Acute onset of diabetes and rapid cognitive decline in a patient with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome

Abstract

Summary: Mitochondrial diseases are a group of rare diseases presenting with heterogeneous clinical, biochemical, and genetic disorders caused by mutations in the mitochondrial or nuclear genome. Multiple organs can be affected, particularly those with high energy demand. Diabetes is a common endocrine manifestation of mitochondrial diseases. The onset of mitochondrial diabetes can be latent or acute, and the presenting phenotype can be type 1- or type 2-like. Studies show that diabetes ais associated with latent progression of cognitive decline in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. Herein, we report a case of rapid cognitive decline after the acute onset of diabetes in a patient with MELAS syndrome. The patient was a 36-year-old woman who was hospitalized due to hyperglycemic crisis and seizures. She was diagnosed with MELAS syndrome two years previously, and had gradually progressing dementia and hearing loss. However, following the acute onset of diabetes, she developed rapid cognitive decline and loss of ability to perform daily activities. In conclusion, the acute onset of diabetes could be an associated risk factor for rapid cognitive decline in patients with MELAS syndrome. Thus, these patients as well as healthy carriers with related genetic mutations should undergo diabetes education and screening tests. Moreover, clinicians should be aware of the possibility for acute onset of hyperglycemic crisis, particularly in the presence of triggering factors.

Learning points: Diabetes is a common endocrine manifestation of mitochondrial diseases, presenting with a type 1- or type 2-like phenotype depending on the level of insulinopenia. Metformin should be avoided in patients with mitochondrial diseases to prevent metformin-induced lactic acidosis. Mitochondrial diabetes can manifest before or after the onset of MELAS syndrome. In patients with MELAS syndrome, diabetes can initially manifest with a life-threatening severe hyperglycemic crisis and can cause rapid cognitive decline. Diabetes screening tests (e.g. hemoglobin A1c, oral glucose tolerance test, or random blood glucose level measurement) should be performed either systematically or in the presence of symptoms, particularly after triggering events. Genetic testing and counseling should be provided to patients and their families for the purpose of better understanding the inheritance, progression, and possible outcomes of the disease.

Figure 1

Family pedigree. The index patient developed mitochondrial diabetes at the age of 36 years. Her mother, aunt, and uncle started taking oral antidiabetic drugs in mid-adulthood. Her sister and cousin required insulin therapy in their twenties.

Figure 2

MRI findings. Fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging (DWI) scans, and apparent diffusion coefficient (ADC) maps obtained A) on admission (March 2022) and B) after 1 month (April 2022). The initial FLAIR image shows only hyperintense edema in the left frontal lobe, while the follow-up scan also shows a left occipital lobe lesion (yellow arrows), with old lesions visible in the right occipital lobe on both scans (green arrow). DWI scans show cortical areas of restricted diffusion that are hyperintense on DWI and hypointense on ADC maps (yellow arrows), as well as subcortical vasogenic edema indicated by ADC hyperintense areas (red arrows). The two hemisphere lesions observed on the 2013, 2018, and 2020 scans became old lesions with partial encephalomalacia.