{
  "abstract": "Tyrosine hydroxylase (TH) deficiency is a rare metabolic disorder caused by biallelic pathogenic variants in the TH gene (TH). More than 95% of TH variants can be detected by usual sequence analyses and gene-targeted deletion/duplication analyses are necessary to identify gross abnormalities (e.g., exon deletions). The enzyme TH, a tetrahydrobiopterin (BH4)-dependent monooxygenase, catalyzes the rate-limiting step in catecholamine biosynthesis. Thus, symptoms result from dopamine deficiency and subsequent noradrenaline/adrenaline deficits, and most patients demonstrate positive response to levodopa. The phenotypic spectrum of this treatable disorder is extremely broad. Although the underlying mechanisms of phenotypic heterogeneity are still unknown, recent human and experimental data have indicated that 1) there is no dopaminergic neuronal degeneration in TH deficiency, 2) mildly affected patients may develop dopa-responsive dystonia through dysfunctional D1 dopamine receptors due to congenital dopamine deficiency and insufficient postnatal dopamine increases in the striatum, and 3) severely affected patients may demonstrate remarkable motor development delay in infancy and hypersensitivity to levodopa therapy (leading to levodopa-induced dyskinesias) caused by profound brain dopamine deficit and consequent abnormal synaptic and brain maturation. It is known that, in the normal human brain, development of the nigrostriatal dopaminergic system is incomplete at birth and striatal dopamine, TH, and its cofactor BH4 concentrations significantly increase during postnatal development. Therefore, dopamine deficiency should be corrected by appropriate treatment with levodopa (e.g., very low initial doses for severely affected cases to avoid intolerable levodopa-induced dyskinesias) as soon as genetically diagnosed or upon the appearance of characteristic symptoms of TH deficiency.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 1,
  "authors": [
    {
      "name": "YOSHIAKI FURUKAWA"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9jwwhb66drfa5.bib",
  "cited_by": 0,
  "doi": null,
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13725223/",
  "id": "9jwwhb66drfa5",
  "issns": [
    "2759-7504"
  ],
  "landing_url": "https://europepmc.org/article/MED/42973816",
  "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",
      "Reviews"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://europepmc.org/articles/PMC13725223?pdf=render",
  "pmcid": "PMC13725223",
  "pmid": "42973816",
  "published": "2026-10-07",
  "publisher": "Juntendo Medical Society",
  "ris": "https://research.draconitic.com/paper/9jwwhb66drfa5.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:23:39Z",
      "native_id": "PMC13725223",
      "source": "pmc",
      "url": null
    },
    {
      "first_seen": "2026-11-04T15:20:49Z",
      "native_id": "MED:42973816",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42973816"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "journal-openalex:F27",
      "subfield": "general"
    }
  ],
  "title": "Tyrosine Hydroxylase Deficiency: From Clinical and Therapeutic Features to Pathogenetic Considerations",
  "title_text": "Tyrosine Hydroxylase Deficiency: From Clinical and Therapeutic Features to Pathogenetic Considerations",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:21:32Z",
  "url": "https://research.draconitic.com/paper/9jwwhb66drfa5",
  "venue": "Juntendo Medical Journal",
  "versions": []
}