DOCSLIB.ORG

MITOCHONDRIAL News

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
MITOCHONDRIAL News UNITED MITOCHONDRIAL DISEASE FOUNDATION MITOCHONDRIAL NEWS TWO UMDF FUNDED RESEARCH smoking engine), Enns found that patients with a CONTENTS mitochondrial disorder had their natural antioxidant GRANTS RESULT IN NEW defense system overtaxed by the free radicals. INFORMATION “Even when these patients are coming into the Ask The Mito DocSM clinic looking pretty healthy, they have evidence of 3 One of the main mission points for the United extra metabolic stress,” Enns said, noting the findings Mitochondrial Disease Foundation is research. Since were surprising because none of the patients were Chapter Activities 1996, the UMDF has funded more than $6 Million in in the midst of a health crisis, such as organ failure, 4 research projects aimed at finding better treatments, when blood samples were drawn. diagnosis and ultimately a cure for mitochondrial “It is the first time such signs have been Fundraising Highlights disease. That is why we are excited about two recent uniformly shown in the blood of patients across 5-7 research projects that received a wide range of mitochondrial partial funding from the UMDF disorders,” he added. The team Adult Corner Research Grant Program. saw that levels of glutathione, the 9 In 2004, Gregory Enns, MD, body’s primary antioxidant, were ChB, and his team from Stanford significantly reduced in white blood Advocacy University School of Medicine cells from the 20 mitochondrial 10 and Lucile Packard Children’s disease patients in the study. Hospital were the recipients of a A second finding gave the Announcements grant for a project that devised a researchers information on potential 12 much needed way to monitor and treatments. They found that patients find treatments for mitochondrial taking antioxidant supplements did disorders. The team discovered not have depleted glutathione. This a biological marker that can be research may help understand the used to monitor mitochondrial effectiveness of supplements for a mitochondrial disease patient. “As a diseases. Dr. Gregory Enns “When a car engine doesn’t clinician, one of the most frustrating work right, it smokes,” said Dr. Enns, who is a things has been not being sure if supplements are professor of pediatrics at Stanford University School doing any good.” said Enns. “Now we are able to take of Medicine and director of the biochemical genetics a baseline blood reading and see ‘before’ and ‘after’ program at Packard. “What we looked for is, in snapshots,” Enns says glutathione measurements essence, biochemical smoke.” could help with a diagnosis by giving physicians The finding will enable researchers to hunt for a clear indication that something is wrong in the treatments and help patients’ status before health mitochondria. crises erupt. Patients who have a mitochondrial The method that the Enns team used to measure disorder were compared with healthy people in a glutathione, called high-dimensional flow cytometry, control group. Since defective mitochondria produce has limitations: it requires fresh blood samples, uses large quantities of oxygen-free radicals (like a (continued on page 2) The California Chapter held a family meeting prior to the 4th Annual Dinner and Silent Auction on March 7th. Pictured left is Norma Gibson, Brittany Wilkinson and Chuck Mohan. Volume 14 See pages 4-7 for Issue 1 more events and Spring 2009 fundraisers! www.umdf.org | 8085 Saltsburg Road, Suite 201 | Pittsburgh, PA 15239 | P 888•317•UMDF (toll-free) | P 412•793•8077 | F 412•793•6477 | [email protected] From Page one equipment only available in research labs and does by inactivating calcium-independent phospholipase not provide absolute glutathione measurements. A2, which prevents the degradation of cardiolipin,” Now that the team knows what metabolic change Dr. Ren told Mitochondrial News. His team’s method to look for, they’re working to develop a more broad would keep the cardiolipin levels normal. “This based measurement technique. is good