Early-Onset Diabetes in an Infant with a Novel Frameshift Mutation in LRBA

Abstract

We describe early-onset diabetes in a 6-month-old patient carrying an LRBA gene mutation. Mutations in this gene cause primary immunodeficiency with autoimmune disorders in infancy. At admission, he was in diabetic ketoacidosis, and treatment with fluid infusion rehydration and then i.v. insulin was required. He was discharged with a hybrid closed-loop system for insulin infusion and prevention of hypoglycemia (Minimed Medtronic 670G). He underwent a next-generation sequencing analysis for monogenic diabetes genes, which showed that he was compound heterozygous for two mutations in the LRBA gene. In the following months, he developed arthritis of hands and feet, chronic diarrhea, and growth failure. He underwent bone marrow transplantation with remission of diarrhea and arthritis, but not of diabetes and growth failure. The blood glucose control has always been at target (last HbA1c 6%) without any severe hypoglycemia. LRBA gene mutations are a very rare cause of autoimmune diabetes. This report describes the clinical course in a very young patient. The hybrid closed-loop system was safe and efficient in the management of blood glucose. This report describes the clinical course of diabetes in a patient with a novel LRBA gene mutation.

Keywords: LRBA; bone marrow transplantation; early-onset diabetes; hybrid closed-loop; primary immunodeficiency.

Figure 1

LRBA schematic protein domains map and location of the identified mutations. ConA-like: conconavalin A-like domain (186–371, 186 aa). PH: PH Pleckstrin homology domain (2073–2181, 109aa). BEACH: BEACH domain of Beige and Chediak-Higashi. WD40: WD40 repeat-like containing domain. Of the two identified mutations, the novel one is indicated in red text. The currently known disease-causing LRBA mutations are available on Human Genome Mutation Database at https://my.qiagendigitalinsights.com/bbp/view/hgmd/pro/start.php (accessed on 1 September 2021).