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Mitochondrial DNA Depletion Syndrome

mtDNA Depletion Syndrome


  • 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]
  • Seventeen patients presented with mtDNA depletion in liver or muscle, but the cause of mtDNA depletion still remains unknown in 8 of them.[ncbi.nlm.nih.gov]
  • Two infants, presenting with severe fatal hepatopathy. Raised serum lactate, positive family history (in first case), and absence of other causes of acute liver failure.[ncbi.nlm.nih.gov]
  • We present three patients from two apparently unrelated old colony Mennonite families, each of whom had the hepatocerebral form of MDS together with cystathioninuria.[ncbi.nlm.nih.gov]
Poor Feeding
  • Poor feeding, hypoglycaemia, raised serum lactate, hypotonia and faltering growth were common presenting features. mtDNA depletion in liver was demonstrated in all seven cases where liver tissue was available.[ncbi.nlm.nih.gov]
Long Arm
  • A high-density single-nucleotide polymorphism (SNP) array analysis revealed that the first patient had a region of copy-neutral absence of heterozygosity (AOH) consistent with segmental isodisomy for an 11.3 Mb region at the long-arm terminus of chromosome[ncbi.nlm.nih.gov]


Hepatocellular Carcinoma
  • One of our patients underwent liver transplantation; pathologic findings revealed (in addition to diffuse hepatopathy) a hepatocellular carcinoma, implying a possible link between mtDNA depletion syndrome and tumorigenesis.[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]
  • 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]
  • But his parents fought determinedly against this decision - raising more than 1.3million to pay for pioneering treatment in the US.[thesun.ie]


  • 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]
  • Clinically, patients homozygous for p.R50Q or compound heterozygous for the p.G94R and p.P98L mutations have a better prognosis, with all the other mutations associated with early death if not treated by liver transplantation.[ncbi.nlm.nih.gov]
  • CONCLUSION: Mutations in the MPV17 and DGUOK genes are present in a significant percentage of infants with liver failure and are associated with poor prognosis. Copyright 2014 Mosby, Inc. All rights reserved.[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]


  • 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]
Sex distribution
Age distribution


  • 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]


  • […] 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]
  • In this review, we discuss recent results demonstrating that enhancement of the salvage pathways by increasing the availability of deoxyribonucleosides needed for each specific genetic defect prevents mtDNA depletion.[ncbi.nlm.nih.gov]
  • Prevention of secondary complications: Dose reductions of medications metabolized by hepatic enzymes to avoid toxicity.[ncbi.nlm.nih.gov]
  • We used formulas enriched with medium-chain triglyceride content and fractional meals with enteral nutrition at night for adequate nutrition to prevent hypoglycemia. He continued to deteriorate rapidly, leading to death at 4 months of age.[journals.lww.com]
  • Treatment of manifestations: Physical therapy to maintain muscle function and prevent joint contractures; antiepileptic drugs for seizures; nasogastric or gastrostomy tube as needed to assure adequate caloric intake; chest physiotherapy, aggressive antibiotic[ncbi.nlm.nih.gov]

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