Parkinsonism in GTP cyclohydrolase 1-deficient DOPA-responsive dystonia
Bibliographic record
Abstract
Sir, We read with great interest the article entitled ‘Parkinson’s disease in GTP cyclohydrolase 1 mutation carriers’ published recently by Mencacci et al. (2014); the enzyme GTP cyclohydrolase 1, encoded by the GCH1 gene, catalyzes the rate-limiting step in the biosynthesis of tetrahydrobiopterin (the essential cofactor for tyrosine hydroxylase). Using 123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) tropane, the authors found abnormal imaging of dopamine transporter (DAT) single photon emission computed tomography (SPECT) in four adult-onset parkinsonian patients associated with GCH1 variants from four unrelated pedigrees with autosomal dominant GTP cyclohydrolase 1-deficient DOPA-responsive dystonia [DYT5a; the major form of DOPA-responsive dystonia (Furukawa et al., 2013)]. In addition, analysing whole-exome sequencing data of 1318 parkinsonian and 5935 control cases, the authors identified 11 different heterozygous GCH1 variants and have stated that rare GCH1 mutations are associated with an increased risk of Parkinson’s disease. Consequently, they have suggested that normal striatal 18F-fluorodopa uptake reported previously in patients with GCH1-parkinsonian phenotype (Nygaard et al., 1992; Furukawa et al., 2013) may result from compensatory upregulation and that there seems to be nigrostriatal dopaminergic denervation in these patients.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.008 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.007 | 0.007 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".