IL2RA – Neonatal Diabetes Mellitus

In two unrelated patients with early-onset diabetes, biallelic loss-of-function variants in IL2RA were identified, consistent with an autosomal recessive mode of inheritance. One proband harbored a homozygous nonsense variant c.227G>A (p.Trp76Ter) (PMID:38408297) and another was genetically diagnosed in a consanguineous pedigree (PMID:35662751). Both presented with insulin-dependent hyperglycaemia before 6 months of age and features of immune dysregulation. No additional segregation data or recurrence of these alleles in other families have been reported, supporting a Limited level of clinical validity for the gene–disease association with neonatal diabetes mellitus.

There are no published functional assays directly linking IL-2Rα deficiency to pancreatic β-cell failure or altered glucose metabolism in these patients. While IL2RA is critical for regulatory T-cell homeostasis, its precise mechanistic role in neonatal diabetes remains uncharacterized. Future studies in cellular or animal models of IL2RA deficiency in the context of β-cell autoimmunity would help confirm pathogenicity. Key Take-home: IL2RA should be included in gene panels for neonatal diabetes, especially when immune dysregulation is evident, but current evidence supports only a Limited contribution to autosomal recessive neonatal diabetes.

References

• Indian journal of endocrinology and metabolism | 2022 | Genetic Heterogeneity and Challenges in the Management of Permanent Neonatal Diabetes Mellitus: A Single-Centre Study from South India. PMID:35662751
• • • Title unavailable PMID:38408297

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