Kearns-Sayre Syndrome
Transcomplementation between different types of respiration-deficient mitochondria with different pathogenic mutant mitochondrial DNAs. (1/60)
Two cell lines were used for determination of whether interaction occurred between different types of respiration-deficient mitochondria. One was a respiration-deficient rho- cell line having mutant mitochondrial DNA (mtDNA) with a 5,196-base pair deletion including five tRNA genes (tRNAGly, Arg, Ser(AGY), Leu(CUN), His), DeltamtDNA5196, causing Kearns-Sayre syndrome. The other was a respiration-deficient syn- cell line having mutant mtDNA with an A to G substitution at 4,269 in the tRNAIle gene, mtDNA4269, causing fatal cardiomyopathy. The occurrence of mitochondrial interaction was examined by determining whether cybrids constructed by fusion of enucleated rho- cells with syn- cells became respiration competent by exchanging their tRNAs. No cybrids were isolated in selection medium, where only respiration-competent cells could survive, suggesting that no interaction occurred, or that it occurred so slowly that sufficient recovery of mitochondrial respiratory function was not attained by the time of selection. The latter possibility was confirmed by the observations that heteroplasmic cybrids with both mutant mtDNA4269 and DeltamtDNA5196 isolated without selection showed restored mitochondrial respiration activity. This demonstration of transcomplementation between different respiration-deficient mitochondria will help in understanding the relationship between somatic mutant mtDNAs and the roles of such mutations in aging processes. (+info)Rearrangements of human mitochondrial DNA (mtDNA): new insights into the regulation of mtDNA copy number and gene expression. (2/60)
Mitochondria from patients with Kearns-Sayre syndrome harboring large-scale rearrangements of human mitochondrial DNA (mtDNA; both partial deletions and a partial duplication) were introduced into human cells lacking endogenous mtDNA. Cytoplasmic hybrids containing 100% wild-type mtDNA, 100% mtDNA with partial duplications, and 100% mtDNA with partial deletions were isolated and characterized. The cell lines with 100% deleted mtDNAs exhibited a complete impairment of respiratory chain function and oxidative phosphorylation. In contrast, there were no detectable respiratory chain or protein synthesis defects in the cell lines with 100% duplicated mtDNAs. Unexpectedly, the mass of mtDNA was identical in all cell lines, despite the fact that different lines contained mtDNAs of vastly different sizes and with different numbers of replication origins, suggesting that mtDNA copy number may be regulated by tightly controlled mitochondrial dNTP pools. In addition, quantitation of mtDNA-encoded RNAs and polypeptides in these lines provided evidence that mtDNA gene copy number affects gene expression, which, in turn, is regulated at both the post-transcriptional and translational levels. (+info)Maintenance of human rearranged mitochondrial DNAs in long-term cultured transmitochondrial cell lines. (3/60)
Large-scale rearrangements of mitochondrial DNA (mtDNA; i.e., partial duplications [dup-mtDNAs] and deletions [Delta-mtDNAs]) coexist in tissues in a subset of patients with sporadic mitochondrial disorders. In order to study the dynamic relationship among rearranged and wild-type mtDNA (wt-mtDNA) species, we created transmitochondrial cell lines harboring various proportions of wt-, Delta-, and dup-mtDNAs from two patients. After prolonged culture in nonselective media, cells that contained initially 100% dup-mtDNAs became heteroplasmic, containing both wild-type and rearranged mtDNAs, likely generated via intramolecular recombination events. However, in cells that contained initially a mixture of both wt- and Delta-mtDNAs, we did not observe any dup-mtDNAs or other new forms of rearranged mtDNAs, perhaps because the two species were physically separated and were therefore unable to recombine. The ratio of wt-mtDNA to Delta-mtDNAs remained stable in all cells examined, suggesting that there was no replicative advantage for the smaller deleted molecules. Finally, in cells containing a mixture of monomeric and dimeric forms of a specific Delta-mtDNA, we found that the mtDNA population shifted towards homoplasmic dimers, suggesting that there may be circumstances under which the cells favor molecules with multiple replication origins, independent of the size of the molecule. (+info)Focal segmental glomerulosclerosis associated with mitochondrial cytopathy. (4/60)
BACKGROUND: The nonspecific lesion of focal segmental glomerulosclerosis (FSGS) can occur as a primary disease or in a variety of secondary settings. In mitochondrial cytopathies (MCs), the phenotypic expression of the disease depends on the degree of cellular dysfunction, and this correlates with the proportion of abnormal mitochondrial DNA in the cells and the dependence of tissues on oxidative metabolism. The most common renal manifestation in MCs is tubular dysfunction; little has been reported about glomerular diseases. METHODS: Cases of four adult patients with FSGS and MC are reported. Routine histology and mitochondrial DNA analysis were carried out on renal biopsies. RESULTS: Family history and clinical manifestations in the four patients with FSGS suggested a diagnosis of MC. An A3243G transition in the mitochondrial DNA tRNA(leu(UUR)) was found in lymphocytes and kidney. Glomerular lesions of FSGS were associated with unusual hyaline lesions, which appeared to represent individual myocyte necrosis in afferent arterioles and small arteries. CONCLUSION: FSGS is a renal manifestation of MCs. The renal lesion can precede other manifestations of the genetic disease by many years. The striking arteriolar lesions in these cases may have resulted in glomerular hypertension and hyperperfusion, leading to secondary epithelial cell abnormalities and, ultimately, FSGS. However, primary epithelial cell dysfunction caused by mitochondrial defects could not be ruled out on morphological grounds. MCs should be considered in cases of so-called primary FSGS, particularly if there is a familial history of diabetes, neuromuscular disorders, or deafness. (+info)Transient improvement of pyruvate metabolism after coenzyme Q therapy in Kearns-Sayre syndrome: MRS study. (5/60)
