Mitochondrial disorders may present at any age. [ncbi.nlm.nih.gov]

“AIFM1 mutation presenting with fatal encephalomyopathy and mitochondrial disease in an infant.” [dash.harvard.edu]

The abnormal muscle and mitochondrial morphology in a variety of clinical presentations from isolated ophthalmoplegia to severe encephalopathy are also elaborated. [books.google.de]

It has a wide range of clinical presentations, from lethal infantile mitochondrial disease to isolated myopathy. 1– 3 Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is one of the syndromes associated with complex I deficiency [jmg.bmj.com]

• Epilepsy

  […] clinical features that fall into a discrete clinical syndrome, such as the Kearns-Sayre syndrome (KSS), chronic progressive external ophthalmoplegia (CPEO), mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), myoclonic epilepsy [ncbi.nlm.nih.gov]

  […] and Ragged Red Muscle Fibers MERRF/MELAS overlap disease Myoclonic Epilepsy and Psychomotor Regression Progressive Encephalopathy Epilepsy, Strokes, Optic atrophy, & Cognitive decline Leigh Disease (Maternally Inherited Leigh Syndrome) Kearns-Sayre Syndrome [meduniwien.ac.at]

  […] reported as Leigh Disease FICP Fatal Infantile Cardiomyopathy Plus, a MELAS-associated cardiomyopathy MELAS Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes LDYT Leber's hereditary optic neuropathy and DYsTonia MERRF Myoclonic Epilepsy [mitomap.org]

  36 Case 6 - Myoclonic Epilepsy with Ragged Red Fibers (MERRF) Clinical Features: Starts in 20’s to 30’s Proximal muscle weakness Epilepsy with Myoclonus Dementia Ataxia Cardiomyopathy Also get pyramidal tract signs, neuropathy, optic nerve atrophy, and [slideplayer.com]

• Weakness

  […] syndrome, such as the Kearns-Sayre syndrome (KSS), chronic progressive external ophthalmoplegia (CPEO), mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), myoclonic epilepsy with ragged-red fibers (MERRF), neurogenic weakness [ncbi.nlm.nih.gov]

  Symptoms: Myoclonus, epilepsy, progressive ataxia, muscle weakness and degeneration, deafness, and dementia. [umdf.org]

• Falling

  Many individuals with a mutation of mtDNA display a cluster of clinical features that fall into a discrete clinical syndrome, such as the Kearns-Sayre syndrome (KSS), chronic progressive external ophthalmoplegia (CPEO), mitochondrial encephalomyopathy [ncbi.nlm.nih.gov]

  21 Case 2 – Leigh’s Disease 14 year old girl CC: New onset seizures HPI: Normal up until 2 months prior to presentation when she started having falls. She then had several seizures, when her parents brought her to the hospital. [slideplayer.com]

  Their emotions rise and falls may destroy them morally. They can arrange anything in their life as long as it filled the hearts. LEVIM (letter M) They distributes energy which they receives from the universe very well. [acronym24.com]

  […] features of the stroke-like episodes themselves which are the cardinal features of the MELAS phenotype. 21 22 The additional features represented in the acronym are variably present and there may be other features of respiratory chain disease which fall [jnnp.bmj.com]

• Anemia

  At 7 weeks of age, red blood cells were transfused due to the rapidly progressive anemia ( Supplementary Table 2 ). At 2 months of age, he showed axial hypotonia. [doi.org]

  Biochemical and Biophysical Research Communications 177(1): 518-525, 1991 Mitochondrial myopathy with anemia, cardiomyopathy, and lactic acidosis: a distinct late onset mitochondrial disorder. American Journal of Medical Genetics 51(2): 114-120, 1994 [eurekamag.com]

  Pathologies are abbreviated as follows: A, ataxia; ADPD, Alzeimer's disease and Parkinsons disease ; AISA, acquired idiopathic sideroblastic anemia; AMDF, ataxia, mental deterioration, deafness; CD, Cox deficiency; CIPO, chronic instestinal pseudoobstruction [europeanmedical.info]

  Defects in nuclear-encoded mitochondrial genes are associated with hundreds of clinical disease phenotypes including anemia, dementia, hypertension, lymphoma, retinopathy, seizures, and neurodevelopmental disorders. [10] A study by Yale University researchers [en.wikipedia.org]