news for patients because this enzyme In March 2009, researchers at NYU Langone (tafazzin) is now a potential target for therapeutic Medical Center announced that they may have intervention.” discovered a new targeted The research has not been National Office Staff intervention for Barth Syndrome tested in humans. Dr. Ren (BTHS). BTHS is a mitochondrial cautions that it shows promise Charles A. Mohan Jr., CEO/Executive Director disorder occurring mostly in but is still years away from being [email protected], ext. 111 males. BTHS leads to infection developed into a treatment. At Mark Campbell, Chief Financial Officer or heart failure in children and the present time, there are no [email protected], ext. 110 can be a fatal disease. Research treatments for Barth Syndrome lead by Mindong Ren, PhD, patients. Kara Strittmatter, Director of Member Services shows the benefits of a targeted As mentioned above, both [email protected], ext. 114 intervention with an iPLA2- projects were partially funded VIA inhibitor that prevents a by research grants from the Clifford Gorski, Director of Communications major symptom of the disease United Mitochondrial Disease [email protected], ext. 101 – cardiolipin deficiency. Foundation. “Those who support Carol Rush, PhD, Director of Development People affected with BTHS the UMDF through donations [email protected] have a defect in the cardiolipin Dr. Mindong Ren and fundraisers can now see metabolism which fights first hand how those dollars Scott Precopia, IT Manager infections. Additional symptoms may include a are allocated to the projects and programs that will [email protected], ext. 118 weak heart muscle, a reduction of white blood cells bring the best results for patients who suffer from Barbara Podowski, Administrative Assistant that fight bacterial infections, growth delay, and mitochondrial disorders,” said Charles A. Mohan, Jr., [email protected], ext. 100 an increase in organic acids in urine. In healthy Executive Director and CEO of the UMDF. “We are people, cardiolipin resides in the inner membrane of very excited about both projects as research moves Janet Owens, Executive Administrative Assistant the mitochondria and is responsible for normal cell us forward to a cure,” Mohan added. Findings from [email protected], ext. 107 structure and energy production. both projects demonstrate the urgency for federally BTHS is a debilitating heart and skeletal muscle funded research into mitochondrial dysfunction. Tania Hanscom, Communications Assistant disease that causes muscle weakness and fatigue “Dr. Enns and his research team have clearly shown [email protected], ext. 112 in those affected. Its cause is in a mutation in the that glutathione measurements may help scientists Bethany Neumeyer, Member Services Associate genetic coding of tafazzin. Tafazzin is an enzyme of unravel the causes of many other diseases with [email protected], ext. 104 the cardiolipin pathway. mitochondrial involvement such as poor vision, A previous study at NYU revealed the hearing loss, kidney disease, autism spectrum Melinda O’Toole, Member Services Associate characteristics of a tafazzin deficiency in a disorders, diabetes, Alzheimer’s, Parkinson’s and [email protected], ext. 103 fruit fly. The deficiency resulted in low and cancers. Our scientific and medical community Donna Nameth, Data Entry Manager abnormal cardiolipin concentration, abnormal has urged the Obama Administration to include [email protected], ext. 109 mitochondria, and poor motor function. In Dr. Ren’s research into mitochondrial medicine among his study, the research showed that the cardiolipin administration’s top medical and research priorities. Jean Bassett, Research Grants Coordinator deficiency disrupted the fruit fly’s final stage of UMDF members, families and friends must urge their [email protected], ext. 105 spermatogenesis causing male sterility. “Using congressional and senatorial representatives to do Ryan Fisher, Development Assistant this fly model, the study showed that this trait of the same.” [email protected], ext. 