{
  "abstract": "Background: Inborn errors of metabolism (IEMs) are a rare and often underrecognized cause of spastic paraplegia in children and adults.Owing to their high energy demands and long axons, motor neurons and the corticospinal tracts are particularly vulnerable to metabolic defects. Consequently, several potentially treatable neurometabolic disorders can mimic both pure and complex hereditary spastic paraplegia (HSP). Although spasticity is a shared hallmark, these disorders differ in their genetic etiology, metabolic profiles, clinical manifestations, and treatment responses.\n\nMethods: We investigated 10 Egyptian patients with spastic paraplegia as the core clinical feature using an integrated approach combining clinical assessment, biochemical profiling, and molecular diagnostics.\n\nResults: We identified (3) pathogenic, (4) VUS, and (4) likely pathogenic variants in nine disease-causing genes (SLC25A15, MTHFR, ARG1,OPA3, MOCS2, ETHE1, PANK2, C19orf12, and MTR), including eight homozygous and two compound heterozygous genotypes, with seven novel variants. Patients’ ages ranged from 1.9 to 17 years, with a median symptom onset of 1.8 years and median diagnosis age of 9.25 years. Most of the patients (80%) were born to consanguineous parents. Gait disturbance/spasticity was the most common presenting feature (90%; 100% respectively). Abnormal Metabolic profile was reported in (5/10, 50%).\n\nConclusion: Our findings highlight the value of integrated metabolic and genomic investigations in unexplained spastic paraparesis. Early molecular diagnosis enables precise disease identification, targeted therapy, and improved outcomes.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Medical Genetics, Faculty of Medicine, Ain Shams University, Cairo, Egypt",
    "Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ola A. Khalifa"
    },
    {
      "affs": [
        1
      ],
      "name": "Tarek M. Youssef"
    },
    {
      "affs": [
        0
      ],
      "name": "Radwa G. Mahmoud"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7wy9yvwrwqhr0.bib",
  "cited_by": 0,
  "doi": "10.3389/fgene.2026.1963118",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13735532/",
  "id": "7wy9yvwrwqhr0",
  "issns": [
    "1664-8021"
  ],
  "landing_url": "https://doi.org/10.3389/fgene.2026.1963118",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2804|Hereditary Neurological Disorders"
    ]
  ],
  "openalex": "W7223157395",
  "pdf_url": "https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2026.1963118/pdf",
  "pmcid": "PMC13735532",
  "pmid": "42991214",
  "published": "2026-10-22",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/7wy9yvwrwqhr0.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:21:12Z",
      "native_id": "PMC13735532",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fgene.2026.1963118"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2804|Hereditary Neurological Disorders",
      "subfield": "neuroscience"
    }
  ],
  "title": "Inherited metabolic diseases mimicking hereditary spastic paraplegia: a cohort of ten Egyptian patients",
  "title_text": "Inherited metabolic diseases mimicking hereditary spastic paraplegia: a cohort of ten Egyptian patients",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:21:12Z",
  "url": "https://research.draconitic.com/paper/7wy9yvwrwqhr0",
  "venue": "Frontiers in Genetics",
  "versions": []
}