Malabsorption due to exocrine pancreatic insufficiency Characteristics: Presents at during infancy or early childhood. [cme.ucsd.edu]

Myopathic MDS, caused by mutations in TK2, usually present before the age of 2 years with hypotonia and muscle weakness. [ncbi.nlm.nih.gov]

There are two main clinical presentations : myopathic and hepatocerebral. In the first group children present with devasting myopathy and neurological abnormalities. [ashg.org]

Patients with this mutation in their mitochondrial DNA have the mutation present in heteroplasmic form. [mitochondrialdisease.nhs.uk]

MDS is phenotypically heterogeneous, and can affect a specific organ or a combination of organs, with the main presentations described being either hepatocerebral (i.e. hepatic dysfunction, psychomotor delay), myopathic (i.e. hypotonia, muscle weakness [orpha.net]

• Anemia

  […] deficiency Congenital cataract-hypertrophic cardiomyopathy-mitochondrial myopathy syndrome Congenital cataract-progressive muscular hypotonia-hearing loss-developmental delay syndrome Congenital disorder of glycosylation Congenital dyserythropoietic anemia [se-atlas.de]

  Neuropathy, ataxia, and retinitis pigmentosa (NARP): Occurs in early childhood or adulthood Causes uncoordinated muscle movement (ataxia) and degeneration of the retina in the eye, leading to loss of vision Pearson’s syndrome: Occurs in infancy Causes severe anemia [neurosciences.uvahealth.com]

  Renal manifestations – glomerulopathy (focul segmental glomerulosclerosis) and tubolopathy that resembles Fanconi syndrome Hematologic manifestations - Bone marrow dysfunction with prominent sideroblastic anemia. [cme.ucsd.edu]

  MITOCHONDRIAL DNA DEFECTS IN NUCLEAR DNA AFFECTING MITOCHONDRIAL DNA OR ENZYME COMPLEXES PEO/multisystem with PEO KSS Pearson syndrome/KSS MELAS MERRF MiMyCa NARP/MILS LHON Diabetes, optic atrophy, deafness Tubulopathy, diabetes, ataxia Sideroblastic anemia [slideshare.net]

• Dysphagia

  Additional features: short stature, progressive ophthalmoplegia, cardiomyopathy, limb weakness, ataxia, retinitis pigmentosa, deafness, diabetes (hypoparathyroidism, growth hormone deficiency), endocrine dysfunction, dysphagia, and behavioral disorders [cme.ucsd.edu]

  Muscle weakness may also cause difficulty swallowing (dysphagia) and respiratory failure. Distal muscle weakness may be present but rarely seen early in the disease. [rarediseases.org]

  Notably, two siblings harboring DGUOK mutations displayed an atypical phenotype characterized by slowly progressive, predominantly distal, upper and lower limb muscle weakness, mild dysphonia and dysphagia, similarly to SMA-like presentations due to TK2 [mdpi.com]

• Heart Block

  Diagnosis: Atypical pigmentary retinopathy, ataxia, elevated cerebrospinal fluid protein, and heart block. Changes in muscle biopsy (RRF with the modified Gomori trichrome stain). [cme.ucsd.edu]

  His cardiac problems presented as episodic dizziness and congenital heart block that were noted in his late 20 s, with a pacemaker placed at 30 years of age. [frontiersin.org]

• Visual Impairment

  Visual impairment is often severe but the progression can plateau in early midlife and remains static as first reported by Behr. Systemic Features: A wide range of neurologic non-specific signs and symptoms may be present. [disorders.eyes.arizona.edu]

• Proximal Muscle Weakness

  muscle weakness, facial and bulbar weakness and failure to thrive. [orpha.net]

  The most typical presentation is progressive muscle disease characterized by generalized hypotonia, proximal muscle weakness, loss of previously acquired motor skills, poor feeding, and respiratory difficulties. TK2-MDS usually affects the muscles. [cags.org.ae]

  Mutations in the same gene have been more recently observed in adult phenotypes with ptosis, external ophthalmoplegia, slowly-progressive proximal muscle weakness, muscular atrophy and dysarthria [ 84, 85 ]. [mdpi.com]

• Muscle Hypotonia

  The patients seemed normal at birth and had an uneventful early development, apart from a mild to moderate muscle hypotonia. [cags.org.ae]

  Primary symptoms of the disease are developmental delay, progressive intellectual disability, hypotonia (low muscle tone), spasticity (stiffness of the limbs) possibly leading to quadriplegia, and progressive dementia. [en.wikipedia.org]

• Myalgia

  Case Report Since childhood, a 19-year-old woman complained of exercise-induced weakness and myalgia. She could not climb stairs or walk a block without stopping repeatedly. She also became short of breath with exertion. [rarediseases.org]

