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]

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 the myopathic form of mitochondrial depletion syndrome (MDS) present with progressive weakness, hypotonia, and areflexia at or shortly after birth. [pediatricneurologybriefs.com]

• Recurrent Respiratory Infections

  Respiratory. Recurrent respiratory infections occur occasionally. Respiratory distress due to muscle weakness, obstructive sleep apnea, tracheomalacia, and abnormal breathing has also been reported. Skeletal. [ncbi.nlm.nih.gov]

• Progressive Dementia

  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]

• Progressive Intellectual Disability 

  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]

• Respiratory Distress

  The first patient developed intractable diarrhea, profound weakness, respiratory distress, and died at 3 months. The other two unrelated patients had a much milder phenotype and are still alive at ages 27 and 36 months. [ncbi.nlm.nih.gov]

• Recurrent Vomiting

  The feeding difficulties, recurrent vomiting, and gastroesophageal reflux disease can lead or contribute to failure to thrive in affected infants. [ncbi.nlm.nih.gov]

• Abnormal Eye Movement

  Hepatocerebral forms present with early-onset liver dysfunction and neurologic involvement, including developmental delay, abnormal eye movements, and peripheral neuropathy. [ncbi.nlm.nih.gov]

• Strabismus

  Other, less frequent, neurologic manifestations include hypertonia, choreoathetosis, ptosis, ophthalmoplegia, strabismus, and epilepsy (including infantile spasms and generalized convulsions). [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]

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]

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

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]

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]

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]

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]

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]

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]

Glucose metabolism and diet-based prevention of liver dysfunction in MPV17 mutant patients. J Hepatol 2009;50:215-21. [ PUBMED ] [ FULLTEXT ] 17. El-Hattab AW, Li FY, Schmitt E, Zhang S, Craigen WJ, Wong LJ. [saudijgastro.com]

[…] 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]

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]