  […] and endocrine dysfunction Laboratory: Increased CSF protein and lactate MRI- bilateral subcortical white matter T2 hyperintensities involving basal ganglia, thalamus, and brainstem Pathology: ragged red fibers Note: Pearson’s syndrome- sideroblastic anemia [slideplayer.com]

• Asymptomatic

  […] increased frequency. 3 question in 14 years 37 Cases 7, 8, and 9 3 month old girl Recurrent episodes of hypoglycemia, hypotonia, and profound acidosis 35 year old man Elevated CK and recurrent rhabdomyolysis after vigorous exercise 60 year old woman Asymptomatic [slideplayer.com]

  Her asymptomatic mother did not have the mutation. The G at np 15995 is highly conserved across species, from the sea urchin to mammals. [clinchem.aaccjnls.org]

  […] diseases causing severe progressive disability and reduced lifespan, such as Huntington's disease, familial ALS, and early onset familial Alzheimer's disease. 3 Patients need genetic counseling prior to obtaining DNA tests and this is especially true for asymptomatic [ahcmedia.com]

  At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. [umdf.org]

• Hepatomegaly

  Begins soon after birth Seizures Arrhythmias Hypoketotic hypoglycemia Hyperammoniemia Hepatomegaly Cardiomyopathy Many infants with CACT deficiency do not survive the newborn period. [slideplayer.com]

• Myopathy

  MalaCards integrated aliases for Mitochondrial Myopathy, Lethal, Infantile: Name: Mitochondrial Myopathy, Lethal, Infantile 58 74 Lethal Infantile Mitochondrial Myopathy 60 30 Myopathy, Mitochondrial, Lethal, Infantile 41 Lethal Infantile Mitochondrial [malacards.org]

  GTR MeSH Orphanet C Clinical test, R Research test, O OMIM, G GeneReviews, V ClinVar C R O G V Lethal infantile mitochondrial myopathy Follow this link to review classifications for Lethal infantile mitochondrial myopathy in Orphanet. [ncbi.nlm.nih.gov]

  (MEGF10) DISTAL MYOPATHIES Distal myopathy with decreased caveolin 3 (CAV3) Miyoshi muscular myopathy (DSYF) Miyoshi muscular myopathy 3 (ANO5) Distal myopathy, with anterior tibial onset (DSYF) Distal myopathy 1, Laing (MYH7) Tardive tibial muscular [meduniwien.ac.at]

• Hearing Impairment

  impairment and ophthalmoplegia [ 6 ]. [ijponline.biomedcentral.com]

• Blepharoptosis

  The patient developed hypotonia and blepharoptosis and exhibited growth retardation. Biochemical examination of muscle tissue revealed a partial deficiency of cytochrome c oxidase. [wwww.unboundmedicine.com]

• Encephalopathy

  Common central nervous system findings are fluctuating encephalopathy, seizures, dementia, migraine, stroke-like episodes, ataxia, and spasticity. [ncbi.nlm.nih.gov]

  Autopsy, at the age of 4 mo, revealed features of mitochondrial encephalopathy, myopathy, and involvement of peripheral nerves with axonal degeneration. [dash.harvard.edu]

  The abnormal muscle and mitochondrial morphology in a variety of clinical presentations from isolated ophthalmoplegia to severe encephalopathy are also elaborated. [books.google.de]

  27 Mitochondrial Encephalopathy Lactic Acidosis and Stroke-Like Episodes (MELAS) Clinical features- Myopathy Encephalopathy with headaches and vomiting Stroke like symptoms: hemiparesis, hemianopsia most common Short stature, hearing loss, lactic acidosis [slideplayer.com]

• Seizure

  Common central nervous system findings are fluctuating encephalopathy, seizures, dementia, migraine, stroke-like episodes, ataxia, and spasticity. [ncbi.nlm.nih.gov]

  Symptoms: general: mental retardation, seizures, speech delay. [umdf.org]

  There followed progressive cognitive decline, cerebellar ataxia, and complex partial seizures. [jnnp.bmj.com]