116 cardiolipin deficiency can be genetically suppressed Don Gielas, Grant Writer Gregory Enns, MB, ChB, was awarded a research grant in 2004 in the amount of [email protected], ext. 113 $34,179. His project was titled “GSH levels, reactive oxygen species production, Kylie Dunmire, Special Events Associate lipid peroxidation, products and mitochondrial membrane potential in patients with [email protected], ext. 108 mitochondrial disease.” Mindong Ren, PhD, was awarded a research grant in 2007 in the amount of UMDF Mission $157,450. His project was titled “Genotype-Phenotype Correlation and Genetic To promote research and education for the Modifiers in Barth Syndrome.” diagnosis, treatment and cure of mitochondrial For more information on the UMDF Research Grant Program, visit www.umdf.org. disorders and to provide support to affected individuals and families. 2 MITOCHONDRIAL NEWS - Vol. 14, Issue 1 ASK THE MITO DOCSM organs or tissues, at least in the majority of cases. often see developmental regression when seizures However, whether the donation is blood, tissue become longer in duration and/or more frequent. or organs, mitochondrial disease will not spread So, this can influence toilet training. Maybe better to non-donated organs/tissues. Mitochondrial seizure control would allow him to learn how to use the toilet. I say this ‘tongue in cheek,’ as I take care ASK THE disease is not “contagious.” In humans, genes do of so many mitochondrial patients with intractable SM not “jump” from one person to another or from one organ/tissue to another. epilepsy. I do hope that you can toilet train your son in the near future. MITO DOC THE QUESTION IS... We have been trying to toilet train our 11 year THE QUESTION IS... old son for many years. He was in underwear I have heard that tests are run on patients in the iving with mitochondrial disease presents during day-time hours for one year and had hospital on the basis of money rather than quality. L many twists and turns and a maze of some success, but his seizures increased How can we be sure we are getting appropriate questions.
Load more

Recommended publications
  • Leigh Disease Associated with a Novel Mitochondrial DNA ND5 Mutation
    European Journal of Human Genetics (2002) 10, 141 ± 144 ã 2002 Nature Publishing Group All rights reserved 1018-4813/02 $25.00 www.nature.com/ejhg SHORT REPORT Leigh disease associated with a novel mitochondrial DNA ND5 mutation Robert W Taylor*,1, Andrew AM Morris2, Michael Hutchinson3 and Douglass M Turnbull1 1Department of Neurology, The Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK; 2Department of Metabolic Medicine, Great Ormond Street Hospital, London, WC1N 3JH, UK; 3Department of Neurology, St Vincent's University Hospital, Dublin, Republic of Ireland Leigh disease is a genetically heterogeneous, neurodegenerative disorder of childhood that is caused by defects of either the nuclear or mitochondrial genome. Here, we report the molecular genetic findings in a patient with neuropathological hallmarks of Leigh disease and complex I deficiency. Direct sequencing of the seven mitochondrial DNA (mtDNA)-encoded complex I (ND) genes revealed a novel missense mutation (T12706C) in the mitochondrial ND5 gene. The mutation is predicted to change an invariant amino acid in a highly conserved transmembrane helix of the mature polypeptide and was heteroplasmic in both skeletal muscle and cultured skin fibroblasts. The association of the T12706C ND5 mutation with a specific biochemical defect involving complex I is highly suggestive of a pathogenic role for this mutation. European Journal of Human Genetics (2002) 10, 141 ± 144. DOI: 10.1038/sj/ejhg/5200773 Keywords: Leigh disease; complex I; mitochondrial DNA; mutation; heteroplasmy Introduction mutations in the tRNALeu(UUR) gene,3 and a G14459A Leigh disease is a neurodegenerative condition with a variable transition in the ND6 gene that has previously been clinical course, though it usually presents during early characterised in patients with Lebers hereditary optic childhood.
