Recognition of Hyperinsulinaemic Hypoglycaemia in Infants with Congenital Central Hypoventilation Syndrome
Bibliographic record
Abstract
INTRODUCTION: Congenital central hypoventilation syndrome (CCHS) is a rare autosomal dominant condition due to mutations in the transcription factor PHOX2B. It is characterized by alveolar hypoventilation with symptoms of autonomic nervous system dysfunction. Hyperinsulinaemic hypoglycaemia (HH) due to glucose dysregulation caused by anomalous insulin secretion has been reported as a feature of CCHS. However, HH and glycaemic outcomes in the context of CCHS have not been characterized in longitudinal follow-up. We describe the variable phenotype of glucose dysregulation and glycaemic outcomes in children with CCHS. CASE PRESENTATION: We report 6 children with PHOX2B mutation-positive CCHS diagnosed with HH in a national cohort from two UK congenital hyperinsulinism specialist centres. We describe the initial presentation, the challenges in management, and glycaemic outcomes in longitudinal follow-up. All patients were term infants diagnosed with CCHS in the neonatal period due to PHOX2B mutations and required long-term ventilation by tracheostomy. HH was diagnosed at a median age of 222 days (median, range 36-594) with postprandial hypoglycaemia (4/6 patients) or fasting hypoglycaemia (2/6 patients). Two patients were treated with diazoxide monotherapy; one with diazoxide and overnight continuous gastrostomy feeds; one with acarbose; and two with dietary manifestations and use of continuous glucose monitoring sensor. Three patients who presented earlier in the observation period demonstrated a reduction in the severity of HH over time, leading to hypoglycaemia resolution at a median age of 4.8 years (range 4.45-5.5 years). CONCLUSION: Patients with CCHS, due to PHOX2B mutations, may experience both fasting and postprandial hypoglycaemia, necessitating treatment for HH. Clinicians should screen children with CCHS for hypoglycaemia symptoms to quickly identify those affected by HH, initiate prompt treatment, and prevent potential brain injury from severe hypoglycaemia. The severity of hypoglycaemia due to HH tends to decrease over time, with glycaemic resolution potentially being achieved over several years.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.004 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".