Three siblings with nonketotic hyperglycinaemia, mildly elevated plasma homocysteine concentrations and moderate methylmalonic aciduria
Bibliographic record
Abstract
Nonketotic hyperglycinaemia (NKH) (McKusick 238300, 238310, 238330) is a rare autosomal recessive disease caused by defects in the glycine cleavage system (GCS ; EC 2.1.2.10 and EC 1.4.4.2), which is located in the inner mitochondrial membrane of the liver, kidney, brain and placenta (Hamosh et al 1995).The GCS catalyses the formation of ammonia, carbon dioxide, methylenetetrahydrofolate and NADH ] H`from glycine, tetrahydrofolate, NAD`and water.Evidence for a disease-associated interference with the metabolism of single-carbon units in the central nervous system has recently been reported in a study demonstrating mildly elevated CSF homocysteine levels in NKH (Van Hove et al 1998).Various coenzyme A (CoA) derivatives including propionyl-CoA and methylmalonyl-CoA were found to inhibit the hepatic GCS, thus causing secondary hyperglycinaemia if they accumulate in organic acidaemias (Hayasaka and Tada 1983).In contrast to NKH, CSF and brain glycine content are normal in these disorders of " ketotic hyperglycinaemia Ï (Perry et al 1975).Interestingly, although propionate and methylmalonate metabolism was originally reported to be normal in NKH (Baumgartner et al 1975), one case of NKH associated with propionic aciduria has been published (Farriaux et al 1976).We report three siblings with neonatal NKH, two girls and a boy, who are the Ðrst, fourth and Ðfth children born to healthy Ðrst-cousin Arab parents.Two other children of the family are healthy.The Ðrst child, a girl (patient 1), was admitted to our hospital at age of years and presented with severe psychomotor and mental 71 2 retardation, marked hypotonia and occasional Ðts.She had a history of hypotonia and feeding difficulties from birth, as well as of seizures starting in the second month of life.Glycine concentrations were normal in plasma (273 kmol/L, normal 127È341) but elevated in CSF (49.5 kmol/L normal \15) and urine (670 kmol/mmol creatinine, normal \500) giving a CSF/plasma glycine ratio of 0.181 (normal \0.08).Liver glycine cleavage enzyme activity was from non-detectable to 0.04 nmol/h per mg protein (normal range 2.1È11.9) in repeat assays.The fourth child of the family, a girl (patient 2), was diagnosed at the age of 16 months.She was born at 35 weeks gestational age as a second twin and presented with marked generalized hypotonia
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".