Presentation
Mitochondrial disorders may present at any age. [ncbi.nlm.nih.gov]
The abnormal muscle and mitochondrial morphology in a variety of clinical presentations from isolated ophthalmoplegia to severe encephalopathy are also elaborated. [books.google.de]
“AIFM1 mutation presenting with fatal encephalomyopathy and mitochondrial disease in an infant.” [dash.harvard.edu]
Entire Body System
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Death in Infancy
The MDSs are rare, devastating diseases that manifest typically, although not exclusively, soon after birth, and usually lead to death in infancy or early childhood. [ijponline.biomedcentral.com]
Respiratoric
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Respiratory Distress
distress 60 33 occasional (7.5%) Occasional (29-5%) HP:0002643 8 areflexia 60 33 occasional (7.5%) Occasional (29-5%) HP:0001284 9 lethargy 60 33 occasional (7.5%) Occasional (29-5%) HP:0001254 10 generalized neonatal hypotonia 60 33 occasional (7.5% [malacards.org]
distress and dysphagia (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) [meduniwien.ac.at]
Cardiovascular
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Tachycardia
Click Here to download this mito profile (PDF) Links: NINDS OMIM, X-linked: OMIM, Adult-onset: OMIM Symptoms: Hypermetabolism, with fever, heat intolerance, profuse perspiration, polyphagia, polydipsia, ragged-red fibers, and resting tachycardia. [umdf.org]
Click Here to download this mito profile (PDF) Links: NINDS OMIM, X-linked: OMIM, Adult-onset: OMIM Luft Disease Symptoms: Hypermetabolism, with fever, heat intolerance, profuse perspiration, polyphagia, polydipsia, ragged-red fibers, and resting tachycardia [specialneedshomeschooling.com]
Eyes
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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]
Neurologic
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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: Chronic Progressive External Ophthalmoplegia Syndrome. Symptoms: Similar to those of KSS plus: visual myopathy, retinitis pigmentosa, dysfunction of the central nervous system. Cause: Single mitochondrial DNA deletions. [umdf.org]
Progressive External Ophthalmoplegia Maternal Myopathy and Cardiomyopathy Maternally Inherited Hypertrophic Cardiomyopathy Maternally Inherited Cardiomyopathy Fatal Infantile Cardiomyopathy Plus, a MELAS-associated cardiomyopathy Mitochondrial Encephalocardiomyopathy [meduniwien.ac.at]
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Neonatal Hypotonia
hypotonia 60 33 occasional (7.5%) Occasional (29-5%) HP:0008935 11 fatal liver failure in infancy 60 33 occasional (7.5%) Occasional (29-5%) HP:0006583 12 myopathy 33 HP:0003198 13 lactic acidosis 33 HP:0003128 14 lethal infantile mitochondrial myopathy [malacards.org]
Mutations in RRM2B usually result in neonatal hypotonia, lactic acidosis, failure to thrive and tubulopathy. Psychomotor delay, sensorineural hearing loss and a profound reduction of mtDNA copy numbers in skeletal muscle [ 18 ] are also present. [ijponline.biomedcentral.com]
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Areflexia
Frequent (79-30%) HP:0000590 5 severe lactic acidosis 60 33 frequent (33%) Frequent (79-30%) HP:0004900 6 seizures 60 33 occasional (7.5%) Occasional (29-5%) HP:0001250 7 neonatal respiratory distress 60 33 occasional (7.5%) Occasional (29-5%) HP:0002643 8 areflexia [malacards.org]
[…] recessive (BIN1) Central core disease of muscle (RYR1) Myopathy, congenital, with fiber-type disproportion (ACTA1, SEPN1, TPM3) Minicore myopathy, severe classic form (SEPN1) Early-onset myopathy with fatal cardiomyopathy (TTN) Early-onset myopathy, areflexia [meduniwien.ac.at]
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Paresthesia
The neuropathy typically presents with distal weakness and paresthesias, showing a symmetric stocking-glove distribution. Ptosis and ophthalmoplegia are common. Affected individuals can have elevated CSF protein and plasma lactate. [ijponline.biomedcentral.com]
Treatment
The final section exclusively addresses the management of cardiovascular genetic disorders, specifically considering stem cell therapy, genetic counseling, pharmacogenomics and the social and ethical issues surrounding disease treatment. [books.google.com]
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]
Prognosis
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]
Etiology
[…] 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]
Epidemiology
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]
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]
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]
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]
Pathophysiology
"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. PMID 22711881. [en.wikipedia.org]
Prevention
"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]