Symptoma

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]

  • Recurrent Respiratory Infections

    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]

  • 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]

  • 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]

  • 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]

  • Epicanthal Folds

    Patients may display variable facial dysmorphia such as a narrow elongated face, protruding malformed ears, epicanthal folds and downslanting palpebral fissures of the eyes with thick eyebrows, a saddle nose, and an everted lower lip. [cags.org.ae]

  • Quadriplegia

    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]

  • Liver Biopsy

    Histological changes on liver biopsy include fatty degeneration, bile duct proliferation, fibrosis and collapse of lobular architecture. [ijponline.biomedcentral.com]

    The hepatic mitochondrial DNA depletion syndrome: ultrastructural changes in liver biopsies. Hepatology 2001;34:776–784. PubMed CrossRef Google Scholar 59. Spinazzola A, Viscomi C, Fernandez-Vizarra E, et al. [doi.org]

    The hepatic mitochondrial DNA depletion syndrome: ultrastructural changes in liver biopsies. Hepatology. 2001; 34 :776–784. doi: 10.1053/jhep.2001.27664. [ PubMed ] [ CrossRef ] [ Google Scholar ] 59. [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]

Treatment [ edit ] There are no treatments for MDDS, but some of the symptoms can be managed. For survivors living with MDDS, there are drugs to control epilepsy, and physical therapy can help with muscle control. [en.wikipedia.org]

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

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]

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]

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]

[…] 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]

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]