Anti-GAD antibody-negative, anti-IA2 antibody-positive slowly progressive insulin-dependent diabetes mellitus and Graves' disease preceded by childhood-onset minimal change nephrotic syndrome: a case report.

Abstract

It is rare for a patient to have minimal change nephrotic syndrome, slowly progressive insulin-dependent diabetes mellitus, and Graves' disease in combination. In this case, a patient developed idiopathic nephrotic syndrome at the age of 11 years. She was diagnosed with frequently relapsing nephrotic syndrome and steroid-dependent nephrotic syndrome after repeated increases in urinary protein levels with prednisolone reduction. At the age of 14 years, steroid-induced diabetes was suspected because she was negative for anti-glutamic acid decarboxylase (GAD) antibody, and her glycemic control improved after medication. At the age of 16 years, her nephrotic syndrome was in remission, but even after discontinuation of cyclosporine, her glycemic control did not improve. Decreased insulin secretion and positive anti-insulinoma-associated protein-2 (IA2) antibody were found, and therefore she was diagnosed as having slowly progressive insulin-dependent diabetes mellitus (SPIDDM). Although her glycemic control was stable with insulin therapy, she was diagnosed with asymptomatic Graves' disease at the age of 28 years and started treatment. Human leukocyte antigen testing (HLA) was performed to evaluate the etiology of the disease, which revealed A*02:01, B*35:01, DQA1*03:01, DQB1*03:02, DQB1*04:01, DRB1*04:05, DRB1*08:02, and DPB1*05:01, suggesting genetic involvement of HLA for each disease susceptibility.