• Psychomotor Retardation

  retardation-progressive brain atrophy-basal ganglia disease syndrome Intermediate maple syrup urine disease Intermediate severe Salla disease Intermittent maple syrup urine disease Isobutyryl-CoA dehydrogenase deficiency Isolated ATP synthase deficiency [se-atlas.de]

• Stroke

  Mitochondrial Myopathy Symptoms Generally, mitochondrial myopathies cause: Muscle weakness or exercise intolerance Lack of balance or coordination Arryhthmias of the heart or heart failure Problems with eye movements Seizures Stroke-like episodes Vomiting [neurosciences.uvahealth.com]

  Background Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke (MELAS) syndrome is a multisystem and progressive neurodegenerative disorder. [emedicine.medscape.com]

  Other findings that may not be specific to mitochondrial disease include atrophy, white matter disease, and strokes. When clinicians see strokes that fall outside a blood vessel distribution, mitochondrial disease may be suspected. [childneurologyfoundation.org]

  Genetic Study of Pyruvate Dehydrogenase Complex Deficiencies Pyruvate Dehydrogenase Complex Deficiency DiseaseUniversity Hospitals Cleveland Medical Center | Rare Diseases Clinical Research Network | National Institute of Neurological Disorders and Stroke [mitoaction.org]

  The term refers to a group of muscle disorders, including: Kearns-Sayre syndrome (KSS) Leigh’s syndrome Mitochondrial Depletion syndrome (MDS) Mitochondrial Encephalomyopathy Lactic Acidosis and Stroke-like episodes (MELAS) Myoclonic epilepsy with Ragged [muscle.ca]

• Peripheral Neuropathy

  Finally, TYMP mutations have been associated with mitochondrial neurogastrointestinal encephalopathy (MNGIE) disease that typically presents before the age of 20 years with progressive gastrointestinal dysmotility and peripheral neuropathy. [ncbi.nlm.nih.gov]

  Other associated complications: optic atrophy, peripheral neuropathy, diabetes, cardiomyopathy, kidney and endocrine abnormalities. [cme.ucsd.edu]

  neuropathy Neuropathy, ataxia, and retinitis pigmentosa (NARP): Occurs in early childhood or adulthood Causes uncoordinated muscle movement (ataxia) and degeneration of the retina in the eye, leading to loss of vision Pearson’s syndrome: Occurs in infancy [neurosciences.uvahealth.com]

• Chronic Progressive External Ophthalmoplegia

  progressive external ophthalmoplegia (CPEO) in which the predominant clinical problem relates to an eye movement disturbance and ptosis. [jmg.bmj.com]

  progressive external ophthalmoplegia), KSS (Kearns-Sayre syndrome), Pearson marrow-pancreas syndrome and Leigh syndrome. [cme.ucsd.edu]

  Progressive External Ophthalmoplegia (CPEO) Danish patients between 18-80 years of age with verified single large-scale mtDNA deletions and chronic progressive external ophthalmoplegia. [mitoaction.org]

  Most often, patients with single deletions experience difficulty with eye movement (chronic progressive external ophthalmoplegia or CPEO) and develop droopy eyelids on one or both sides, beginning in early middle-age. [mitochondrialdisease.nhs.uk]

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

• Myoclonus

  […] stroke-like episodes, migraine headaches, vomiting and seizures, muscle weakness, exercise intolerance, hearing loss, diabetes and short stature Myoclonic epilepsy associated with ragged red fibers (MERRF): Occurs in late childhood to adulthood Causes myoclonus [neurosciences.uvahealth.com]

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

  There are several different types, including: Kearns-Sayre syndrome (KSS) chronic progressive external ophthalmoplegia (CPEO) Leber hereditary optic neuropathy (LHON) mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) myoclonus [musculardystrophyuk.org]

  Myoclonus may occur in association with generalized seizures. Other associated complications: optic atrophy, peripheral neuropathy, diabetes, cardiomyopathy, kidney and endocrine abnormalities. [cme.ucsd.edu]

  Myoclonus is a brief jerk that often happens first thing in the morning and can be a run of jerks. These jerks are sudden in onset and not necessarily associated with a loss of consciousness. [mitochondrialdisease.nhs.uk]

• Limb Weakness

  […] movement (ataxia) Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): Occurs before age 20 Causes eye movement problems (PEO), drooping eyelid, limb weakness, digestive problems and peripheral neuropathy Neuropathy, ataxia, and retinitis pigmentosa [neurosciences.uvahealth.com]

  Exercise intolerance, limb weakness, hearing loss, and diabetes may also precede the occurrence of the stroke-like episodes. [umdf.org]

  Additional features: short stature, progressive ophthalmoplegia, cardiomyopathy, limb weakness, ataxia, retinitis pigmentosa, deafness, diabetes (hypoparathyroidism, growth hormone deficiency), endocrine dysfunction, dysphagia, and behavioral disorders [cme.ucsd.edu]

