ESPE Abstracts

Objectives: Diabetes mellitus (DM) as part of autoimmune dysregulation syndromes holds a unique place among DM monogenic forms. Early diagnosis of the disease is critical for pathogenetic therapy to be prescribed. We describe a clinical case of insulin-dependent DM in combination with severe autoimmune enteropathy in a young patient who had a novel compound heterozygous mutation in the LRBA gene.

Methods: The patient underwent clinical-laboratory and genetic examinations at the Russian Children's Clinical Hospital' Immunology Department in Moscow.

Results: A 2.5-year-old patient was admitted to the hospital in critical condition, complaining of frequent loose stools, vomiting and weight loss. His blood pH was 7.19, his VE was 18.5 mmol/l, and his glucose level was 11.9 mmol/l. The child's early development was normal, and hereditary endocrine diseases were not aggravated. As early as 10 months old, he began showing signs of insulin-dependent DM. Beginning at 1 year and 11 months, the patient experienced several episodes of vomiting and frequent loose stools, which eventually led to the development of acute diabetic ketoacidosis (DKA) and inpatient admission to the intensive care unit. Seronegative celiac disease, infectious enterocolitis, and Crohn's disease were all considered in the differential diagnosis. Cytopenia was discovered during the examination. According to the immunological examination, the numbers of lymphocytes and serum immunoglobulin subpopulations were in the normal range. FOXP3 expression was at the lower limit of the normal range. Because the therapy had no effect, a male child with early signs of enteropathy and insulin-dependent diabetes was suspected of having the IPEX syndrome. The entire exome was sequenced, and previously uncharacterized heterozygous mutations in the LRBA gene were found, i.e.: NM 006726.4: c.1028G>A (p.Cys343Tyr) and c.7561dupA (p.Thr2521Asnfs). His diagnosis was as follows: Primary immunodeficiency. Immune dysregulation syndrome: Diabetes mellitus. Autoimmune enteropathy. Autoimmune cytopenia. Targeted therapy with Abatacept at a dose of 10 mg/kg/day was prescribed to him, and the results showed that it had a positive effect.

Conclusion: This clinical case demonstrates the difficulties in diagnosing IPEX-like syndrome in young children due to the rarity of this pathology, the nonspecific clinical picture that occurs in these patients, and the need for a multidisciplinary approach to the management of such patients. Genetic validation of the diagnosis is required for differential diagnosis with IPEX syndrome and other IPEX-like syndromes, as well as for the selection of the most effective patient management tactics.