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Vitiligo Vulgaris
Published in Vineet Relhan, Vijay Kumar Garg, Sneha Ghunawat, Khushbu Mahajan, Comprehensive Textbook on Vitiligo, 2020
A rare progressive neurodegenerative disorder, mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke (MELAS) syndrome, presents with central nervous system abnormalities, neurosensory hearing loss, diabetes mellitus, and cardiomyopathy. One study found vitiligo in 11% (3/28) of MELAS patients [34].
Mitochondrial encephalomyelopathy, lactic acidosis, and stroke-like episodes (MELAS)
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
The MELAS syndrome is the result of mutation in mitochondrial genes for tRNA [41]. The most common is A-to-G transition at position 3243 of the tRNALeu(UUR) (see Figure 51.1) [4, 5]. Approximately 80 percent of affected individuals have this mutation in the dihydrouridine loop of the gene [8, 16, 42–44]. The other common mutation, occurring in about 8.5 percent of individuals, is also in the tRNALeu(UUR) at 3271 in the anticodon, where there is a T-to-C transversion [7]. The G-to-A transversion at 3252 of the same gene has been reported in mitochondrial encephalopathy [45]. Another mutation in the dihydrouridine loop at nucleotide 3250 is a T-to-C transition [42]. Another mutation in this gene is an A-to-T change at position 3256 [46]. A 5814G in the tRNACys gene was reported in a patient with cardiomyopathy and myopathy [35].
Cardiac Hypertrophy, Heart Failure and Cardiomyopathy
Published in Mary N. Sheppard, Practical Cardiovascular Pathology, 2022
Other DCM associated with defects in the mitochondrial respiratory and oxidative systems due to mutations in mitochondrial DNA are maternally transmitted. Most mitochondrial genetic defects predominantly affect skeletal muscle, but the conduction system of the heart is also very susceptible. In the Kearns–Sayre syndrome, ocular paralysis is associated with progressive loss of conduction tissue leading to heart block without any myocardial contraction loss. The phenotypic expression of mitochondrial cardiac disease is very wide-ranging, from purely conduction tissue loss to a conventional DCM to an HCM. While, in the mitochondrial myopathies, the mitochondria under electron microscopy may appear large and abnormal, the ease with which fixation artefacts can distort the structure means that cardiac biopsy to confirm or exclude the diagnosis of a mitochondrial abnormality is not reliable. The pattern of inheritance down the female line provides the clue to proceed to formal genetic analysis of mitochondrial DNA. The heart primarily relies on the energy produced through aerobic respiration and is one of the organs that is most affected by mitochondrial disease. In general, myocardial hypertrophy is observed to accompany a diminished left ventricular function, cardiac arrhythmias and HF in patients with these conditions. The severity is directly linked to the mutation load. In addition, cardiotoxic drugs, such as anticancer drugs, can damage the myocardial mitochondria by altering matrix metalloproteases by enhancing the production of ROS, which induces apoptosis. Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome is caused by the most common mitochondrial 3243 A→G mutation.
Laboratory testing for mitochondrial diseases: biomarkers for diagnosis and follow-up
Published in Critical Reviews in Clinical Laboratory Sciences, 2023
Abraham J. Paredes-Fuentes, Clara Oliva, Roser Urreizti, Delia Yubero, Rafael Artuch
The current “omics” techniques such as genomics, metabolomics, lipidomics, transcriptomics, and proteomics focus on revealing and deciphering disease biochemical signatures as a comprehensive approach for identifying mitochondrial dysfunction [22]. For example, metabolomic analyses of blood samples of patients with primary and secondary MDs demonstrated disease-specific fingerprints with potential treatment targets, biomarkers, and pathogenic pathways [121]. Sharma et al. conducted proteomic and metabolomic studies on plasma samples from MELAS syndrome patients and validated a panel of 20 monitoring biomarkers. This biosignature included traditionally used biomarkers, more recently identified biomarkers (such as GDF-15), and a set of new analytes that had not been previously linked to mitochondrial dysfunction (Table 1) [122].
Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes syndrome: a case report
Published in Ultrastructural Pathology, 2023
Yong-Xin Ru, Li Ying, Shu-Xu Dong, Hui-Ming Yi, Liu Jing, Zhang Yongqiang
MELAS syndrome is a group of heterogeneous disorders resulting from mutations in mitochondrial DNA (mtDNA).4–6 The most common mutation is m.3243ANG in the MT-TL1 gene encoding mitochondrial tRNALeu (UUR), which leads to shortage of mitochondrial energy production. The deficiency stimulates mitochondrial proliferation in smooth muscle and endothelial cells, leading to angiopathy and microvascular impediment in multiple organs.7 Mitochondrial malfunction is widely associated with various problems ranging from lethal encephalopathies and neurodegenerative conditions to amyotrophic disorders. Ragged-red fibers (RRFs) as revealed in muscle biopsy are a hallmark of MELAS syndrome, but the link between morphologic alteration and function is poorly understood as yet.8 Here, we studied the histopathologic characteristics of RRFs in gastrocnemius muscle from a patient with MELAS syndrome by light microscopy and TEM.
Ophthalmological Manifestations of Hereditary Myopathies
Published in Journal of Binocular Vision and Ocular Motility, 2022
Marta Saint-Gerons, Miguel Angel Rubio, Gemma Aznar, Ana Matheu
More than 30 pathogenic mutations for MELAS syndrome have been found but the m3243A>G mutation in the MT-TL1 gene encoding the mitochondrial tRNA(Leu(UUR)) still accounts for 78–80% of cases.28 The signs and symptoms of this disorder most often appear in childhood following a period of normal development, although they can begin at any age. Most affected individuals experience stroke-like episodes beginning before age 40. The typical clinical manifestations of MELAS include stroke-like episodes (84–99%),39 seizures (≥25%), short stature (50–74%), muscle weakness (7–89%), headache (≥25%), hearing loss (7–89%), PEO (25–30%),24 optic atrophy (20%), pigmentary retinopathy (16%), and maculopathies.23,40 Repeated stroke-like episodes can progressively damage the brain, leading to dementia (40–90%).39,40 Occipital and temporal cortical regions are primarily affected leading to hemianopia or hemi-paresis.41 Biochemical and histopathological features encompass the presence of elevated lactate in serum and cerebrospinal fluid, ragged-red fibers in muscle biopsy (80–100%), and strongly succinate dehydrogenase (SDH)- positive blood vessels.42