  21 Case 2 – Leigh’s Disease 14 year old girl CC: New onset seizures HPI: Normal up until 2 months prior to presentation when she started having falls. She then had several seizures, when her parents brought her to the hospital. [slideplayer.com]

• Ataxia

  Common central nervous system findings are fluctuating encephalopathy, seizures, dementia, migraine, stroke-like episodes, ataxia, and spasticity. [ncbi.nlm.nih.gov]

  Ataxia Telangiectasia Friedreich Ataxia Spinocerebellar Ataxia Type 1 Spinocerebellar Ataxia Type II Spinocerebellar Ataxia Type III Spinocerebellar Ataxia Type VI Spinocerebellar Ataxia Type VII Ataxia Telangiectasia ATM 11q22-q23 Autosomal Recessive [ahcmedia.com]

  Spinocerebellar ataxia 2 (ATXN2) Spinocerebellar ataxia 3 (ATXN3) Spinocerebellar ataxia 6 (CACNA1A) Spinocerebellar ataxia 7 (ATXN7) HEREDITARY CARDIOMYOPATHIES Cardiomyopathy, familial hypertrophic (CAV3) Dilated cardiomyopathy, 1I (DES) Cardiomyopathy [meduniwien.ac.at]

  Symptoms: Myoclonus, epilepsy, progressive ataxia, muscle weakness and degeneration, deafness, and dementia. [umdf.org]

• Stroke

  Common central nervous system findings are fluctuating encephalopathy, seizures, dementia, migraine, stroke-like episodes, ataxia, and spasticity. [ncbi.nlm.nih.gov]

  Two of the patients—1 and 5—only had single events and were followed up for 7 and 8 years after the initial stroke respectively with no further events. Patients 4 and 5 illustrate that the stroke-like episodes can be many years apart. [jnnp.bmj.com]

  It has a wide range of clinical presentations, from lethal infantile mitochondrial disease to isolated myopathy. 1– 3 Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is one of the syndromes associated with complex I deficiency [jmg.bmj.com]

  Congenital Myasthenic Syndromes Spinal Muscular Atrophies & Motor Neuron Diseases Hereditary Ataxias Hereditary Cardiomyopathies Hereditary Motor and Sensory Neuropathies Neurodegenerative Lysosomal Storage Diseases Disorders of Neuronal Migration Hereditary Stroke [meduniwien.ac.at]

• Chronic Progressive External Ophthalmoplegia

  Many individuals with a mutation of mtDNA display a cluster of clinical features that fall into a discrete clinical syndrome, such as the Kearns-Sayre syndrome (KSS), chronic progressive external ophthalmoplegia (CPEO), mitochondrial encephalomyopathy [ncbi.nlm.nih.gov]

  Progressive External Ophthalmoplegia KSS Kearns Sayre Syndrome DM Diabetes Mellitus DMDF Diabetes Mellitus + DeaFness CIPO Chronic Intestinal Pseudoobstruction with myopathy and Ophthalmoplegia DEAF Maternally inherited DEAFness or aminoglycoside-induced [mitomap.org]

  Links: OMIM Long Name: ATP synthase deficiency Symptoms: Slow, progressive myopathy. Links: OMIM Long Name: Chronic Progressive External Ophthalmoplegia Syndrome. [umdf.org]

  external ophthalmoplegia, with mtDNA deletions, autosomal dominant 1 (POLG) Progressive external ophthalmoplegia, with mtDNA deletions, autosomal recessive (POLG) Alpers syndrome (POLG) Encephalopathy (POLG) Leigh Syndrome (NDUFAF2, NDUFA10) Mitochondrial [meduniwien.ac.at]

Treatment: Diet supplementation with L-Carnitine. [specialneedshomeschooling.com]

After treatment, metabolic acidosis and hypercalciuria improved, and the patient had a catch-up growth phase. [wwww.unboundmedicine.com]

MYTH Since mitochondrial diseases are incurable, no treatments can be given to these patients. FACT Even though these disorders are long term and incurable, treatments are available. [my.clevelandclinic.org]

[…] expression of mitochondrial proteins as a radical treatment for mtDNA mutation load. [en.wikipedia.org]

