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Eduardo Bonilla - One of the best experts on this subject based on the ideXlab platform.

  • loss of myelin associated glycoprotein in Kearns Sayre Syndrome
    JAMA Neurology, 2012
    Co-Authors: Graham R. Campbell, Amy K Reeve, Jessica Zambonin, Emma L Blakely, Eduardo Bonilla, Kurenai Tanji, Salvatore Dimauro, Robert W Taylor, Nobuhiko Ohno, Evelyn Jaros
    Abstract:

    Objective To explore myelin components and mitochondrial changes within the central nervous system in patients with well-characterized mitochondrial disorders due to nuclear DNA or mitochondrial DNA (mtDNA) mutations. Design Immunohistochemical analysis, histochemical analysis, mtDNA sequencing, and real-time and long-range polymerase chain reaction were used to determine the pathogenicity of mtDNA deletions. Setting Department of Clinical Pathology, Columbia University Medical Center, and Newcastle Brain Tissue Resource. Patients Seventeen patients with mitochondrial disorders and 7 controls were studied from August 1, 2009, to August 1, 2010. Main Outcome Measure Regions of myelin-associated glycoprotein (MAG) loss. Results Myelin-associated glycoprotein loss in Kearns-Sayre Syndrome was associated with oligodendrocyte loss and nuclear translocation of apoptosis-inducing factor, whereas inflammation, neuronal loss, and axonal injury were minimal. In a Kearns-Sayre Syndrome MAG loss region, high levels of mtDNA deletions together with cytochrome- c oxidase–deficient cells and loss of mitochondrial respiratory chain subunits (more prominent in the white than gray matter and glia than axons) confirmed the pathogenicity of mtDNA deletions. Conclusion Primary mitochondrial respiratory chain defects affecting the white matter, and unrelated to inflammation, are associated with MAG loss and central nervous system demyelination.

  • a novel mitochondrial trnaleu uur mutation in a patient with features of merrf and Kearns Sayre Syndrome
    Neuromuscular Disorders, 2003
    Co-Authors: Yutaka Nishigaki, Eduardo Bonilla, Saba Tadesse, Dikoma C Shungu, Stephen P Hersh, Bronya J B Keats, Charles I Berlin, Morton F Goldberg, Jerry Vockley, Salvatore Dimauro
    Abstract:

    Abstract In a patient with clinical features of both myoclonus epilepsy ragged-red fibers (MERRF) and Kearns–Sayre Syndrome (KSS), we identified a novel guanine-to-adenine mitochondrial DNA (mtDNA) mutation at nucleotide 3255 (G3255A) of the tRNA Leu(UUR) gene. Approximately 5% of the skeletal muscle fibers had excessive mitochondria by succinate dehydrogenase histochemistry while a smaller proportion showed cytochrome c oxidase (COX) deficiency. In skeletal muscle, activities of mitochondrial respiratory chain complexes I, I+III, II+III, and IV were reduced. The G3255A transition was heteroplasmic in all tissues tested: muscle (53%), urine sediment (67%), peripheral leukocytes (22%), and cultured skin fibroblasts ( n =25) compared to COX-positive non-RRF (18%±9, n =21). The identification of yet another tRNA Leu(UUR) mutation reinforces the concept that this gene is a hot-spot for pathogenic mtDNA mutations.

  • Kearns Sayre Syndrome oncocytic transformation of choroid plexus epithelium
    Journal of the Neurological Sciences, 2000
    Co-Authors: Kurenai Tanji, Salvatore Dimauro, Eric A Schon, Eduardo Bonilla
    Abstract:

    Abstract Kearns–Sayre Syndrome (KSS) is a sporadic multisystem disorder due to a defect of oxidative phosphorylation and associated with clonally-expanded rearrangements of mitochondrial DNA (mtDNA) deletions (Δ-mtDNAs) and/or duplications (dup-mtDNAs). To gain further insight into the pathogenesis of CNS dysfunction in KSS, we studied the choroid plexus from two autoptic cases using in situ hybridization (ISH) of mtDNA, and immunohistochemistry to detect mtDNA and nuclear DNA-encoded subunits of the respiratory chain. Neuropathological examination of both cases showed oncocytic transformation of choroid plexus epithelial cells. In the same cells, ISH demonstrated that the predominant species of mtDNA were Δ-mtDNAs, and immunohistochemistry showed a decreased expression of mtDNA-encoded proteins. We suggest that mitochondrial abnormalities due to the presence of abundant Δ-mtDNAs in the choroid plexus play an important role in causing the increased cerebrospinal fluid (CSF) protein and reduced folic-acid levels that are characteristic of KSS.