    [Show full text]
  • Consensus-Based Statements for the Management of Mitochondrial Stroke-Like Episodes[Version 1; Peer Review: 2 Approved]
    Wellcome Open Research 2019, 4:201 Last updated: 02 OCT 2020 RESEARCH ARTICLE Consensus-based statements for the management of mitochondrial stroke-like episodes [version 1; peer review: 2 approved] Yi Shiau Ng 1-3, Laurence A. Bindoff4,5, Gráinne S. Gorman1-3, Rita Horvath1,6, Thomas Klopstock7-9, Michelangelo Mancuso 10, Mika H. Martikainen 11, Robert Mcfarland 1,3,12, Victoria Nesbitt13,14, Robert D. S. Pitceathly 15,16, Andrew M. Schaefer1-3, Doug M. Turnbull1-3 1Wellcome Centre for Mitochondrial Research, Newcastle University, UK, Newcastle upon Tyne, Tyne and Wear, NE2 4HH, UK 2Directorate of Neurosciences, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, Tyne and Wear, NE1 4LP, UK 3NHS Highly Specialised Service for Rare Mitohcondrial Disorders, Royal Victoria Infirmary, Newcastle upon Tyne, UK 4Department of Clinical Medicine, University of Bergen, Bergen, Norway 5Department of Neurology, Haukeland University Hospital, Bergen, Norway 6Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK 7Department of Neurology, Friedrich-Baur-Institute, University Hospital of the Ludwig-Maximilians-Universität München, Munich, Germany 8German Center for Neurodegenerative Diseases (DZNE), Munich, Germany 9Munich Cluster for Systems Neurology (SyNergy), Munich, Germany 10Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa, Pisa, Italy 11Division of Clinical Neurosciences, University of Turku and Turku University Hospital, Turku, Finland 12Great North Children Hospital, Newcastle
    [Show full text]
  • Understanding and Coping with Mitochondrial Disease
    From the parents’ view … When we first heard that our daughter, Alexis, was diagnosed with Mitochondrial disease, we really didn't know what it was. We also learned that not too many people had heard of it before. Our daughter had many tests performed to reach the diagnosis of Mitochondrial disease. So once we received the news we were actually glad to finally have some answers. No parent wants their child to be ill, but we have learned to accept the disease and live with it on a day to day basis. We also learned that each person with Mitochondrial disease is affected differently by it. Alexis is severely affected by the disease, so each day with her is special. Meeting other children with Mitochondrial disease and their families have become a great support for us. We can relate to their daily struggles and if we need advice, they are there for us. My advice that I would give to others affected by Mitochondrial disease is to not give up. We can all fight this disease together. The hardest part sometimes is people not knowing enough about the disease. We really need to start educating people about it. Chris and Stephanie Understanding and coping with Mitochondrial disease A guide for parents The health care team at the Neuromuscular and Neurometabolic Centre wrote this book to answer some common questions about Mitochondrial disease. We hope that you will find it helpful. During your child’s care, you will meet the members of our team. We will work closely with you and your child to meet your needs.
    [Show full text]
  • How Do We Manage Stroke-Like Episodes?
    Mitochondrial diseases in adults: how do we manage stroke-like episodes? Dr Robert Pitceathly Senior Clinical Research Associate MRC Centre for Neuromuscular Diseases UCL, London Overview • Mitochondria and mitochondrial disease • What are stroke-like episodes? • Recognition of stroke-like episodes • Management of stroke-like episodes Mitochondria and mitochondrial disease The mitochondrion mtDNA and mitochondrial diseases 0 16,569 >250 pathogenic mutations Genetics of mitochondrial disease 37 genes > 1000 genes Genes of mitochondria-localised proteins linked to human disease Koopman WJ et al. N Engl J Med 2012;366:1132-1141 Genetic variability nDNA mtDNA 13 polypeptide subunits 7/44 0/4 1/11 3/14 2/16 Clinical variability Respiratory Failure Optic Atrophy / Retinitis Pigmentosa / Cataracts Cardiomyopathy / Conduction Defects CVA / Seizures / Developmental Delay Liver / Renal Failure Deafness Short stature / Marrow Failure Peripheral Diabetes Neuropathy Hypothyroidism Myopathy Clinical variability Age of onset Neonate Infant Child Adolescent Adult Elderly Congenital Lactic LS Acidosis PMPS HCM Alpers KSS MELAS CPEO MERRF NARP Exercise intolerance Myopathy How common is Mitochondrial Disease? Minimum point prevalence (mtDNA mutations): 1, in 5,000 Overt disease due to nDNA mutations: 2.9 per 100,000 Prevalence (total): 1 in 4,300 Mutation Affected ‘At Risk’ per 100,000 (CI) LHON 3.7 (2.9-4.6) 4.4 (3.7-5.3) m.3243A>G 3.5 (2.7-4.4) 4.4 (3.7-5.3) mtDNA 1.5 (1.0-2.1) 0 deletion m.8344A>G 0.2 (0.1-0.5) 0.5 (0.2-0.8) SPG7, ar 0.8 (0.5-1.3) 1.3
