndrome (HBS) is an autosomal recessive disorder caused by SLC33A1 mutations, a gene coding for the acetyl‐CoA transporter‐1 (AT‐1). So far it has been described in nine pediatric and one adult patient. Therapeutic trials with copper histidinate failed to achieve any clinical improvement. Here, we describe the clinical characteristics of two novel patients, one of them diagnosed by gene analysis and his sib postmortally based on clinical characteristics. We demonstrate a therapeutic trial with acetylation therapy, consisting of N‐acetylcysteine and ketogenic diet, in one of them. We provide biochemical data on N‐acetylated amino acids in cerebrospinal fluid (CSF) and plasma before and after starting this treatment regimen. Our results indicate that ketogenic diet and N‐acetylcysteine do not seem to normalize the concentrations of N‐acetylated amino acids in CSF or plasma. The overall metabolic pattern shows a trend toward lowered levels of N‐acetylated amino acids in CSF and to a lesser extent in plasma. Although there are some assumptions, the function of AT‐1 is still not clear and further studies are needed to better understand mechanisms underlying this complex disorder.

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