Coenzyme Q therapy has been used to support metabolic derangements in patients with mitochondrial encephalomyopathies. Biochemical analysis of the living human brain can be performed by magnetic resonance spectroscopy (MRS). We report upon a KSS patient who was serially imaged with localized proton MRS to monitor the efficacy of CoQ treatment. A 17-year-old girl with KSS was serially imaged with localized proton MRS performed on a GE 1.5 T SIGNA MRI/MRS system. The elevated lactate contents of lesions decreased after one month of CoQ therapy but were re-elevated 10 months after treatment. We conclude that MRS presents us with a powerful tool for monitoring the effects of therapeutic trials in mitochondrial encephalomyopathies. (+info)Kearns Sayre syndrome: an atypical presentation. (6/60)
Kearns Sayre syndrome is a rare presentation which usually involves a triad of factors: external ophthalmoplegia, retinal pigmentary degeneration, and heart block. We present a clinically and histopathologically confirmed case of Kearns Sayre syndrome that involved no retinal pathology. (+info)Neurological mitochondrial cytopathies. (7/60)
The mitochondrial cytopathies are genetically and phenotypically heterogeneous group of disorders caused by structural and functional abnormalities in mitochondria. To the best of our knowledge, there are very few studies published from India till date. Selected and confirmed fourteen cases of neurological mitochondrial cytopathies with different clinical syndromes admitted between 1997 and 2000 are being reported. There were 8 male and 6 female patients. The mean age was 24.42+/-11.18 years (range 4-40 years). Twelve patients could be categorized into well-defined syndromes, while two belonged to undefined group. In the defined syndrome categories, three patients had MELAS (mitochondrial encephalopathy, lactic acidosis and stroke like episodes), three had MERRF (myoclonic epilepsy and ragged red fibre myopathy), three cases had KSS (Kearns-Sayre Syndrome) and three were diagnosed to be suffering from mitochondrial myopathy. In the uncategorized group, one case presented with paroxysmal kinesogenic dystonia and the other manifested with generalized chorea alone. Serum lactic acid level was significantly increased in all the patients (fasting 28.96+/-4.59 mg%, post exercise 41.02+/-4.93 mg%). Muscle biopsy was done in all cases. Succinic dehydrogenase staining of muscle tissue showed subsarcolemmal accumulation of mitochondria in 12 cases. Mitochondrial DNA study could be performed in one case only and it did not reveal any mutation at nucleotides 3243 and 8344. MRI brain showed multiple infarcts in MELAS, hyperintensities in putaminal areas in chorea and bilateral cerebellar atrophy in MERRF. (+info)Executive and visuospatial deficits in patients with chronic progressive external ophthalmoplegia and Kearns-Sayre syndrome. (8/60)
Although neuropsychological deficits have been reported in mitochondrial cytopathies, patients with chronic progressive external ophthalmoplegia (CPEO) or Kearns-Sayre syndrome (KSS) have not been studied systematically using a comprehensive test battery. The aim of our study was to assess the range and extent of putative cognitive dysfunction in 22 patients with CPEO or KSS, and to compare cognitive performance of patients with healthy control subjects matched for age, sex and years of education. Genetic analysis of skeletal muscle tissue from 22 patients with CPEO or KSS included screening for mitochondrial DNA (mtDNA) point mutations (3243/8344) and mtDNA deletions. All patients were examined by a neuropsychological test battery covering verbal skills, verbal and visual memory, visuo-spatial perception, visual construction, attention, abstraction and flexibility, and Quality of Life. Molecular genetic analysis of mtDNA revealed single large-scale deletions in 15 out of 22 patients and the tRNA (Leu) A3243G point mutation in two out of 22 patients. In five out of 22 patients none of the frequently encountered mtDNA mutations could be detected. Neuropsychological testing did not reveal general intellectual deterioration, but specific cognitive deficits, particularly in visual construction, attention and abstraction/flexibility. Subgroup analysis of 15 patients with mtDNA deletions showed similar results when compared with the full group. In our series of patients with CPEO or KSS neuropsychological testing did not reveal signs that would suggest general intellectual decline or dementia, but provided evidence of specific focal neuropsychological deficits, suggesting particular impairment of visuospatial perception associated to parieto-occipital lobes and executive deficits associated to the prefrontal cortex. (+info)Kearns-Sayre Syndrome (KSS) is a rare, progressive genetic disorder that affects the function of the mitochondria, which are the energy-producing structures in cells. It is classified as a type of mitochondrial myopathy and is typically associated with symptoms that appear before the age of 20.
