Evidence map›Paper›PMID 40887432›Full record

ArticleDiabetic medicine : a journal of the British Diabetic Association2025

Neonatal diabetes mellitus is a significant feature of COXPD-24 caused by recessive NARS2 variants.

Russell Donis, Matthew N Wakeling, Nicola Jeffery, Molly Govier, Matthew B Johnson, Samar Sabir Hassan, Mohammed Ahmed Abdullah, Khadiga Yehia Elsayed Eltonbary, Nima Parvaneh, Mahsa M Amoli and 9 more

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In one paragraph

Article in Diabetic medicine : a journal of the British Diabetic Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Neonatal diabetes mellitus is a significant feature of COXPD-24 caused by recessive NARS2 variants.Diabetic medicine : a journal of the British Diabetic Association · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Russell DonisDepartment of Clinical and Biomedical Science, University of Exeter Medical School, Exeter, UK.
Matthew N WakelingDepartment of Clinical and Biomedical Science, University of Exeter Medical School, Exeter, UK.
Nicola JefferyDepartment of Clinical and Biomedical Science, University of Exeter Medical School, Exeter, UK.
Molly GovierDepartment of Clinical and Biomedical Science, University of Exeter Medical School, Exeter, UK.
Matthew B JohnsonDepartment of Clinical and Biomedical Science, University of Exeter Medical School, Exeter, UK.
Samar Sabir HassanDepartment of Pediatric Endocrinology, Gaafar Ibn Auf Pediatric Tertiary Hospital, Khartoum, Sudan.
Mohammed Ahmed AbdullahDepartment of Pediatric Endocrinology, Gaafar Ibn Auf Pediatric Tertiary Hospital, Khartoum, Sudan.
Khadiga Yehia Elsayed EltonbaryDepartment of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Nima ParvanehDivision of Allergy and Clinical Immunology, Pediatrics Center of Excellence, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Mahsa M AmoliMetabolic Disorders Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Farzaneh AbbasiDr. Sami Ulus Children's Training and Research Hospital, Clinic of Pediatric Endocrinology, Ankara, Turkey.
Selin ElmaoğullarıDr. Sami Ulus Children's Training and Research Hospital, Clinic of Pediatric Endocrinology, Ankara, Turkey.
Semra ÇetinkayaDr. Sami Ulus Children's Training and Research Hospital, Clinic of Pediatric Endocrinology, Ankara, Turkey.
Kubra GunesDepartment of Pediatrics, Tokat State Hospital, Tokat, Turkey.
Meltem TayfunSincan Eğitim Araştırma Hastanesi Pediatric Endocrinology Department, Ankara, Turkey.
Hanieh YaghootkarJoseph Banks Laboratories, College of Health and Science, University of Lincoln, Lincoln, UK.
Andrew T HattersleyDepartment of Clinical and Biomedical Science, University of Exeter Medical School, Exeter, UK.
Sarah E FlanaganDepartment of Clinical and Biomedical Science, University of Exeter Medical School, Exeter, UK.
Elisa De FrancoDepartment of Clinical and Biomedical Science, University of Exeter Medical School, Exeter, UK.ORCID https://orcid.org/0000-0002-1437-7891

Funding

Diabetes UKEuropean Foundation for the Study of DiabetesNovo Nordisk FondenWellcome Trust
6 · The paper itself

Abstract

backgroundRecessive loss-of-function NARS2 variants causing the multi-system disorder Combined oxidative phosphorylation deficiency 24 (COXPD24) have recently been reported in 3 individuals with diabetes diagnosed between 3 days and 14 months of age. In this study, we investigate the presence of NARS2 variants in a large cohort of individuals with early-onset diabetes.

methodsWe used genome and targeted next-generation sequencing to screen for rare, coding biallelic NARS2 variants in a cohort of 397 individuals diagnosed with diabetes <24 months of age of unknown genetic cause.

resultsWe identified 8 individuals with homozygous disease-causing missense variants in NARS2 (4 individuals with the p.(Phe216Leu) variant, 3 with p.(Thr180Asn) and one with p.(Val440Leu)). All 8 individuals were diagnosed with insulin-dependent diabetes before 6 months of age (neonatal diabetes, NDM) with the median age at diagnosis being 4 weeks (range: 1 to 20 weeks). 7/8 probands had low birthweight (median Z-score: -2.43, range: -4.17 to 0.86). Neurological features were common, with epilepsy and developmental delay each identified in 7/8 and 6/8 participants, respectively.

conclusionTaken together with previously published cases, this study shows that NDM is an important feature of COXPD-24 and highlights a critical role for NARS2 in the insulin-secreting pancreatic β-cell.

Indexed as

Diabetes MellitusDiabetes Mellitus, Type 1Infant, Newborn, DiseasesCohort StudiesFemaleGenes, RecessiveHumansInfantInfant, NewbornMaleMutation, Missensemitochondriamitochondrial diseasemitochondrial dysfunctionmonogenic diabetesNARS2neonatal diabetes mellitusβ‐Cells

Identifiers

PMID40887432
PMCPMC12535310

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.