    [Show full text]
  • Migraines: Genetic Studies Pietro Cortelli Mirella Mochi and Some Practical Considerations
    J Headache Pain (2003) 4:47–56 DOI 10.1007/s10194-003-0030-0 EDITORIAL Pasquale Montagna The “typical” migraines: genetic studies Pietro Cortelli Mirella Mochi and some practical considerations Abstract Epidemiological genetic, in the inflammation cascade; etc.) family and twin studies show that the did not result in uniformely accepted typical migraines carry a substantial findings. Linkage and genome wide genetic risk; they are currently con- scans gave evidence for several ceptualized as complex genetic dis- genetic susceptibility loci, still how- ౧ P. Montagna ( ) • M. Mochi eases. Several genetic association ever in need of confirmation. Careful Department of Clinical Neurosciences, University of Bologna Medical School, and linkage studies have been per- dissection of the clinical phenotypes Via Ugo Foscolo 7, I-40123 Bologna, Italy formed in the typical migraines. and trigger factors shall greatly help e-mail: [email protected] Candidate gene studies based on “a future efforts in the quest for the Tel.: +39-051-6442179 priori” pathogenic models of genetic basis of the typical Fax: +39-051-6442165 migraine (migraine as a calcium migraines. P. Cortelli channelopathy; a mitochondrial Department of Neurology, DNA disorder; a disorder in the University of Modena and Reggio Emilia, metabolism of serotonin or Key words Migraine • Aura • Modena, Italy dopamine; in vascular risk factors or Genetics • Cardiovascular risk prove heritability, since it may result from shared envi- “Typical” migraine as a complex disease: genetic ronmental factors. It is therefore interesting to note that at epidemiology, twin and segregation analysis studies least one genetic epidemiology survey found an increased disease risk for migraine in first-degree relatives com- That migraine runs in families is an ancient observation.
    [Show full text]
  • What Are Mitochondria and Mitochondrial Disease? What Does It Mean for Dysautonomia?
    The Basics: What Are Mitochondria and Mitochondrial Disease? What Does It Mean For Dysautonomia? Richard G. Boles, M.D. Medical Director, Courtagen Life Sciences, Inc. Woburn, Massachusetts Medical Geneticist in Private Practice Pasadena, California Dysautonomia International; 18-July, 2015 Herndon, Virginia Disclosure: Dr. Boles wears many hats Dr. Boles is a consultant for Courtagen, which provides diagnostic testing. • Medical Director of Courtagen Life Sciences Inc. – Test development – Test interpretation – Marketing • Researcher with prior NIH and foundation funding – Studying sequence variation that predispose towards functional disease – Treatment protocols • Clinician treating patients – Interest in functional disease (CVS, autism) (((((((((((( ! Ri chard G. Boles, M.D. – Geneticist/pediatrician 20 years at CHLA/USC! Medical Genetics ! Pasadena, California – In private practice since 2014 ! ( ! ( Richard(G.(Boles,(MD( 1( ( July(16,(2014(( Disclosure: Off-label Indications There are no approved treatments for mitochondrial disease. Everything is “off label” Payton, 15-year-old • Presented to my clinic at age 11 years. • Cyclic vomiting syndrome from ages 1-10 years, with 2-day episodes twice a month of nausea, vomiting and lethargy. • Episodes had morphed into daily migraine. • Chronic pain throughout her body. • Chronic fatigue syndrome = chief complaint. • Substantial bowel dysmotility/IBS Multiple admissions for bowel clean-outs. • Excellent student • Pedigree: probable maternal inheritance 4 TRAP1-Related Disease (T1ReD) Mitochondrion, 2015 • NextGen sequencing at age 14 years revealed the p.Ile253Val variant in the TRAP1 gene. • TRAP1 encodes a mitochondrial chaperone involved in antioxidant defense. • This patient is one of 26 unrelated cases identified by Courtagen to date who have previously unidentified disease associated with mutations in the ATPase domain.