Treatment response appeared more favorable in younger patients.* 1 question in 14 years * Mercimek-Mahmutoglu S, Stoeckler-Ipsiroglu S, Adami A, et al. GAMT deficiency: features, treatment, and outcome in an inborn error of creatine synthesis. [slideplayer.com]

The prognosis for MELAS is poor. Typically, the age of death is between 10 to 35 years, although some patients may live longer. [umdf.org]

The prognosis for MERRF varies widely depending on age of onset, type and severity of symptoms, organs involved, and other factors. Sources: Dr. Rolf Luft; The development of mitochondrial medicine. [specialneedshomeschooling.com]

[…] demyelination Genetics Mutations in either mtDNA or nuclear DNA Pyruvate dehydrogenase (PDHC) most common Imaging/Pathology Bilateral, symmetric necrotizing lesions with spongy changes, microcysts in the basal ganglia, thalamus, brainstem, and spinal cord Prognosis [slideplayer.com]

The prognosis is severe [ 27 ]. i) DGUOK The deoxyguanosine kinase ( DGUOK ) gene lies on chromosome 2p13, and codes for a 2-deoxyribonucleoside enzyme that catalyzes the first step in the mitochondrial deoxypurine salvage pathway. [ijponline.biomedcentral.com]

[…] acidosis 33 HP:0003128 14 lethal infantile mitochondrial myopathy 33 HP:0009069 Symptoms via clinical synopsis from OMIM: 58 Metabolic Features: lactic acidosis Laboratory Abnormalities: mutant mtdna threonine transfer rna gene (mttt, ) of questionable etiology [malacards.org]

Table 1 summarizes the main clinical manifestations and molecular etiologies associated with these different forms. [ijponline.biomedcentral.com]

Most of the patients had unknown disease etiologies with unexplained multisystemic problems and defective energy metabolism without defined diagnosis. [clinchem.aaccjnls.org]

Mitochondrial Myopathy, Lethal, Infantile: Name: Mitochondrial Myopathy, Lethal, Infantile 58 74 Lethal Infantile Mitochondrial Myopathy 60 30 Myopathy, Mitochondrial, Lethal, Infantile 41 Lethal Infantile Mitochondrial Disease 60 Characteristics: Orphanet epidemiological [malacards.org]

Epidemiology [ edit ] About 1 in 4,000 children in the United States will develop mitochondrial disease by the age of 10 years. [en.wikipedia.org]

The incidence is unknown, although the epidemiological studies of the MELAS-3243 mtDNA mutation have estimated the prevalence to be 1-16/100,000 in the adult population. There is no cure or specific treatment for MELAS. [umdf.org]

PubMed Central View Article PubMed Google Scholar Schaefer AM, Taylor RW, Turnbull DM, Chinnery PF: The epidemiology of mitochondrial disorders- past, present and future. Biochim Biophys Acta. 2004, 1659 (Suppl 2–3): 115-120. [ijponline.biomedcentral.com]

"Mitochondrial modulators for bipolar disorder: A pathophysiologically informed paradigm for new drug development". Australian & New Zealand Journal of Psychiatry. 47 (1): 26–42. doi : 10.1177/0004867412449303. [en.wikipedia.org]

"Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease". Nature. 465 (7294): 82–85. doi : 10.1038/nature08958. PMC 2875160. PMID 20393463. ^ "UK urged to permit IVF procedure to prevent fatal genetic diseases". [en.wikipedia.org]

Propofol infusion syndrome More common in children than adults metabolic acidosis, heart failure, renal failure, hyperkalemia and rhabdo Prevent by giving carbohydrate load/infusion (children have limited carbohydrate reserves) Treat by hemofiltration [slideplayer.com]

Maternal inheritance of mouse mtDNA in interspecific hybrids: segregation of the leaked paternal mtDNA followed by the prevention of subsequent paternal leakage. Genetics 1998;148:851–7. Schwartz, M. & Vissing, J. [slideshare.net]

View Article PubMed Google Scholar Parini R, Furlan F, Notarangelo L, Spinazzola A, Uziel G, Strisciuglio P, Concolino D, Corbetta C, Nebbia G, Menni F, Rossi G, Maggioni M, Zeviani M: Glucose metabolism and diet-based prevention of liver dysfunction [ijponline.biomedcentral.com]