Abstract
Pathogenic variants in ALS2 have been detected mostly in juvenile cases of amyotrophic lateral sclerosis (ALS), affecting mainly children and teenagers. Patients with ALS2 mutations demonstrate early onset cortical involvement in ALS. Currently, there are no effective treatment options. There is an immense need to reveal the underlying causes of the disease and to identify potential biomarkers. To shed light onto the metabolomic events that are perturbed with respect to ALS2 mutations, we investigated the metabolites present in the serum and plasma of a three-year-old female patient (AO) harboring pathogenic variants in ALS2, together with her relatives, healthy male and female controls, as well as another two-year-old patient DH, who had mutations at different locations and domains of ALS2. Serum and plasma samples were analyzed with a quantitative metabolomic approach to reveal the identity of metabolites present in serum and plasma. This study not only shed light onto the perturbed cellular pathways, but also began to reveal the presence of a distinct set of key metabolites that are selectively present or absent with respect to ALS2 mutations, laying the foundation for utilizing metabolites as potential biomarkers for a subset of ALS.
Highlights
Alsin is a 184 kDa protein of 1657 amino acid residues that is encoded by the ALS2 gene [1,2]
This report is presented almost as a case study of the patient a three-year-old female patient (AO), because metabolomic data were collected from her; her relatives; healthy male and female subjects; and DH, an age- and sex-matched amyotrophic lateral sclerosis (ALS) patient to AO with a different set of mutations in the ALS2 gene
Different from other metabolites, levunilic acid was present at high levels both in the serum and plasma of AO, while it remained undetected in the serum and plasma samples isolated from DH, all female and male controls, and the relatives of AO
Summary
Alsin is a 184 kDa protein of 1657 amino acid residues that is encoded by the ALS2 gene [1,2]. More than 100 pathogenic variants in ALS2 have been reported in patients with motor neuron diseases [3]. Recessive mutations in ALS2 gene lead to a spectrum of motor neuron disorders with a predominantly upper motor neuron (UMN) degeneration signature. These disorders are juvenile amyotrophic lateral sclerosis (JALS), juvenile primary lateral sclerosis (JPLS), and infantile-onset ascending hereditary spastic paraplegia (IAHSP) [1,2,5]. 82 patients with early-onset motor neuron diseases due to variants in ALS2 have been identified [3,7]. For JPLS, the average age of onset is 24 months, while for JALS, the average age of onset is 4.9 years
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
