Mitochondrial myopathy, encephalomyopathy, lactic acidosis, and stroke-like episodes
Basal ganglia calcification, cerebellar atrophy, increased lactate; a CT image of a person diagnosed with MELAS
Specialty
Neurology
Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is one of the family of mitochondrial cytopathies, which also include MERRF, and Leber's hereditary optic neuropathy. It was first characterized under this name in 1984.[1] A feature of these diseases is that they are caused by defects in the mitochondrial genome which is inherited purely from the female parent.[2]
Contents
1Signs and symptoms
2Genetics
2.1NADH dehydrogenase
2.2Transfer RNAs
2.3Inheritance
3Diagnosis
4Treatment/prognosis
5Epidemiology
6References
7See also
7.1Internal links
7.2External links
Signs and symptoms
MELAS is a condition that affects many of the body's systems, particularly the brain and nervous system (encephalo-) and muscles (myopathy). In most cases, the signs and symptoms of this disorder appear in childhood following a period of normal development.[3] Early symptoms may include muscle weakness and pain, recurrent headaches, loss of appetite, vomiting, and seizures. Most affected individuals experience stroke-like episodes beginning before age 40. These episodes often involve temporary muscle weakness on one side of the body (hemiparesis), altered consciousness, vision abnormalities, seizures, and severe headaches resembling migraines. Repeated stroke-like episodes can progressively damage the brain, leading to vision loss, problems with movement, and a loss of intellectual function (dementia). The stroke-like episodes can be mis-diagnosed as epilepsy by a doctor not aware of the MELAS condition.
Most people with MELAS have a buildup of lactic acid in their bodies, a condition called lactic acidosis. Increased acidity in the blood can lead to vomiting, abdominal pain, extreme tiredness (fatigue), muscle weakness, loss of bowel control, and difficulty breathing. Less commonly, people with MELAS may experience involuntary muscle spasms (myoclonus), impaired muscle coordination (ataxia), hearing loss, heart and kidney problems, diabetes, epilepsy, and hormonal imbalances.
The presentation of some cases is similar to that of Kearns-Sayre syndrome.[4]
Genetics
Muscle biopsy of a person diagnosed with MELAS but carrying no known mutation. (a) Modified Gomori trichrome stain showing several ragged red fibers (arrowhead). (b) Cytochrome c oxidase stain showing Type-1 lightly stained and Type II fibers, darker fibers, and a few fibers with abnormal collections of mitochondria (arrowhead). Note cytochrome c oxidase negative fibers as usually seen in mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS). (c) Succinate dehydrogenase staining showing a few ragged blue fibers and intense staining in the mitochondria of the blood vessels (arrow). (d) Electron microscopy showing abnormal collection of mitochondria with paracrystalline inclusions (arrowhead), osmiophilic inclusions (large arrowhead) and mitochondrial vacuoles (small arrowhead).[5]
MELAS is caused by mutations in the genes in mitochondrial DNA.
NADH dehydrogenase
Some of the genes (MT-ND1, MT-ND5) affected in MELAS encode proteins that are part of NADH dehydrogenase (also called complex I) in mitochondria, that helps convert oxygen and simple sugars to energy.[6]
Transfer RNAs
Other genes (MT-TH, MT-TL1, and MT-TV) encode mitochondrial specific transfer RNAs (tRNAs).
Mutations in MT-TL1 cause more than 80 percent of all cases of MELAS. They impair the ability of mitochondria to make proteins, use oxygen, and produce energy. Researchers have not determined how changes in mitochondrial DNA lead to the specific signs and symptoms of MELAS. They continue to investigate the effects of mitochondrial gene mutations in different tissues, particularly in the brain.
Inheritance
This condition is inherited in a mitochondrial pattern, which is also known as maternal inheritance and heteroplasmy. This pattern of inheritance applies to genes contained in mitochondrial DNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, only females pass mitochondrial conditions to their children. Mitochondrial disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass mitochondrial traits to their children. In most cases, people with MELAS inherit an altered mitochondrial gene from their mother. Less commonly, the disorder results from a new mutation in a mitochondrial gene and occurs in people with no family history of MELAS.