    [Show full text]
  • Predisposition to Infection and SIRS in Primary Mitochondrial Disorders: 8 Years’ Experience in an Academic Center
    Predisposition to infection and SIRS in primary mitochondrial disorders: 8 years’ experience in an academic center Target Audience: patients and families affected by primary mitochondrial disorders, primary care providers Melissa A. Walker MD, PhD, Katherine B. Sims MD, Jolan E. Walter MD, PhD Massachusetts General Hospital, Boston, MA Infection and Immune Function in Primary Mitochondrial Disorders • Introduction • Primary mitochondrial disorders • The immune system • Review of MGH mitochondrial patient registry (8 years’ experience) • Patients & diagnoses • Experience with • Infections • System immune response syndrome (SIRS) • Immunodysfunction • Clinical implications & future directions Primary Mitochondrial Disorders • Cause: dysfunction of the mitochondrion, the “powerhouse” organelle of the cell • Mitochondrial functions • Oxidative-phosphorylation (energy production) • Fatty acid oxidation (energy metabolism) • Apoptosis (controlled cell death) • Calcium regulation • Epidemiology • Estimated ~1:4000 individuals affected Diagnosis of Primary Mitochondrial Disorders Goal: determine the probability and possible cause of primary mitochondrial disease • Problems: • No single way to diagnose • Can affect multiple organ systems • No definitive biomarker (blood test) • Not all genes known • Phenotypic variation (same gene, different symptoms) • Heteroplasmy (unequal distribution of mitochondria & their DNA in cells) & maternal inheritance • Secondary mitochondrial dysfunction can mimic primary mitochondrial disorders Diagnosis of Primary
    [Show full text]
  • Summary – Pain Dr. Irina Anselm
    Summary – Pain Dr. Irina Anselm Pain is a very common feature of any chronic disease and patients with mitochondrial disease frequently suffer from different types of pain. Almost any organ or system may be involved in patients with Mito, and thus they may have a variety of pains. Pediatric pain in particular is a very difficult area, as it is very hard for physicians to watch children suffering. Up until a few years ago there was not much information on how to approach and assess pain in children who are very young or those who are nonverbal. However, research now indicates that the best gauge of pain in both children and adults is patient (or parent) report, and that children should be treated for suspected pain. What types of pain or pain syndromes are most frequently seen in children and in adults with Mito? I. Headaches are very common. Patients may suffer from migraines, tension headaches, chronic daily headaches and combinations of these. Are mechanisms of these headaches different from those in patients who don't have mitochondrial disorders? No one can answer this question with 100% certainty. My approach to the treatment of headaches in individuals with mitochondrial disease is not that much different from our approach to headache in other patients with several exceptions: • Treatment is based on frequency and severity of the headaches. For example, if they occur once or even twice a month, it is probably not worth treating the patient with prophylactic medicine. Prophylactic or preventive approach means that the patient takes medication every day.
