{
  "abstract": "Background: Ornithine transcarbamylase deficiency (OTCD) demonstrates marked phenotypic heterogeneity, ranging from severe neonatal hyperammonaemia to asymptomatic disease. While acute hyperammonaemic crises are well recognised, the long-term burden in medically managed, non-transplanted individuals across the phenotypic spectrum remains incompletely defined. This study aimed to characterise longitudinal clinical outcomes and disease burden in a multicentre cohort and to explore genotype–phenotype relationships.\n\nResults: Forty-five individuals were included (27 decompensated: 26 late-onset and 1 neonatal-onset; 18 non-decompensated), with median age at last follow-up of 13.3 years (IQR, 7.8–17.7). Molecular confirmation was available in 40/45 (88.9%). Among the decompensated cohort, 111 hyperammonaemic decompensation episodes, 224 hospital admissions, and 70 episodes requiring intravenous nitrogen-scavenger rescue were recorded; 16/26 (61.5%) late-onset individuals experienced recurrent decompensations. Individuals without documented decompensation also demonstrated clinically relevant morbidity, including behavioural problems (38.9%), recurrent vomiting (44.4%), chronic fatigue (33.3%), and learning difficulties (16.7%).\n\nConclusion: In this multicentre cohort of non-transplanted individuals, OTCD was associated with substantial morbidity across the phenotypic spectrum. Late-onset disease was characterised by recurrent metabolic instability, frequent hospitalisation, and neurodevelopmental burden, while individuals without overt hyperammonaemic episodes also experienced clinically relevant symptoms. These findings highlight that clinically relevant disease burden extends across the OTCD phenotypic spectrum. Improved risk stratification and disease-modifying therapies remain important unmet needs.",
  "abstract_shown": true,
  "affiliations": [
    "Genetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College London, London, WC1N 1EH UK",
    "Department of Paediatric Inherited Metabolic Disease, Evelina Children’s Hospital, Guy’s, and St Thomas’ NHS Foundation Trust, London, SE1 7EH UK",
    "Department of Paediatric Metabolic Medicine, Great Ormond Street Hospital for Children NHS Foundation Trust, London, WC1N 3JH UK",
    "Department of Adult Inherited Metabolic Disease, Guy’s and St Thomas’ NHS Foundation Trust, London, SE1 7EH UK",
    "Dietetics, Great Ormond Street Hospital for Children NHS Foundation Trust, London, WC1N 3JH UK",
    "Willink Unit, Manchester Academic Health Sciences Centre, Genomic Medicine, Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester, M13 9WL UK"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 27,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Berna Seker-Yilmaz",
      "orcid": "0000-0003-0425-0341"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Julien Baruteau"
    },
    {
      "affs": [
        3
      ],
      "name": "Raphael Buttigieg"
    },
    {
      "affs": [
        2
      ],
      "name": "Anupam Chakrapani"
    },
    {
      "affs": [
        1
      ],
      "name": "Michael Champion"
    },
    {
      "affs": [
        1
      ],
      "name": "Catherine Davies"
    },
    {
      "affs": [
        2
      ],
      "name": "James Davison"
    },
    {
      "affs": [
        4
      ],
      "name": "Marjorie Dixon"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Sherry Fang"
    },
    {
      "affs": [
        2
      ],
      "name": "Emma Footitt"
    },
    {
      "affs": [
        1
      ],
      "name": "Joanna Gribben"
    },
    {
      "affs": [
        2
      ],
      "name": "Stephanie Grunewald"
    },
    {
      "affs": [
        1
      ],
      "name": "Gemma Hack"
    },
    {
      "affs": [
        5
      ],
      "name": "Thomas Hartley"
    },
    {
      "affs": [
        1
      ],
      "name": "Hugh Lemonde"
    },
    {
      "affs": [
        0
      ],
      "name": "Philippa Mills"
    },
    {
      "affs": [
        5
      ],
      "name": "Andrew A. M. Morris"
    },
    {
      "affs": [
        1
      ],
      "name": "Helen Mundy"
    },
    {
      "affs": [
        1
      ],
      "name": "Dinusha Pandithan"
    },
    {
      "affs": [
        3
      ],
      "name": "Radha Ramachandran"
    },
    {
      "affs": [
        2
      ],
      "name": "Siyamini Sivananthan"
    },
    {
      "affs": [
        5
      ],
      "name": "Chern Tan"
    },
    {
      "affs": [
        5
      ],
      "name": "Dexter Tarr"
    },
    {
      "affs": [
        4
      ],
      "name": "Louise Van Dorp"
    },
    {
      "affs": [
        1
      ],
      "name": "Roshni Vara"
    },
    {
      "affs": [
        1
      ],
      "name": "Abigail Woodward"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Paul Gissen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/djyqgbq6bszmk.bib",
  "cited_by": 0,
  "doi": "10.1186/s13023-026-04517-w",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13715288/",
  "id": "djyqgbq6bszmk",
  "issns": [
    "1750-1172"
  ],
  "landing_url": "https://doi.org/10.1186/s13023-026-04517-w",
  "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",
      "Research"
    ],
    [
      "openalex",
      "1308|Metabolism and Genetic Disorders"
    ]
  ],
  "openalex": "W7171546341",
  "pdf_url": null,
  "pmcid": "PMC13715288",
  "pmid": "42947220",
  "published": "2026-07-28",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/djyqgbq6bszmk.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T12:22:38Z",
      "native_id": "PMC13715288",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s13023-026-04517-w"
    }
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1308|Metabolism and Genetic Disorders",
      "subfield": "general"
    }
  ],
  "title": "Longitudinal outcomes of non-transplanted ornithine transcarbamylase deficiency in males and females: a multicentre UK natural history cohort",
  "title_text": "Longitudinal outcomes of non-transplanted ornithine transcarbamylase deficiency in males and females: a multicentre UK natural history cohort",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:22:38Z",
  "url": "https://research.draconitic.com/paper/djyqgbq6bszmk",
  "venue": "Orphanet Journal of Rare Diseases",
  "versions": []
}