Stealthy progression of type 2 diabetes mellitus due to impaired ketone production in an adult patient with multiple acyl-CoA dehydrogenase deficiency

• Published in: Molecular genetics and metabolism reports 2024-03, Vol.38, p.101061, Article 101061
• Main Authors: Ikeda, Nodoka, Wada, Yoichi, Izumi, Tomohito, Munakata, Yuichiro, Katagiri, Hideki, Kure, Shigeo
• Format: Article
• Language: English
• Subjects: Case Report; Diabetic ketoacidosis; Multiple acyl-CoA dehydrogenase deficiency; Type 2 diabetes mellitus
• ISSN: 2214-4269; 2214-4269
• DOI: 10.1016/j.ymgmr.2024.101061

Multiple acyl-CoA dehydrogenase deficiency (MADD) is an inherited metabolic disorder caused by biallelic pathogenic variants in genes related to the flavoprotein complex. Dysfunction of the complex leads to impaired fatty acid oxidation and ketone body production which can cause hypoketotic hypoglycemia with prolonged fasting. Patients with fatty acid oxidation disorders (FAODs) such as MADD are treated primarily with a dietary regimen consisting of high-carbohydrate foods and avoidance of prolonged fasting. However, information on the long-term sequelae associated with this diet have not been accumulated. In general, high-carbohydrate diets can induce diseases such as type 2 diabetes mellitus (T2DM), although few patients with both MADD and T2DM have been reported. 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 over 2 months. Laboratory tests revealed a HbA1c level of 13.9%; however, the patient did not show metabolic acidosis but only mild ketosis. 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 due to their inability to produce ketone bodies. These findings warrant further research of the long-term complications associated with this diet as well as warning of the potential progression of diabetes in patients with FAODs such as MADD.