An Unreported homozygous variant within Lipopolysaccharide responsive beige-like anchor (LRBA) gene in a child exhibiting with infantile type 1 diabetes mellitus

Abstract

We report a patient who was born at term as the first son of consanguineous Saudi parents. He developed IDDM at the age of 7 months; the initial symptoms included fever and vomiting. The laboratory findings indicated pronounced ketoacidosis, initial fluid replacement with normal saline, followed by continuous IV insulin infusion. After a while, the baby was out of DKA. Our endocrinologist advised us to start administering S/C insulin NPH 1 unit BID. Fortunately, we suspected a primary immune deficiency acer a few days from the first presentation. The WES revealed A homozygous likely pathogenic variant was identified in the LRBA gene. The result is consistent with a genetic diagnosis of autosomal recessive CVID type 8 with autoimmunity. The LRBA protein regulates the expression of CTLA-4, which is a potent immune checkpoint receptor expressed by activated and regulatory by the T-cells. CTLA-4 blocks the stimulation/proliferation of T-cells and modulates immune responses.