    [Show full text]
  • Diagnosis of Mitochondrial Diseases: Clinical and Histological Study of Sixty Patients with Ragged Red Fibers
    Original Article Diagnosis of mitochondrial diseases: Clinical and histological study of sixty patients with ragged red fibers Sundaram Challa, Meena A. Kanikannan*, Murthy M. K. Jagarlapudi**, Venkateswar R. Bhoompally***, Mohandas Surath*** Departmetns of Pathology and *Neurology, Nizam’s Institute of Medical Sciences, Hyderabad. **Institute of Neurological Sciences, Care Hospital, ***L.V. Prasad Eye Institute, Hyderabad, India. Background: Mitochondrial diseases are caused by muta- group of patients. tions in mitochondrial or nuclear genes, or both and most Key Words: Mitochondrial disease, Ragged-red fiber, Pro- patients do not present with easily recognizable disorders. gressive external ophthalmoplegia, Kearns-Sayre syndrome, The characteristic morphologic change in muscle biopsy, Myoclonus epilepsy with ragged-red fibers, Heart block. ragged-red fibers (RRFs) provides an important clue to the diagnosis. Materials and Methods: Demographic data, pre- senting symptoms, neurological features, and investigative findings in 60 patients with ragged-red fibers (RRFs) on muscle biopsy, seen between January 1990 and December Introduction 2002, were analyzed. The authors applied the modified res- piratory chain (RC) diagnostic criteria retrospectively to de- Mitochondrial diseases with ragged-red muscle fibers (RRF) termine the number of cases fulfilling the diagnostic criteria as well as some without RRF, are caused by mutations in mi- of mitochondrial disease. Results: The most common clini- tochondrial or nuclear genes, or both, which are normally in- cal syndrome associated with RRFs on muscle biopsy was volved in the formation and maintenance of a functionally in- progressive external ophthalmoplegia (PEO) with or with- tact oxidative phosphorylation system in the mitochondrial out other signs, in 38 (63%) patients. Twenty-six patients inner membrane.1 These disorders present, with bewildering (43%) had only external ophthalmoplegia, 5 (8%) patients array of clinical presentations and are usually dominated by presented with encephalomyopathy.
    [Show full text]
  • Lennox-Gastaut Syndrome in Mitochondrial Disease
    Original Article Yonsei Med J 2019 Jan;60(1):106-114 https://doi.org/10.3349/ymj.2019.60.1.106 pISSN: 0513-5796 · eISSN: 1976-2437 Lennox-Gastaut Syndrome in Mitochondrial Disease Soonie Lee1*, Min-Seong Baek1*, and Young-Mock Lee1,2 1Department of Pediatrics, Yonsei University College of Medicine, Seoul; 2Epilepsy Research Institute, Yonsei University College of Medicine, Seoul, Korea. Purpose: Previous studies have shown that neurologic symptoms are dominant in patients with mitochondrial diseases, and most of these patients have seizure-related disorders. The epileptic classification of these patients as Lennox-Gastaut syndrome (LGS) is as high as 25%. This study aimed to investigate the clinical manifestations, diagnoses, treatments, and epilepsy in LGS, which is associated with mitochondrial disease. Materials and Methods: A retrospective study was conducted on 372 patients who were diagnosed with mitochondrial disease between 2006 and 2016. Of these 372 patients, 40 patients diagnosed with LGS were selected, and they were classified into two groups based on the history of West syndrome. Patient characteristics were reviewed, and associations between clinical factors and outcomes after the treatment were analyzed. Results: The proportion of individuals with mitochondrial disease with LGS with a history of West syndrome was 32.5%. Among the patients with mitochondrial disease with LGS, neonatal seizure (p=0.029), seizure as the first symptom (p=0.018), and gener- alized paroxysmal fast activity frequency on electroencephalogram (p=0.018) in the group with a history of West syndrome were statistically significantly high. The first symptom onset (0.6±0.4 yrs vs. 1.6±0.9 yrs, p=0.003) and first seizure onset (0.9±0.7 yrs vs.