  • disconnection of cerebellar purkinje cells in Kearns Sayre Syndrome
    Journal of the Neurological Sciences, 1999
    Co-Authors: Kurenai Tanji, Salvatore Dimauro, Eduardo Bonilla
    Abstract:

    Kearns-Sayre Syndrome (KSS) is a sporadic multisystem disorder due to rearrangements in mitochondrial DNA (mtDNA). To gain further insight into the pathogenesis of cerebellar dysfunction in KSS, antibodies against synaptophysin (SY) were used to identify presynaptic terminals and antibodies to calbindin D (CB) to identify Purkinje cells in the cerebellar cortex and in the dentate nucleus from two autopsied cases of KSS. By conventional neuropathology we found marked spongiform degeneration and by immunohistochemistry a disruption of presynaptic terminals and of the terminal arborizations of Purkinje cell axons on multipolar neurons of the dentate nucleus in the KSS patients. We suggest that a disconnection of Purkinje cells at the dentate nucleus may play a role in the pathogenesis of cerebellar ataxia in KSS.

  • Kearns Sayre Syndrome unusual pattern of expression of subunits of the respiratory chain in the cerebellar system
    Annals of Neurology, 1999
    Co-Authors: Kurenai Tanji, Salvatore Dimauro, Eric A Schon, Eduardo Bonilla
    Abstract:

    Kearns-Sayre Syndrome (KSS) is a sporadic multisystem disorder of oxidative phosphorylation associated with clonally expanded rearrangements of mitochondrial DNA (mtDNA). Mitochondrial dysfunction in the central nervous system of patients with KSS accounts for the neurological manifestations of the disease. To gain further insight into the pathogenesis of neuronal dysfunction in KSS, we used antibodies against mtDNA-encoded and nuclear DNA-encoded subunits of the mitochondrial respiratory chain to study the expression of these proteins in the cerebellar cortex, dentate nucleus, and inferior olivary nucleus from 2 autoptic cases of KSS. Neuropathological examination showed a moderate loss of Purkinje cells and spongiform degeneration of the cerebellar white matter. By using immunohistochemistry, we found a decreased expression of mtDNA-encoded proteins only in neurons of the dentate nucleus. We suggest that mitochondrial abnormalities in the dentate nucleus in conjunction with loss of Purkinje cells and spongiform degeneration of the cerebellar white matter may be important factors in the genesis of the cerebellar dysfunction in KSS.

Josef Finsterer - One of the best experts on this subject based on the ideXlab platform.

  • unusual phenotype and disease trajectory in Kearns Sayre Syndrome
    Case reports in neurological medicine, 2020
    Co-Authors: Josef Finsterer, Michael Winklehner, Claudia Stollberger, Thomas Hummel
    Abstract:

    Objective To describe unusual course and unusual phenotypic features in an adult patient with Kearns-Sayre Syndrome (KSS). Case Report. The patient is a 49-year-old male with KSS, diagnosed clinically upon the core features, namely, onset before the age 20 of years, pigmentary retinopathy, and ophthalmoparesis, and the complementary features, namely, elevated CSF protein, cardiac conduction defects, and cerebellar ataxia. The patient presented also with other previously described features, such as diabetes, short stature, white matter lesions, hypoacusis, migraine, hepatopathy, steatosis hepatis, hypocorticism (hyponatremia), and cataract. Unusual features the patient presented with were congenital anisocoria, severe caries, liver cysts, pituitary enlargement, desquamation of hands and feet, bone chondroma, aortic ectasia, dermoidal cyst, and sinusoidal polyposis. The course was untypical since most of the core phenotypic features developed not earlier than in adulthood. Conclusions KSS is a multisystem disease, but the number of tissues affected is higher than so far anticipated. KSS should be considered even if core features develop not earlier than in adulthood and if unusual features accompany the presentation.

