P-430: MODY 12 in a patient with autoimmune comorbidities: a diagnostic challenge - a case report
M L d O Cerqueira, M M M Lucena, G C Pinho, C A CoutinhoAbstract
Introduction
Maturity-Onset Diabetes of the Young (MODY) is a rare form of monogenic, non-autoimmune diabetes. MODY type 12, caused by mutations in the ABCC8 gene, is one of the least frequent subtypes.
Objectives
To describe a rare case of MODY 12 in a patient with multiple autoimmune comorbidities.
Methods
This is a descriptive, retrospective case report based on medical record review, conducted with legal guardian authorization.
Results
A female patient was diagnosed with autoimmune hepatitis at age 7, followed by alopecia areata. At age 8, she presented with classic symptoms of diabetes mellitus (polydipsia, polyphagia, nocturia, and weight loss), with a fasting plasma glucose of 324 mg/dL and glycated hemoglobin of 11.8%. Initial evaluation showed negative anti-insulin antibodies and inconclusive anti-islet cell antibodies. Family history included a mother with non-insulin-dependent diabetes (post-gestational) and a maternal aunt with insulin-dependent diabetes and neuropathic complications. Insulin therapy (NPH and Regular) was initiated at 1.4 IU/kg/day. During follow-up, an Inborn Error of Immunity (immunodysregulation phenotype) was suspected. After 31 months, a progressive reduction in insulin requirements was observed (to 0.32 IU/kg/day), associateed with frequent asymptomatic hypoglycemia, suggesting a non-autoimmune etiology. At age 13, whole-genome sequencing identified a pathogenic heterozygous variant in the ABCC8 gene, confirming MODY type 12. A transition to sulfonylurea (glibenclamide 5 mg/day) was performed.
Conclusions
This case highlights that comorbid autoimmune diseases can bias clinical reasoning toward Type 1 Diabetes, leading to MODY 12 underdiagnosis. A marked reduction in insulin requirements and recurrent hypoglycemia were red flags for genetic testing. Confirming the ABCC8 variant optimized prognosis, allowing a successful transition from insulin to effective oral therapy.