Case Report: Infantile-Onset Fulminant Type 1 Diabetes Mellitus Caused by Novel Compound Heterozygous LRBA Variants

Eriko Totsune, Tomohiro Nakano, Kunihiko Moriya, Daichi Sato, Dai Suzuki, Akinobu Miura, Saori Katayama, Hidetaka Niizuma, Junko Kanno, Menno C. van Zelm, Kohsuke Imai, Hirokazu Kanegane, Yoji Sasahara, Shigeo Kure

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)


Lipopolysaccharide-responsive beige-like anchor (LRBA) deficiency is a subtype of common variable immune deficiency (CVID). Numerous case reports and cohort studies have described a broad spectrum of clinical manifestations and variable disease phenotypes, including immune dysregulation, enteropathy, and recurrent infections. Although LRBA deficiency is an autosomal recessive primary immunodeficiency resulting in a phenotype similar to CVID, it is a monogenic disease and separate from CVID. Recently, in a report of monogenic primary immunodeficiency disorder associated with CVID and autoimmunity, the most common mutated gene was LRBA. We report the case of a girl who presented with fulminant type 1 diabetes at age 7 months. She later experienced recurrent bacterial infections with neutropenia and idiopathic thrombocytopenic purpura. Clinical genome sequencing revealed compound heterozygosity of the LRBA gene, which bore two novel mutations. A genetic basis should be considered in the differential diagnosis for very young patients with fulminant autoimmunity, and the diagnostic work-up should include evaluation of markers of immunodeficiency.

Original languageEnglish
Article number677572
Number of pages8
JournalFrontiers in Immunology
Publication statusPublished - 12 Apr 2021


  • CTLA-4 deficiency
  • infantile-onset fulminant type 1 diabetes mellitus
  • LRBA deficiency
  • refractory autoimmune cytopenia
  • transposable elements (TE)

Cite this