The medical definition of Kearns-Sayre Syndrome includes the following criteria:
1. Onset before 20 years of age
2. Progressive external ophthalmoplegia (PEO), which is characterized by weakness and paralysis of the eye muscles, leading to drooping eyelids (ptosis) and limited eye movement
3. Retinitis pigmentosa, a degenerative condition affecting the retina that can lead to vision loss
4. A cardiac conduction defect, such as heart block
5. Ragged red fibers on muscle biopsy
6. At least one major criteria or two minor criteria must be present:
* Major criteria include cerebellar ataxia (lack of coordination), deafness, or increased protein in the cerebrospinal fluid
* Minor criteria include pigmentary retinopathy, heart block, or a high level of creatine kinase in the blood.
Kearns-Sayre Syndrome is caused by a single large-scale deletion of genes in the mitochondrial DNA and is usually sporadic, meaning it occurs randomly and is not inherited from parents. The condition can be diagnosed through genetic testing, muscle biopsy, or other clinical tests. Treatment is focused on managing symptoms and may include physical therapy, surgery for ptosis, hearing aids, and pacemakers for heart block.
A syndrome, in medical terms, is a set of symptoms that collectively indicate or characterize a disease, disorder, or underlying pathological process. It's essentially a collection of signs and/or symptoms that frequently occur together and can suggest a particular cause or condition, even though the exact physiological mechanisms might not be fully understood.
For example, Down syndrome is characterized by specific physical features, cognitive delays, and other developmental issues resulting from an extra copy of chromosome 21. Similarly, metabolic syndromes like diabetes mellitus type 2 involve a group of risk factors such as obesity, high blood pressure, high blood sugar, and abnormal cholesterol or triglyceride levels that collectively increase the risk of heart disease, stroke, and diabetes.
It's important to note that a syndrome is not a specific diagnosis; rather, it's a pattern of symptoms that can help guide further diagnostic evaluation and management.
Kearns-Sayre syndrome
SDHD
SDHAF1
Ophthalmoparesis
Pearson syndrome
Cerebral folate deficiency
MELAS syndrome
Sweat gland
Magnesium deficiency
Mitochondrion
MT-TL1
Molecular lesion
Chronic progressive external ophthalmoplegia
TFAM
Retinitis pigmentosa
Mitochondrial DNA
Mitochondrial myopathy
Inborn errors of metabolism
Cerebral atrophy
List of neurological conditions and disorders
List of diseases (K)
List of neuromuscular disorders
KSS
Usher syndrome
Anita Harding
List of MeSH codes (C11)
List of MeSH codes (C18)
List of MeSH codes (C14)
List of syndromes
List of MeSH codes (C05)
Kearns-Sayre syndrome - Wikipedia
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MERRF2
- If myoclonic epilepsy with ragged red fibers (MERRF) syndrome is caused by at least one of four point mutations in mitochondrial DNA, then curing the disease should be as easy as giving new mitochondria to patients. (mitochondrialdiseasenews.com)
- myoclonic epilepsy and ragged-red fibers (MERRF) syndrome, and Kearns-Sayre syndrome (sporadic multisystem mitochondrial pathology). (ima-press.net)
Ragged red fi2
- Kearns-Sayre syndrome (KSS), oculocraniosomatic disorder or oculocranionsomatic neuromuscular disorder with ragged red fibers is a mitochondrial myopathy with a typical onset before 20 years of age. (wikipedia.org)
- Skeletal muscle biopsy revealed presence of ragged-red fibers, consistent with Kearns-Sayre syndrome. (stanford.edu)
Cerebrospinal fluid3
- citation needed] Kearns-Sayre patients are consistently found to have cerebral folate deficiency, a syndrome in which 5-MTHF levels are decreased in the cerebrospinal fluid despite being normal in serum. (wikipedia.org)
- The proposed cause of cerebral folate deficiency in the Kearns-Sayre syndrome is the failure of the mechanisms in the choroid plexus that are responsible for passage of folates from the serum to the cerebrospinal fluid. (wikipedia.org)
