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

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]

Alpers syndrome is characterised by intractable epilepsy and liver dysfunction, but either problem can present in isolation. [adc.bmj.com]

• Weakness

  bulbar weakness), encephalomyopathic (i.e. hypotonia, muscle weakness, psychomotor delay) or neurogastrointestinal (i.e gastrointestinal dysmotility, peripheral neuropathy). [orpha.net]

  We describe a child with congenital muscle weakness who had a progressive mitochondrial myopathy associated with extensive fibro-fatty replacement of myofibers resembling muscular dystrophy. [ncbi.nlm.nih.gov]

  These are severe disorders presenting in early infancy or childhood with profound weakness encephalopathy, seizures and liver failure. [newcastle-mitochondria.com]

• Developmental Delay

  In infants, it results in the hepatocerebral phenotype, characterized by hyperbilirubinemia, coagulopathy, lactic acidosis, hypoglycemia, lethargy, encephalopathy, developmental delay, and hypotonia. [ncbi.nlm.nih.gov]

  In one form of ‘hepatocerebral’ depletion known as Alpers’ disease or Progressive Neuronal Degeneration of Childhood (PNDC), explosive onset of seizures, developmental delay and spasticity are followed some variable time later by catastrophic liver failure [newcastle-mitochondria.com]

  Onset is during infancy, and clinical features include liver dysfunction and failure, developmental delay, failure to thrive, lactic acidosis and muscle weakness. Rarer symptoms include seizures, ataxia, and liver cancer. [sema4genomics.com]

  Affected individuals also suffer from severe global developmental delay and a failure to thrive. [cags.org.ae]

• Feeding Difficulties

  Feeding difficulties, often necessitating tube feeding, occur commonly, while recurrent vomiting and gastroesophageal reflux disease occasionally occur. [ncbi.nlm.nih.gov]

  Myopathic MDS The symptoms of myopathic MDS usually appear in the first year of life and consist of feeding difficulties, failure to thrive, hypotonia, muscle weakness and, occasionally, PEO. [ijponline.biomedcentral.com]

• Fatigue

  Adult MDS manifest similarly to early-onset MDS, as myopathy, encephalo-myopathy, hepato-cerebral syndrome, or with chronic progressive external ophthalmoplegia (CPEO), fatigue, or only minimal muscular manifestations. [ncbi.nlm.nih.gov]

  You can improve muscle fatigue with regular gentle exercise. The condition can improve in a few patients with specific vitamins such as ubiquinone (coenzyme Q10) and riboflavin, but not in most. [musculardystrophyuk.org]

  Occasionally, patients may also have swallowing problems, palpitations and in common with other Mitochondrial Diseases, weakness and fatigue. [mitochondrialdisease.nhs.uk]

• Pathologist

  Back to top Leigh Syndrome Leigh disease ( syndrome ) is named after the pathologist (Denis Leigh) who first described the disease. [mitochondrialdisease.nhs.uk]

• Respiratory Insufficiency

  RRM2B -related mitochondrial disease should be suspected in the following Children with: Myopathy manifesting as muscle hypotonia and weakness, often associated with respiratory insufficiency Gastrointestinal disturbance manifesting as dysmotility Proximal [ncbi.nlm.nih.gov]

• Pneumonia

  A pioneering neuroscientist and highly respected pediatric neurologist, Peter Huttenlocher, professor emeritus and former section chief of pediatric neurology at the University of Chicago Medicine, died in Chicago of pneumonia and complications of Parkinson [news.uchicago.edu]

• Vomiting

  Common symptoms seen in Mitochondrial Neurogastrointestinal Encephalopathy disease (MNGIE) include digestive tract issues including nausea, inability to swallow easily, gastroesophageal reflux, vomiting after eating, abdominal pain and diarrhea. [thinkgenetic.com]

  However, he was admitted on the second day of life for 22 days because of poor feeding and repeated vomiting, and was seen to have episodes of unexplained hypoglycemia. He continued to have poor feeding and occasional episodes of vomiting. [saudijgastro.com]

  Other findings can include liver failure, renal tubular acidosis, pancreatitis, cyclic vomiting, and hearing loss. [ncbi.nlm.nih.gov]

• Nausea

  Common symptoms seen in Mitochondrial Neurogastrointestinal Encephalopathy disease (MNGIE) include digestive tract issues including nausea, inability to swallow easily, gastroesophageal reflux, vomiting after eating, abdominal pain and diarrhea. [thinkgenetic.com]

  acid reflux, All affected individuals develop weight loss and progressive gastrointestinal dysmotility manifesting as early satiety, nausea, diarrhea, vomiting, and stomach pain and swelling. [en.wikipedia.org]

  This may also include nausea, headache, light-headedness and heart palpitations. In severe cases, muscle weakness may be obvious, especially in small babies who may be very ‘floppy’ (hypotonia) and have difficulty breathing and feeding. [musculardystrophyuk.org]

