MELAS and Kearns–Sayre overlap syndrome due to the mtDNA m. A3243G mutation and large-scale mtDNA deletions

Abstract

This paper reported an unusual manifestation of a 19-year-old Chinese male patient presented with a complex phenotype of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome and Kearns–Sayre syndrome (KSS). He was admitted to our hospital with the chief complaint of “acute fever, headache and slow reaction for 21 days”. He was initially misdiagnosed as “viral encephalitis”. This Chinese man with significant past medical history of intolerating fatigue presented paroxysmal neurobehavioral attacks that started about 10 years ago. During this span, 3 or 4 attack clusters were described during which several attacks occurred over a few days. The further examination found that the hallmark signs of this patient included progressive myoclonus epilepsy, cerebellar ataxia, hearing loss, myopathic weakness, ophthalmoparesis, pigmentary retinopathy and bifascicular heart block (Wolff–Parkinson–White syndrome). By young age the disease progression is characterized by the addition of migraine, vomiting, and stroke-like episodes, symptoms of MELAS expression, which indicated completion of the MELAS/KSS overlap syndrome. The m. A3243G mitochondrial DNA mutation and single large-scale mtDNA deletions were found in this patient. This mutation has been reported with MELAS, KSS, myopathy, deafness and mental disorder with cognitive impairment. This is the first description with a MELAS/KSS syndrome in Chinese.

Stroke-like Episodes in Inherited Neurometabolic Disorders

“…Leukoencephalopathy in KSS was also demonstrated by MRI to show cerebral, cerebellar and brainstem atrophy. T2 signals include subcortical prolongation with subcortical calcifications, with or without bilateral basal ganglia calcific deposits [ 39 , 40 , 41 , 42 ].…”

“…The features of various neurometabolic disorders characterized by the occurrence of SLEs include genetic and molecular basis, clinical manifestations, MRI and EEG results, onset and prevalence and treatment methods ( Table 1 ) [ 2 , 3 , 4 , 7 , 8 , 9 , 11 , 13 , 14 , 15 , 16 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , …”

Mutational Analysis of Mitochondrial tRNA Genes in 200 Patients with Type 2 Diabetes Mellitus

“… 42 This mutation also led to mitochondrial encephalomyopathy, lactic acidosis and stroke-like symptoms (MELAS). 43 Molecular analysis revealed that this mutation reduced the steady-state level, aminoacylation, as well as codon recognition of tRNA Leu(UUR) . 44 As a result, the A3243G mutation caused the pre-termination of transcription and expression impeding of normal rRNA, thus compromising mitochondrial protein synthesis, ATP synthesis and organic metabolism.…”

Kearns Sayre Syndrome: A Mitochondrial Disorder

“…Additionally, because a variety of genetic mutations deleteriously affect mitochondrial function it can be very daunting to make a comprehensive diagnosis (Gorman et al, 2015). The clinical presentations of mitochondrial disorders have common overlaps between Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like episodes syndrome (MELAS) and KSS (Yu, et al, 2016). Mitochondrial encephalomyopathy is defined by disease, damage, or malfunction of the brain indicating that KSS patients have a severely affected central nervous system (CNS) (Quijada-Fraile et al, 2014).…”