    [Show full text]
  • Maternally Inherited Diabetes and Deafness (MIDD) Syndrome with M.3243A>G Mutation Associated with Renal Failure — a Case Report
    CASE REPORT ISSN 2450–7458 Grzegorz Kade1, Sebastian Krzysztof Spaleniak2, Bogdan Brodacki3, Agnieszka Pollak4, Dariusz Moczulski2, Monika Ołdak4, Marek Saracyn5 1Department of Internal Medicine, Nephrology and Dialysis, Military Institute of Medicine, Warsaw, Poland 2Department of Internal Medicine and Nephrodiabetology, Medical University of Lodz, Poland 3Neurological Clinic, Military Institute of Medicine, Warsaw, Poland 4Department of Genetics, Institute of Physiology and Pathology of Hearing, Warsaw, Poland 5Department of Endocrinology and Isotope Therapy, Military Institute of Medicine, Warsaw, Poland Maternally inherited diabetes and deafness (MIDD) syndrome with m.3243A>G mutation associated with renal failure — a case report ABSTRACT before as a cause of renal failure in MIDD patients. Maternally-inherited diabetes with deafness (MIDD) (Clin Diabetol 2020; 9; 6: 475–478) is a rare form of monogenic diabetes that results, in most cases, from an A-to-G transition at position 3243 Key words: mitochondrial diabetes, sensorineural of mitochondrial DNA (m.3243A>G). The clinical pres- deafness, m.3243A>G mutation, renal failure, entation of m.3243A>G mutation is variable, ranging incomplete distal renal tubular acidosis from mild to severe phenotypes. Diabetes is often accompanied by sensorineural deafness, cardiomyo- Introduction pathy, neuromuscular, psychiatric disorders, macular The relationship between the m.3243A>G muta- dystrophy and renal failure (kidney manifestations in tion and maternally inherited diabetes mellitus and adults presenting with this mutation remain poorly deafness syndrome (MIDD) was first described in 1992 defined). by Ballinger et al. [1] Another disease associated with The study presents a case of a 40-years-old woman this mitochondrial mutation is MELAS syndrome (mito- with a history of bilateral sensorineural deafness, chondrial encephalopathy, lactic acidosis, and stroke- renal failure and diabetes that was diagnosed due to like episodes) which has been described by Pavlakis et increasing muscle weakness during exercise.
    [Show full text]
  • A Novel Mitochondrial DNA Deletion in a Chinese Girl with Kearns-Sayre
    CASE A novel mitochondrial DNA deletion in a Chinese girl REPORT with Kearns-Sayre syndrome Eric KC Yau 丘健昌 KY Chan 陳國燕 Kearns-Sayre syndrome is a rare disorder often caused by mitochondrial DNA rearrangement. KM Au 區鑑明 The most commonly reported mitochondrial DNA deletion is 4977 bp in size spanning TC Chow 周達倉 nucleotides 8469 and 13447. The clinical signs of Kearns-Sayre syndrome include chronic YW Chan 陳恩和 progressive external ophthalmoplegia, retinitis pigmentosa, heart block and cerebellar ataxia, as well as other heterogeneous manifestations including neuromuscular problems and endocrine disorders. Cardiac conduction defects can develop insidiously, leading to sudden death sometimes if not promptly recognised. This report focuses on the diagnosis of Kearns- Sayre syndrome in a Chinese girl who presented initially with short stature, delayed puberty, insidious onset of ptosis and later with typical features of Kearns-Sayre syndrome including complete heart block. Genetic analysis disclosed a novel 7.2 kilobases deletion in muscle tissue. Mitochondrial diseases have heterogeneous phenotypes and mutational analysis has proven to be an effective tool for confirming the diagnosis. Introduction Kearns-Sayre syndrome (KSS) is a rare mitochondrial disorder with multisystem involvement affecting the eye, muscle, heart, endocrine, peripheral and central nervous systems. Typical clinical features include ptosis, ophthalmoplegia, pigmentary retinopathy, cardiac conduction defects and/or cardiomyopathy, sensorineural deafness, myopathy, ataxia, developmental delay or regression, and endocrine disorders.1 Most deletions have been 4977 bp in size.2 We report here a young Chinese girl with a clinical diagnosis of KSS associated with a novel large-scale mitochondrial DNA (mtDNA) deletion. Case report The patient was the only child of non-consanguineous Chinese parents.
    [Show full text]