  All affected individuals develop weight loss and progressive gastrointestinal dysmotility manifesting as early satiety, nausea, dysphagia, gastroesophageal reflux, postprandial emesis, episodic abdominal pain with distention, and diarrhea. [ijponline.biomedcentral.com]

• Muscle Weakness

  bulbar weakness), encephalomyopathic (i.e. hypotonia, muscle weakness, psychomotor delay) or neurogastrointestinal (i.e gastrointestinal dysmotility, peripheral neuropathy). [orpha.net]

  We describe a child with congenital muscle weakness who had a progressive mitochondrial myopathy associated with extensive fibro-fatty replacement of myofibers resembling muscular dystrophy. [ncbi.nlm.nih.gov]

• Myopathy

  In the case of TK2 deficiency, affected individuals suffer severe myopathy and, in the case of dGK deficiency, devastating liver or multi-systemic disease. [ncbi.nlm.nih.gov]

  For information on experimental results using Drosophila models of this and related diseases see mitochondrial myopathy, SLC25A4(ANT1)-related ( FBhh0000372 ). [flybase.org]

• Muscle Hypotonia

  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]

  Hypotonia, lactic acidosis, and proximal renal tubulopathy in association with mitochondrial respiratory chain defects and severe mtDNA depletion in skeletal muscle should prompt testing of RRM2B before other nuclear-encoded genes (in which muscle weakness [ncbi.nlm.nih.gov]

• Encephalopathy

  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]

  Indications for testing: Symptomatic individuals consistent with neurogastrointestinal encephalopathy forms of mitochondrial disease (MNGIE). [athenadiagnostics.com]

• Asthenia

  Pesce V, Cormio A, Marangi LC, Guglielmi FW, Lezza AM, Francavilla A, Cantatore P, Gadaleta MN 2002 Depletion of mitochondrial DNA in the skeletal muscle of two cirrhotic patients with severe asthenia. Gene 286 : 143–148 17. [doi.org]

• Paresis

  Autosomal recessive progressive external ophthalmoplegia (arPEO) is characterized by progressive weakness of the extraocular eye muscles resulting in ptosis and ophthalmoparesis (or paresis of the extraocular muscles) without associated systemic involvement [ncbi.nlm.nih.gov]

Because of the intense rarity of the condition, there are currently no widely available treatments for patients like Charlie. [frontlinegenomics.com]

His defiant parents had earlier vowed to fight for their baby in the hope of taking him to the US for the treatment. [zeenews.india.com]

She said life-support treatment would not benefit Charlie but "prolong the process of dying" and added: "This is not pioneering or life-sustaining treatment, but a purely experimental process with no real prospect of improving Charlie's condition or quality [standard.co.uk]

But his parents fought determinedly against this decision - raising more than £1.3million to pay for pioneering treatment in the US. [thesun.ie]

Very few people who develop the condition in infancy survive to their teenage years, and there is currently no known treatment for it. [metro.co.uk]

Liver failure and cardiorespiratory failure due to brain, spinal cord, and nerve involvement may also occur. x Prognosis The prognosis for individuals with Alpers' disease is poor. [ninds.nih.gov]

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]

These are severe disorders with poor prognosis in the majority of cases. So far, no therapy or cure exists to help patients, although nutritional interventions or supplementation can be beneficial for some children. [ibtimes.co.uk]

Abstract To highlight differences between early-onset and adult mitochondrial depletion syndromes (MDS) concerning etiology and genetic background, pathogenesis, phenotype, clinical presentation and their outcome. [ncbi.nlm.nih.gov]

Table 1 summarizes the main clinical manifestations and molecular etiologies associated with these different forms. [ijponline.biomedcentral.com]

The underlying etiology is not clear; it is possible that frequent episodes of severe dehydration and metabolic acidosis may play a role in its development. [saudijgastro.com]

Diseases Alpers disease must be differentiated from other mitochondrial diseases caused POLG gene mutation: Childhood Myocerbrohepatopathy Spectrum Disorder[7] Myoclonus epilepsy myopathy sensory ataxia (MEMSA) Progressive external ophthalmoplegia[8] Epidemiology [wikidoc.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]

It is proposed that EPR has a role in mechanistic pathophysiological studies of mitochondrial disease and could be used to study the impact of new treatment modalities or as an additional diagnostic tool. Copyright © 2016 Elsevier Inc. [ncbi.nlm.nih.gov]

Pathophysiology Alpers disease is inherited in an autosomal recessive pattern. [wikidoc.org]

[…] thymidine-induced mtDNA depletion in culture as a model of mitochondrial neurogastrointestinal encephalomyopathy, MNGIE), we show that supplements of those deoxyribonucleosides (dNs) involved in each biochemical defect (deoxyguanosine or deoxycytidine, dCtd) prevents [ncbi.nlm.nih.gov]

Primary Prevention There are no established measures for the primary prevention of Alpers disease. Secondary Prevention There are no established measures for the secondary prevention of Alpers disease. References ↑ Alpers, Bernard J. (1931). [wikidoc.org]