SUN-550 - Recognizing Maternally Inherited Diabetes and Deafness (MIDD): A Rare but Underdiagnosed Cause of Diabetes

Introduction: Maternally Inherited Diabetes and Deafness (MIDD) is a relatively uncommon and underdiagnosed cause of diabetes. The prevalence of MIDD can range from 0.5% to 2.8% of type 2 diabetics, if genetic testing is done. One reference even posited MIDD as being the most common syndromic form of diabetes (8%) in patients with confirmed monogenic forms of diabetes. Here, we present a patient with MIDD and discuss the causes and salient clinical features of MIDD to assist in its diagnosis.

Case Report: The patient is a 33-year-old female who presented at age 23 with hyperglycemia in the range of 200 to 300 on routine laboratory testing. She was placed on insulin initially by her local provider, with at least one ER visit due to hyperglycemia. Insulin was stopped and changed to sitagliptin and metformin at age 24. She was briefly off all medications for a few months without any diabetic ketoacidosis (DKA), with resumption of metformin at age 26. Her A1c has been in the 6.2 to 7 range. When seen in endocrine clinic, her weight was 90 lbs with a Body Mass Index (BMI) of 16. She also began having sensorineural hearing loss at age 30. Her labs showed C-peptide of 1.4 ng/mL with a corresponding glucose of 94 mg/dL, celiac antibody panel was negative, nutritional panel showed normal zinc and copper but low vitamin C of < 5 umol/L (range 23 - 114), other vitamins were normal, and lactic acid was normal. Due to her low BMI, lack of DKA without insulin, and presence of C-peptide and associated hearing loss, genetic testing for inborn errors of metabolism was done. It showed mutation in the MT-TL1 gene, m.3243A>G, at 46% heteroplasmy in the cells tested, diagnostic of MIDD.

Discussion: MIDD is caused by a mutation in the mitochondrial DNA (mtDNA) in a gene encoding a Leucine transfer RNA (MT-LT1). It is maternally transmitted. The phenotypic presentation is highly variable, even within the same family, related to heteroplasmy (amount of defective mtDNA) in the cells. In more severe cases, the mutation may lead to MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, Stroke-like episodes). The deafness is usually sensorineural and may precede the diabetes diagnosis. The clinical key points are: 1) Unusual clinical presentation (very low BMI, lack of DKA), 2) Presence of deafness, 3) Maternal mode of transmission with either the presence of diabetes or deafness. Although uncommon, recognition and proper diagnosis are essential to ensure proper treatment and adequate genetic counseling.

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