Late-onset MELAS syndrome with mtDNA 14453G→A mutation masquerading as an acute encephalitis: a case report

Abstract

Background: A unique patient with MELAS syndrome, who initially masqueraded as having acute encephalitis and was eventually diagnosed with MELAS syndrome harboring a mtDNA 14453G → A mutation, is described. Case presentation: A 74-year-old Japanese man was admitted to another hospital due to acute onset of cognitive impairment and psychosis. After 7 days he was transferred to our hospital with seizures and deteriorating psychosis. The results of primary ancillary tests that included EEG, CSF findings, and brain MRI supported the diagnosis of an acute encephalitis. HSV-DNA and antibodies against neuronal surface antigens in the CSF were all negative. With the assistance of the lactate peak on the brain lesions in the magnetic resonance spectroscopy image and genetic analysis of the biopsied muscle, he was eventually diagnosed with MELAS syndrome harboring mtDNA 14453G → A mutation in the ND6 gene. Conclusions: This case provides a caveat that MELAS syndrome can manifest in the symptoms and ancillary tests masquerading as an acute encephalitis caused by infection or autoimmunity. This is the first adult patient seen to harbor the mtDNA14453G → A with a unique onset, which broadens the phenotypic spectrum of MELAS syndrome associated with ND6 gene mutation.

Rare Phenotypic Manifestations of MELAS

“…Rare non-specific manifestations include developmental delay or fever (<10% of cases). 4 5 Non-specific manifestations of MELAS may also include dysmorphism (hypertelorism, protruding ears). 6 Knowing the entire spectrum of the phenotype is crucial, as prospective investigations may also be carried out for these rare features and some of them may strongly determine the prognosis and outcome.…”

Adult-Onset Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-Like Episodes (MELAS) in a Patient Without Significant Family History

“…These cases show wide variability in clinical presentation. In a report similar to ours, Yokota et al documented a 73-year-old man with no known relevant family history presenting with a stroke-like episode characterized by altered mental status and an afebrile seizure that was initially attributed to herpes simplex virus (HSV) encephalitis [ 3 ]. As our patient, after DWI imaging showed lesions in the occipital areas and elevated lactate in the CSF, a diagnosis of MELAS was considered and confirmed with genetic testing [ 4 ].…”

“…Several recent case reports have documented patients with no family history of MELAS that were diagnosed after the age of 50 [3][4][5][6]. These cases show wide variability in clinical presentation.…”

Monogenic Causes of Strokes

“…There are two groups of mutations in mtDNA—one type of mutation affects general mitochondrial protein biosynthesis (tRNA and rRNA genes), exemplified by the 3243A→G nucleotide mutation in the mitochondrial tRNALeu gene; the other type of mutation causes amino acid substitutions in enzyme complexes involved in OXPHOS (protein coding genes). Dysfunction of respiratory complex I (NADH dehydrogenase type I: ND), which plays an important role in OXPHOS complexes, is considered one of the main mechanisms underlying mitochondrial diseases, which include MELAS [ 26 , 27 , 28 ]. The literature highlights the genetic heterogeneity of MELAS syndrome [ 29 ].…”

“…Other genes whose mutations lead to MELAS include MTTQ, MTTH, MTTK, MTTS1, MTND1, MTND5, MTND6 and MTTS2. Case reports with different mutations are presented in the literature, e.g., a base and amino acid exchange mutation in the MT-ND4 gene (m.12015T>C on p.Leu419Pro) and the 14453G→A mutation with associated mutations in the D-loop regions of mitochondrial DNA [ 26 , 33 ].…”