Challenging diagnosis of type 2 diabetes mellitus in patient with multiple acyl-CoA dehydrogenase deficiency

Background: Multiple acyl-CoA dehydrogenase deficiency (MADD) is an inherited metabolic disorder caused by biallelic mutations in genes related to the flavoprotein complex. The dysfunction of the complex leads to impaired fatty acid oxidation and ketone body production, which can easily cause hypoketotic hypoglycemia with prolonged fasting. Therefore, patients with fatty acid oxidation disorders (FAODs) such as MADD are treated with a specific dietary regimen consisting of high-carbohydrate, low-fat, and low-protein meals, and prolonged fasting is avoided. However, the long-term sequelae associated with this dietary regimen have not been fully understood. High-carbohydrate diets induce lifestyle diseases such as type 2 diabetes mellitus (T2DM) although few patients with both MADD and T2DM have been reported.

Case report: We present the case of a 32-year-old man with MADD who was on a high-carbohydrate diet for >30 years and exhibited symptoms resembling diabetic ketoacidosis. He presented with polydipsia, polyuria, and weight loss, with a decrease in body mass index from 31 to 25 kg/m2 in 2 months. Laboratory tests revealed hemoglobin A1C level of 13.9%, and the patient was diagnosed with T2DM. However, the patient did not show metabolic acidosis but only mild ketosis.

Discussion/Conclusion: This report emphasizes the potential association between long-term adherence to high-carbohydrate dietary therapy and T2DM development. Moreover, this case underscores the difficulty of detecting diabetic ketosis in patients with FAODs such as MADD because of their inability to produce ketone bodies. These findings warrant further research into the long-term complications of treatment and a better understanding of the clinical presentations of the complications in patients with FAODs.