- Kearns-Sayre syndrome (KSS) is a rare mitochondrial DNA (mtDNA) deletion syndrome that typically presents before 20 years of age and is characterized by chronic progressive external ophthalmoplegia, pigmentary retinopathy, and a combination of cardiac conduction defects, cerebellar ataxia, and elevated cerebrospinal fluid protein levels. (nyu.edu)
Deletion4
- Kearns-Sayre syndrome (KSS) and Pearson's marrow-pancreas syndrome (PMPS) are rare disorders caused by the same molecular defect, one of several deletion mutations in mitochondrial DNA (mtDNA). (nih.gov)
- Mitochondrial DNA deletion in a girl with manifestations of Kearns-Sayre and Lowe syndromes: an example of phenotypic mimicry? (nih.gov)
- [ 5 ] The deletions vary in size and location on the mitochondrial genome in different individuals, although a common deletion of 4.9kB is present in at least a third of patients with Kearns-Sayre syndrome. (medscape.com)
- Kearns-Sayre syndrome (KSS) is a mitochondrial DNA deletion syndrome that presents with profound cerebral folate deficiency and other features. (biomedcentral.com)
Symptoms3
- We have studied a girl who presented with an oculocerebrorenal syndrome, but later developed symptoms and signs of mitochondrial encephalomyopathy. (nih.gov)
- Even if two individuals are affected by the same disease, such as Leigh syndrome, they may not have identical symptoms or causes of disease. (mitochondrialdiseasenews.com)
- If patients with Kearns-Sayre syndrome commonly are deficient in folate, logic would presume folinic acid therapy may benefit their symptoms. (mitochondrialdiseasenews.com)
Exercise intolerance1
- Mutations of mitochondrial DNA can lead to a number of illnesses including exercise intolerance and Kearns-Sayre syndrome (KSS), which causes a person to lose full function of their heart, eye, and muscle movements. (dadamo.com)
Phenotype1
- citation needed] Kearns and Sayre described patients with "pigmentary degeneration" on funduscopy, night vision abnormalities, and some histologic similarities, but also clinical differences, to retinitis pigmentosa Subsequently, the retinal phenotype of KSS was described as retinitis pigmentosa, atypical retinitis pigmentosa, tapetoretinal degeneration, salt-and-pepper retinopathy, and pigmentary retinopathy. (wikipedia.org)
CPEO4
- KSS is a more severe syndromic variant of chronic progressive external ophthalmoplegia (abbreviated CPEO), a syndrome that is characterized by isolated involvement of the muscles controlling movement of the eyelid (levator palpebrae, orbicularis oculi) and eye (extra-ocular muscles). (wikipedia.org)
- Pearson syndrome , which is a sideroblastic anemia of childhood, pancytopenia, and exocrine pancreatic failure, and chronic progressive external ophthalmoplegia (CPEO) , which consists of external ophthalmoplegia, bilateral ptosis, and proximal myopathy. (medscape.com)
- Chronic progressive external ophthalmoplegia (CPEO) is a rare clinical syndrome characterized by slowly progressive paralysis of extraocular muscles. (geometry.net)
- Chronic progressive external ophthalmoplegia (CPEO) is the most common characteristic of Kearns-Sayre syndrome, which is one member of the family of mitochondrial myopathies. (mitochondrialdiseasenews.com)
Pathophysiology1
- Describe the pathophysiology of ptosis for Horner syndrome. (nih.gov)
Disease4
- No disease-modifying therapy is available for Kearns-Sayre syndrome. (medscape.com)
- Lowe oculocerebrorenal syndrome is an X-linked recessive disease whose locus has been assigned to Xp25. (nih.gov)
- [ 1 ] However, in children, this condition most often has an idiopathic or genetic origin, such as 22q11.2 microdeletion syndrome, autoimmune polyglandular syn-drome type 1 (APS1), hypoparathyroidism-deafness-renal dysplasia (HDR) syndrome, hypoparathyroidism-retardation-dysmorphism (HRD) syndrome or mitochondrial disease. (medscape.com)
- Some differential diagnostic opportunities like Fahr's disease or Kearn Sayre's syndrome were also considered. (journal-imab-bg.org)
Deletions1
- Kearns Sayre Syndrome (OMIM #530000) occurs as a result of large-scale single deletions (or rearrangements) of mitochondrial DNA (mtDNA), which are usually not inherited but occur spontaneously, probably at the germ-cell level or very early in embryonic development. (medscape.com)
MELAS1