Diagnosis
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Treatment/prognosis
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Patients are managed according to what areas of the body are affected at a particular time. Enzymes, amino acids, antioxidants and vitamins have been used.
Also the following supplements may help:
CoQ10 has been helpful for some MELAS patients.[7] Nicotinamide has been used because complex l accepts electrons from NADH and ultimately transfers electrons to CoQ10.
Riboflavin has been reported to improve the function of a patient with complex l deficiency and the 3250T-C mutation.[8]
The administration of L-arginine during the acute and interictal periods may represent a potential new therapy for this syndrome to reduce brain damage due to impairment of vasodilation in intracerebral arteries due to nitric oxide depletion.[9][10]
Epidemiology
The exact incidence of MELAS is unknown.[11] It is one of the more common conditions in a group known as mitochondrial diseases.[11] Together, mitochondrial diseases occur in about 1 in 4,000 people.[11]
References
^Pavlakis SG, Phillips PC, DiMauro S, De Vivo DC, Rowland LP (1984). "Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes: a distinctive clinical syndrome". Ann Neurol. 16 (4): 481–8. doi:10.1002/ana.410160409. PMID 6093682.
^Hirano M, Pavlakis SG (1994). "Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS): current concepts". J Child Neurol. 9 (1): 4–13. doi:10.1177/088307389400900102. PMID 8151079.
^MELAS syndrome at NLM Genetics Home Reference
^Hirano M, Ricci E, Koenigsberger MR, Defendini R, Pavlakis SG, DeVivo DC, DiMauro S, Rowland LP (1992). "Melas: an original case and clinical criteria for diagnosis". Neuromuscul Disord. 2 (2): 125–35. doi:10.1016/0960-8966(92)90045-8. PMID 1422200.
^Abu-Amero KK, Al-Dhalaan H, Bohlega S, Hellani A, Taylor RW (2009). "A patient with typical clinical features of mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) but without an obvious genetic cause: a case report". J Med Case Reports. 3: 77. doi:10.1186/1752-1947-3-77. PMC 2783076. PMID 19946553.
^Tranchant, C.; Anheim, M. (2016). "Movement disorders in mitochondrial diseases". Revue Neurologique. doi:10.1016/j.neurol.2016.07.003. ISSN 0035-3787.
^Rodriguez MC, MacDonald JR, Mahoney DJ, Parise G, Beal MF, Tarnopolsky MA (2007). "Beneficial effects of creatine, CoQ10, and lipoic acid in mitochondrial disorders". Muscle Nerve. 35 (2): 235–42. doi:10.1002/mus.20688. PMID 17080429.
^Ogle RF, Christodoulou J, Fagan E, et al. (1997). "Mitochondrial myopathy with tRNA(Leu(UUR)) mutation and complex I deficiency responsive to riboflavin". J. Pediatr. 130 (1): 138–45. doi:10.1016/S0022-3476(97)70323-8. PMID 9003864.
^Koga Y, Akita Y, Nishioka J, et al. (2007). "MELAS and L-arginine therapy". Mitochondrion. 7 (1–2): 133–9. doi:10.1016/j.mito.2006.11.006. PMID 17276739.
^Hirata K, Akita Y, Povalko N, et al. (2007). "Effect of l-arginine on synaptosomal mitochondrial function". Brain Dev. 30 (4): 238–45. doi:10.1016/j.braindev.2007.08.007. PMID 17889473.
^ abc"MELAS". Genetics Home Reference. December 2013. Retrieved 11 April 2017. This article incorporates text from this source, which is in the public domain.
