Early-onset type 1 diabetes mellitus in a child with a pathogenic CTLA4 variant complicated by generalized lipodystrophy and severe insulin resistance: a case report and literature review.

Authors

Yu Ding, Qun Li, Qianwen Zhang, Shiyang Gao, Juan Li, Lingwen Ying, Ru-En Yao, Tingting Yu, Xiumin Wang

Published in

Translational pediatrics. Volume 15. Issue 8. Pages 353. Aug 31, 2026. Epub Aug 24, 2026.

Abstract

The co-occurrence of early-onset type 1 diabetes mellitus (T1DM), acquired generalized lipodystrophy (AGL), and severe insulin resistance (SIR) is extremely rare, poses significant therapeutic challenges and no cases associated with pathogenic Cytotoxic T-lymphocyte-associated 4 (CTLA4) variants have been previously documented.
We performed genetic testing, flow cytometric immunophenotyping, leptin measurement and a 4.5-year clinical follow-up in a 3-year-3-month-old boy with early-onset T1DM, insulin allergy following initial insulin therapy, progressive lipodystrophy, SIR and mild hepatic dysfunction. We additionally conducted a systematic literature review to summarize CTLA4 variant-related autoimmune endocrine disorders and fat metabolism abnormalities. Pathological biopsy of subcutaneous adipose tissue revealed scattered lymphocytes and histiocytes infiltrating the fat septa and perivascular areas. A heterozygous pathogenic c.151C>T (p.Arg51*) variant in the CTLA4 gene was identified by whole-exome sequencing (WES) analysis. His father and sister carried the same variant with incomplete penetrance. The patient showed markedly reduced CTLA4 expression on regulatory T cells and undetectable serum leptin. Treatment with abatacept normalized liver function but did not improve glycemic control or insulin resistance. During the follow-up, the patient's growth consistently exceeded the 97th percentile for age and gender.
This report established the first association between a pathogenic CTLA4 variant and AGL, which expands the known clinical phenotypic spectrum of CTLA4-related immune dysregulation disorders. CTLA4 genetic testing should be considered in patients presenting with early-onset T1DM and unexplained lipodystrophy to enable early diagnosis and guide personalized management.

PMID:
42724548
Bibliographic data and abstract were imported from PubMed on 11 Sep 2026.

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