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

Area of Science:

• Endocrinology
• Genetics
• Immunology

Background:

• Lipopolysaccharide-responsive beige-like anchor (LRBA) gene mutations are associated with primary immunodeficiency and autoimmune disorders.
• Monogenic diabetes, particularly autoimmune diabetes, can present in early infancy.

Observation:

• A 6-month-old patient presented with diabetic ketoacidosis, later diagnosed with compound heterozygous LRBA gene mutations.
• The patient developed autoimmune manifestations including arthritis, chronic diarrhea, and growth failure post-diagnosis.
• Bone marrow transplantation led to remission of diarrhea and arthritis, but not diabetes or growth failure.

Findings:

• LRBA gene mutations represent a rare etiology for autoimmune diabetes presenting in infancy.
• A hybrid closed-loop insulin delivery system (Minimed Medtronic 670G) demonstrated safety and efficacy in managing blood glucose.
• The patient maintained target blood glucose control (HbA1c 6%) without severe hypoglycemia.

Implications:

• This case highlights the importance of genetic testing for monogenic diabetes in infants with autoimmune features.
• LRBA deficiency should be considered in the differential diagnosis of early-onset autoimmune diabetes.
• Advanced insulin delivery systems can be beneficial for managing complex cases of pediatric autoimmune diabetes.