- Yet another pattern of regional metabolic abnormality was present in the MELAS syndrome, where proton spectroscopic imaging demonstrated focal localization of abnormally increased lactate/creatine and decreased N -acetylaspartate/creatine to the regions of the stroke-like lesions on conventional MR images. (neurology.org)
Manifestations1
- and mitochondrial myopathies, including Friedreich ataxia and Kearns-Sayre syndrome, with an emphasis on managing arrhythmic cardiac manifestations. (bvsalud.org)
Chronic1
- Neuropsychological testing of patients with chronic progressive external ophthalmoplegia and Kearns-Sayre Syndrome reveals distinct frontal and parieto-occipital deficits. (mpg.de)
DeaFness1
- Other aetiologies included hypoparathyroidism-deafness-renal dysplasia syndrome (5/37, 13·5%) and one patient each with autoimmune polyglandular syndrome type 1, Kearns-Sayre syndrome and Kenny-Caffey syndrome. (medscape.com)
Characteristic1
- However, it remains unclear how these changes could cause the recurrent episodes characteristic of cyclic vomiting syndrome. (medlineplus.gov)
Occurs1
- Kearns-Sayre syndrome occurs spontaneously in the majority of cases. (wikipedia.org)
Disorders2
- Turner syndrome must be differentiated from other similar conditions which lead to multiple endocrine disorders such as autoimmune polyendocrine syndrome , POEMS syndrome , Hirata syndrome, Kearns-Sayre syndrome and Wolfram syndromes . (wikidoc.org)
- Autism spectrum disorders (ASDs) - which include autistic disorder, Asperger's Syndrome, and pervasive developmental disorder-not otherwise specified (PDD-NOS) - are defined by behavioral observations and characterized by impairments in communication and social interaction, along with restrictive and repetitive behaviors [1]. (autismfile.com)
Pearson1
- in Pearson syndrome, mutations occur in hematopoietic cells, explaining the different clinical phenotypes. (medscape.com)
Leigh1
- For example, Leigh syndrome is associated with over 30 gene mutations, making it difficult to use single-gene identification as a cost-effective means of pinpointing Leigh syndrome. (mitochondrialdiseasenews.com)
Consistent1
- The regional brain metabolic abnormalities in patients with these syndromes showed different features consistent with the distinct phenotypes. (neurology.org)
Genetic1
- Several genetic syndromes-such as Fragile X and Rett syndromes-have been associated with ASD, but scientific studies have found that genetic syndromes are only observed in a small percentage (6-15 percent) of children with ASD [3]. (autismfile.com)
Rare1
- Duane syndrome (DS) is a rare, congenital eye movement disorder most commonly characterized by the inability of the eye to turn out. (bionity.com)
Horner2
- The varieties most commonly encountered by an ophthalmologist are 3rd cranial nerve palsy and Horner syndrome. (nih.gov)
- 21. What should be considered in a patient who has transient monocular vision loss and neck pain or ipsilateral Horner syndrome? (stanford.edu)
Abnormalities1
- Turner's syndrome must be differentiated from other diseases that cause latency in secondary sexual characteristics development, such as constitutional delay of puberty , hypopituitarism , delayed puberty , and chromosomal abnormalities . (wikidoc.org)
22q111
- Our cohort included 22 cases (59·5%) of 22q11·2 microdeletion syndrome. (medscape.com)
Patients with the syndrome2
- 11%). The investigators suggested therefore that formal electrophysiologic studies and prophylactic defibrillators be considered in patients with the syndrome. (medscape.com)
- Few patients with the syndrome complain of diplopia when their eyes are misaligned. (bionity.com)
Features1
- The clinical features of these syndromes have been extensively studied over the last decades. (biomedcentral.com)
Therapy1
- Quintos JB, Hodax JK, Gonzales-Ellis BA, Phornphutkul C, Wajnrajch MP, Boney CM. Efficacy of growth hormone therapy in Kearns-Sayre syndrome: the KIGS experience. (umassmed.edu)
Occur1
- Cushing's syndrome may occur due to excess adrenocorticotropic hormone. (gponline.com)
Cases1
- Some cases of cyclic vomiting syndrome, particularly those that begin in childhood, may be related to changes in mitochondrial DNA. (medlineplus.gov)