See also
Internal links
Mitochondrial Myopathy
External links
Classification
D
ICD-10: G31.8
ICD-9-CM: 277.87
OMIM: 540000
MeSH: D017241
DiseasesDB: 8254
External resources
eMedicine: ped/1406
Orphanet: 550
melas at NIH/UW GeneTests
v
t
e
Mitochondrial diseases (277.87)
Carbohydrate metabolism
PCD
PDHA
Primarily nervous system
Leigh disease
LHON
NARP
Myopathies
KSS
Mitochondrial encephalomyopathy
MELAS
MERRF
PEO
No primary system
DAD
MNGIE
Pearson syndrome
Chromosomal
OPA1
Kjer's optic neuropathy
SARS2
HUPRA syndrome
TIMM8A
Mohr–Tranebjærg syndrome
see also mitochondrial proteins
v
t
e
Diseases of myoneural junction and muscle / neuromuscular disease (G70–G73, 358–359)
Neuromuscular- junction disease
autoimmune
Myasthenia gravis
Lambert–Eaton myasthenic syndrome
Neuromyotonia
Myopathy/ congenital myopathy
Muscular dystrophy (DAPC)
AD
Limb-girdle muscular dystrophy 1
Oculopharyngeal
Facioscapulohumeral
Myotonic
Distal (most)
AR
Limb-girdle muscular dystrophy 2
Congenital
Fukuyama
Ullrich
Walker–Warburg
XR
dystrophin
Becker's
Duchenne
Emery–Dreifuss
Other structural
collagen disease
Bethlem myopathy
PTP disease
X-linked MTM
adaptor protein disease
BIN1-linked centronuclear myopathy
cytoskeleton disease
Nemaline myopathy
Zaspopathy
Channelopathy
Myotonia
Myotonia congenita
Thomsen disease
Neuromyotonia/Isaacs syndrome
Paramyotonia congenita
Periodic paralysis
Hypokalemic
Thyrotoxic
Hyperkalemic
Other
Central core disease
Mitochondrial myopathy
MELAS
MERRF
KSS
PEO
Other
Inflammatory myopathy
UpToDate Contents
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Phenotypic Analysis of Epilepsy in the Mitochondrial Encephalomyopathy, Lactic Acidosis, and Strokelike Episodes-Associated Mitochondrial DNA A3243G Mutation.
Demarest ST1, Whitehead MT1, Turnacioglu S1, Pearl PL2, Gropman AL3.
The A to G mitochondrial DNA point mutation at position 3243 (A3243G) is the most common cause of mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS), a systemic multiorgan disease. Epilepsy is a common finding but there is wide phenotypic variation that has not been th
Mutation-free baby born from a mitochondrial encephalopathy, lactic acidosis and stroke-like syndrome carrier after blastocyst trophectoderm preimplantation genetic diagnosis.
Heindryckx B1, Neupane J2, Vandewoestyne M3, Christodoulou C4, Jackers Y5, Gerris J6, Van den Abbeel E7, Van Coster R8, Deforce D9, De Sutter P10.
Mitochondrion.Mitochondrion.2014 Aug 23. pii: S1567-7249(14)00120-2. doi: 10.1016/j.mito.2014.08.005. [Epub ahead of print]
To investigate the applicability of preimplantation genetic diagnosis (PGD), we used trophectoderm (TE) biopsy to determine the mutation load in a 35-year-old female with mitochondrial encephalopathy, lactic acidosis and stroke-like syndrome (MELAS). Transfer of a mutation-free blastocyst gave birth
The ROS-sensitive microRNA-9/9* controls the expression of mitochondrial-tRNA modifying enzymes and is involved in the molecular mechanism of MELAS syndrome.
Human molecular genetics.Hum Mol Genet.2014 Aug 22. pii: ddu427. [Epub ahead of print]
Mitochondrial dysfunction activates mitochondria-to-nucleus signaling pathways whose components are mostly unknown. Identification of these components is important to understand the molecular mechanisms underlying mitochondrial diseases and to discover putative therapeutic targets. MELAS syndrome is
MELAS syndrome, a rare form of dementia, is caused by mutations in the genetic material (DNA) in the mitochondria. Melas symptoms include brain dysfunction (encephalopathy) with seizures and headaches, muscle ...
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a condition that affects many of the body's systems, particularly the brain and nervous system (encephalo-) and muscles ...