  • Kearns-Sayre Syndrome MIGHT BE MIXED UP WITH CPEO PLUS
    MNJ (Malang Neurology Journal), 2019
    Co-Authors: Josef Finsterer, Sinda Zarrouk Mahjoub
    Abstract:

    In a recent article, Al Ghamdi presented a 40yo parturient with Kearns-Sayre Syndrome (KSS) who had received an implantable cardioverter defibrillator (ICD) because of an AVblock II (Mobitz 2 (2:1)) 11y earlier and underwent caesarean delivery for preeclampsia in local anesthesia with bupivacaine and fentanyl.(1) We have the following comments and concerns.

  • Kearns-Sayre Syndrome is genetically and phenotypically heterogeneous.
    La Pediatria medica e chirurgica : Medical and surgical pediatrics, 2018
    Co-Authors: Josef Finsterer, Sinda Zarrouk-mahjoub
    Abstract:

    Letter to the Editor Comment on : Kearns-Sayre Syndrome with facial and white matter extensive involvement: a (mitochondrial and nuclear gene related?) neurocristopathy? [Pediatr Med Chir. 2017]

  • Diagnosing Kearns-Sayre Syndrome Requires Genetic Confirmation.
    Chinese medical journal, 2016
    Co-Authors: Josef Finsterer, Sinda Zarrouk-mahjoub
    Abstract:

    To the Editor: With interest, we read the article by Kwon et al.[1] about a single patient with Kearns-Sayre Syndrome (KSS), who successfully and without complications underwent peripheral nerve block for multiple muscle biopsies. We have the following comments and concerns.

  • diagnose Kearns Sayre Syndrome genetically and investigate the phenotype comprehensively
    Oxford Medical Case Reports, 2016
    Co-Authors: Josef Finsterer, Sinda Zarroukmahjoub
    Abstract:

    Letter to the editor Comment on : Leal M Dhoble C Lee J Lopez D Menendez LS . A rare case of Kearns-Sayre Syndrome in a 17-year-old Venezuelan male with bilateral ptosis as the initial presentation. Oxf Med Case Reports 2016;2016:34–6.

G Rizzoni - One of the best experts on this subject based on the ideXlab platform.

  • bartter like phenotype in Kearns Sayre Syndrome
    Pediatric Nephrology, 2006
    Co-Authors: Francesco Emma, Carla Pizzini, Alessandra Tessa, Silvia Di Giandomenico, Andrea Onettimuda, Filippo M Santorelli, Enrico Bertini, G Rizzoni
    Abstract:

    Kearns–Sayre Syndrome (KSS) is a mitochondrial disease caused by large deletions in mitochondrial DNA (mtDNA). In most patients the disease is characterized by mtDNA heteroplasmy, where a mixture of wild-type and mutated mtDNA co-exist within cells in variable proportion, modulating the severity of the phenotype in different tissues. We report on the case of a 14-year-old child with classical symptoms of KSS and a renal phenotype characterized by hypokalaemic alkalosis, hypomagnesaemia, hyperreninaemia, hyperaldosteronism and nephrocalcinosis, resembling Bartter Syndrome. Analysis of mtDNA demonstrated an 8,661 bp deletion involving eight mitochondrial genes. Uneven degrees of mtDNA heteroplasmy were demonstrated in several tissues, ranging from 24% to 60% of deleted/total mtDNA. Variable degrees of expression of mitochondrial enzymes were also found in biopsy specimens of renal and skeletal muscle by histocytochemistry. In particular, preserved cytochrome c oxidase was observed in tubular structures within medullary rays. It is proposed that a “Bartter-like” phenotype can arise in some patients with KSS as a result of heteroplasmy. In these cases aldosterone-responsive tubular structures have been spared during renal embryogenesis, allowing for the development of hypokalaemic alkalosis in response to salt and water losses from the more damaged tubular segments.

Konstantinos Siogas - One of the best experts on this subject based on the ideXlab platform.

