Late-Onset Melas with Midd: An Uncommon Age of Presentation

Abstract

Objective: Maternally inherited diabetes and deafness (MIDD) is a rare form of diabetes caused by a mutation in mitochondrial DNA, usually a point mutation at position 3243 in the leucine tRNA gene. This same mutation can cause a rare but severe syndrome called mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS).Methods: We describe a case of MIDD with acute mitochondrial decompensation that progressed to MELAS.Results: A 63-year-old male with MIDD and a history of hypoglycemic seizures presented for evaluation of altered mental status with fever, tachycardia, hypotension, and somnolence. His history was also significant for deafness and cochlear implants. The physical exam results were consistent with mild, proximal muscle wasting. The initial workup was concerning for sepsis and a urinary tract infection. Laboratory evaluation revealed lactic acidosis with normal white cell count, liver enzymes, and ammonia level. After fluid resuscitation and 4 days of broad-spectrum antibiotics, his mental status improved. Then he became obtunded again, and a stroke alert was called. Stroke workup results, including imaging studies, were negative, ammonia level was high, and he developed transaminitis. There was a concern for carnitine deficiency given the underlying mitochondrial disease, valproic acid use, and sepsis. He stabilized for a few days but then developed focal left-arm paresis. Stroke workup again was negative and diagnosis of MELAS was considered. Arginine supplementation was initiated with improvement of the focal weakness. He was discharged to rehabilitation.Conclusion: This case highlights that MIDD and MELAS are a spectrum of the same disease process, and emphasizes the importance of recognizing MELAS as a rare presentation in MIDD patients irrespective of age. (AACE Clinical Case Rep. 2018;4:e228-e231) Abbreviations: MELAS = mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes; MIDD = maternally inherited diabetes and deafness

Clinical Approaches for Mitochondrial Diseases

“…There remains a question regarding the different consequences of MELAS and MIDD despite being associated with the same mutation. Previous case studies have shown that MIDD patients are likely to exhibit a low heteroplasmy of mutated DNA [120][121][122]; however, apart from this finding, no other direct evidence has been found to provide a clear explanation.…”

Refractory Hypotension in a Late-Onset Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS) Male with m.3243 A>G Mutation: A Case Report

“…To the best of our knowledge, hypotension attributed to a component of autonomic dysfunction in MELAS patients was first reported by Zelnik et al [15]. Subsequently, hypotension was occasionally reported, with these case studies providing more specific underlying causes for hypotension (for example, hypothyroidism [32] and sepsis [33]), and the blood pressure abnormalities or variations were not discussed in-depth. On the contrary, adult MELAS patients have been reported with elevated rates of hypertension [34].…”