630 - Rare manifestations of immune mediated diseases linked with Marfan Syndrome - Case Presentation

Poster Number: 630
Publication Number: 630.3224

Background: Type 1 Diabetes Mellitus (TIDM) is an immune-mediated disorder characterized by chronic inflammation and destruction of the pancreatic islet cells. The United States CDC’s National Diabetes Statistics Report collected in 2020 recorded a diagnosis of T1DM in 187,000 children aged 20 and younger. Approximately 30% of patients with type 1 diabetes develop poly autoimmunity, most commonly, thyroid dysfunction (15-30%), gastritis (5-10%), celiac disease (4-9%) and vitiligo (2-10%) (1). Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder caused by a mutation in the Fibrillin –1 (FBN-1) gene with systemic involvement. It has an incidence of 1 in 5,000 and is the most common monogenetic connective tissue disorder.

Objective: The aim of our presentation is the description of a case of new onset Type 1 Diabetes with pre-existing Hashimoto’s and Marfan Syndrome.

Design/Methods:

Case Presentation: A 17-year-old male with new onset T1DM presented with unintentional weight loss, polyuria, polydipsia, abdominal pain, and lethargy, after a respiratory illness. Patient diagnosed with Hashimoto's thyroiditis and Marfan’s within the past year. Patient met criteria for MFS based on cardiac complication (Mitral Valve Prolapse) in conjunction with a systemic score of 8. Hashimoto's confirmed with high TSH: 4.47 ng/mL (range 0.50-4.30), normal total T4, and positive thyroid antibodies.

Results: The association of MFS with autoimmune pathologies is rare, but its multimorbidity with autoimmune diseases, most notably diabetes and thyroiditis, has been identified in several case reports (2-5). Disease-causing mutations in FBN-1, the gene associated with MFS, results in increased signaling of transforming growth factor beta cytokines (TGF-B) (6). TGF-B proteins are involved in several different components of the immune response pathway/ complement system. Human leukocyte antigen (HLA) is the main genetic factor related to autoimmune diseases and may play a key role in understanding disease susceptibility.

Conclusion(s): Further research is warranted to determine if there is a direct link between MFS and immune-mediated disorders. Additional research regarding hereditary and environmental markers, such as the mechanism between increased signaling by TGF-B and pathogenic FBN-1 mutations (3) or HLA expression to autoimmune disease in relation to MFS is substantiated. This may be instrumental in early detection, development of disease-focused treatment, reduction in multi-disease progression and reducing long term complications.