  • Kearns Sayre Syndrome associated with trifascicular block and qt prolongation
    International Journal of Cardiology, 2004
    Co-Authors: Pavlos Karanikis, Evaggelos Kountouris, Vasiliki Dimitroula, Dimitrios Patsouras, Eugenia Pappa, Panagiotis Korantzopoulos, Konstantinos Siogas
    Abstract:

    Patients suffering from Kearns-Sayre Syndrome (KSS) often develop conduction defects that may lead to syncope or sudden cardiac death. The association of conduction abnormalities with prolonged QT interval in these patients is very rare. We describe a patient with KSS and diabetes mellitus who suffered a torsades de pointes-induced syncopal attack, in the presence of trifascicular block and QT prolongation (QTc: 574 ms). The patient was successfully treated with permanent pacing. This case highlights that torsades de pointes represents a potential mechanism of syncope or sudden cardiac death in patients with KSS.

L Bindoff - One of the best experts on this subject based on the ideXlab platform.

  • clinical evolution of Kearns Sayre Syndrome with polyendocrinopathy and respiratory failure
    Acta Neurologica Scandinavica, 2007
    Co-Authors: L Bindoff, Petter Schandl Sanaker, Eystein S Husebye, O Fondenes
    Abstract:

    Background - The triad of progressive external ophthalmoplegia, atypical retinal pigmentation and cardiac conduction defects characterizes Kearns-Sayre Syndrome (KSS), which is most often caused by a single, large deletion of mitochondrial DNA. Endocrine disease appears to be more common in KSS than in other mitochondrial diseases. Materials, methods and results - A patient presenting with KSS developed Addison's disease, hypothyroidism and glucose intolerance. Thyroid peroxidase antibodies and adrenal 21-hydroxylase antibodies were identified. She developed acute respiratory failure requiring invasive ventilatory support, but improved and currently requires only non-invasive, nocturnal BiPAP treatment. Discussion and conclusion - This case confirms the association of KSS and endocrine dysfunction. Our finding of autoantibodies to thyroid and adrenal glands distinguishes this patient from most other published cases and suggests a potential synergy between the two disease mechanisms. In addition, we demonstrate that respiratory failure can be a treatable event in this disease.

  • Duplications of mitochondrial DNA in Kearns-Sayre Syndrome.
    Muscle & nerve. Supplement, 1995
    Co-Authors: J Poulton, K J Morten, D Marchington, K Weber, G K Brown, A Rötig, L Bindoff
    Abstract:

    mtDNA duplications were detectable in 10 of 10 patients with mtDNA deletions and Kearns-Sayre Syndrome (KSS) and in none of 8 patients with chronic progressive external ophthalmoplegia (CPEO). Thus, duplications of mtDNA seem to be a distinctive feature of KSS, including patients where Pearson's Syndrome is the first manifestation. Diabetes mellitus was identified in 4 of 7 patients with high or moderate levels of mtDNA duplications. The balance of mtDNA rearrangements may be central to the pathogenesis of this unique group of disorders.

  • are duplications of mitochondrial dna characteristic of Kearns Sayre Syndrome
    Human Molecular Genetics, 1994
    Co-Authors: J Poulton, K J Morten, K Weber, G K Brown, L Bindoff
    Abstract:

    The phenotypes of Kearns-Sayre Syndrome (KSS) and chronic progressive external ophthalmoplegia (CPEO) are closely associated with deletions of mitochondrial DNA (mtDNA). Recent evidence suggesting that more than one type of rearrangement may be present in KSS led us to reinvestigate 18 patients with KSS or CPEO for the presence of mtDNA rearrangements other than deletion. mtDNA duplication was detectable in 10 of 10 patients with KSS, while deletion monomers were the only recombinant mtDNA easily detectable in eight of eight patients with CPEO. Deletion dimers were found only in cases having duplications. Thus, duplications of mtDNA seem to be a hallmark of KSS, including a patient where Pearson's Syndrome was the first manifestation. We suggest that duplication of mtDNA is characteristic of the early-onset disease KSS, and that the balance of mtDNA rearrangements may be central to the pathogenesis of this unique group of disorders.