Collapse, confusion, and clots: an acute presentation of late onset MTHFR deficiency, a treatable leukodystrophy
Bibliographic record
Abstract
A 29-year-old female of Pakistani-Indian origin presented with collapse and confusion on a background of 12 months of progressive leg weakness. Her medical history included significant psychiatric co-morbidity: initially bipolar affective disorder and depression, later revised to schizophrenia. On admission, she was encephalopathic with GCS 11(E3V3M5), and neurological examination revealed a moderate spastic paraparesis. CTPA demonstrated bilateral pulmonary emboli. Intracranial imaging showed extensive bilateral venous sinus thromboses with symmetrical parieto-occipital T2 hyperintensity suggestive of a leukodystrophy. Spinal imaging was normal. Metabolic testing revealed low- normal total B12 level 212ng/L(180-700ng/L), low folate 1.0ug/L(4.6-18.7ug/L), elevated homocysteine level 180umol/L(0-15umol/L), elevated MMA 340nmol/L(0-280nmol/L), and low methionine level 6umol/L on plasma amino acid profile- diagnostic of methylenetetrahydrofolate reductase (MTHFR) deficiency. Genetic testing confirmed likely pathogenic homozygous mutation, c.973C>T; Arg325Cys, in MTHFR with 20% residual MTHFR activity, and homozygous common polymorphism, c.6777C>T. Treatment included hydroxocobalamin, folinic acid, betaine and rivaroxaban alongside psychiatric management with no further deterioration in neurological deficit or further thromboses. Her siblings have been offered genetic testing. Homocysteine testing remains integral in young-onset stroke work-up. This case highlights the heterogenous adult presentation of treatable MTHFR deficiency. It is an important differential diagnosis in patients presenting with neuropsychiatric symptoms, spastic paraparesis, undifferentiated leukodystrophy, or thromboembolism.
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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 | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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".