  PEO is often associated with other signs of skeletal muscle involvement, typically slow progressive axial and proximal limb weakness affecting predominantly the hip and shoulder girdle muscles often with muscle wasting. [rarediseases.org]

  In adult non-syndromic clinical presentations, the involvement of skeletal muscle is mainly exhibited by external ophthalmoplegia, isolated or accompanied by limb weakness [ 3 ]. [mdpi.com]

His parents want to take him to the United States for an experimental treatment, but his doctors have disagreed, saying that the treatment would not help and would only extend Charlie's suffering. [livescience.com]

Orphan designation of the medicine has been granted in the United States for treatment of thymidine kinase 2 deficiency. [ema.europa.eu]

Treatment Treatment Options: No treatment has been reported. [disorders.eyes.arizona.edu]

Listing these organizations is not a recommendation or referral in any regard for seeking treatment or consultation or support for treatment. [chiarigear.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]

Overall, MDS are severe disorders with poor prognosis in the majority of affected individuals. No efficacious therapy is available for any of these disorders. [ncbi.nlm.nih.gov]

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]

PROGNOSIS Prognosis depends upon which disorder, which symptoms and the severity of those symptoms. Some of the conditions we thought were uniformly progressive and fatal are not (Leigh syndrome, for example). [childneurologyfoundation.org]

Prognosis MELAS syndrome widely varies in presentation; however, patients in general tend to have a poor prognosis and outcome. The encephalomyopathy tends to be severe and progressive to dementia. [emedicine.medscape.com]

Conversely, the absence of eye abnormalities may portend a better prognosis and a possible beneficial effect of liver transplantation. [journals.lww.com]

Characteristic Features Linked by a common etiology or pathogenesis – abnormal function of the mitochondria or deficient mitochondrial energy metabolism. [cme.ucsd.edu]

Houston Recruiting NCT02023866 Open-Label, Dose-Escalating Study to Assess Safety, Tolerability, Efficacy, PK and PD of RP103 in Children With Inherited Mitochondrial Disease Genetically diagnosed mitochondrial disease Raptor Pharma Completed NCT02003170 Etiology [mitoaction.org]

Clinically-based whole exome sequencing revealed the underlying etiology in the proband and his similarly affected sister to be a previously reported pathogenic mutation in the DES gene. [frontiersin.org]

International The first assessment of the epidemiology of mitochondrial disorders found a prevalence of more than 10.2 per 100,000 for the m.3243A → G mutation in the adult Finnish population. [emedicine.medscape.com]

The epidemiology of pathogenic mitochondrial DNA mutations. Ann Neurol 2000 ; 48 : 188 –93. ↵ Zeviani M, Moraes CT, DiMauro S, Nakase H, Bonilla E, Schon EA, Rowland LP. Deletions of mitochondrial DNA in Kearns-Sayre syndrome. [jmg.bmj.com]

The Epidemiology of Pathogenic Mitochondrial DNA Mutations. Annals of Neurology. 48(2): 188-193. Chinnery, PF (2003). Mitochondrial Disorders Overview. GeneTests. Obtained online Nov. 22, 2005 at www.genetests.org. Chinnery, PF, et al (2004). [cme.ucsd.edu]

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]

Sectors of interest are epidemiological and clinical-molecular correlation studies in mitochondrial diseases, assessment of biological and genetic markers in amyotrophic lateral sclerosis, Alzheimer’s disease and other genetic neuromuscular and neurodegenerative [rarediseases.org]

Pathophysiology Strokelike episodes and mitochondrial myopathy characterize MELAS syndrome. [emedicine.medscape.com]

[…] article is freely available re-usable Review Genes and Pathways Involved in Adult Onset Disorders Featuring Muscle Mitochondrial DNA Instability Neurology Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Dino Ferrari Centre, Department of Pathophysiology [mdpi.com]

Mr Preston said he advised Ms Yates that if she and Mr Gard took on Great Ormond Street, the hospital would likely use the courts to prevent Charlie from leaving the ward. [northwichguardian.co.uk]

Can Alper's be prevented? If the genetic faults are present, then there is nothing that can be taken during pregnancy or given to the infant that will prevent Alper's occurring. [mitochondrialdisease.nhs.uk]

[…] accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 15 March 2017 recommending the granting of this designation. the seriousness of the condition; the existence of alternative methods of diagnosis, prevention [ema.europa.eu]

The mutation leads to a reduction in the amount of mitochondrial DNA, and prevents the mitochondria from working properly. [livescience.com]

This is widely used for preventing many different genetic conditions being passed on, and as a result, thousands of healthy babies have been born. [musculardystrophyuk.org]