Downloaded 467 times
Uploaded byMahmoud Alaaeldin Hashim, MD.
Mitochondrial diseases overview!
This document provides an overview of mitochondrial disorders including their characteristics, inheritance patterns, clinical presentations, diagnostic process, and treatment approaches. Mitochondrial disorders are caused by dysfunction of the mitochondrial respiratory chain and can affect multiple organ systems. Diagnosis involves considering the patient's history, symptoms, family history, laboratory and imaging testing, and potentially muscle biopsy. While there is no proven effective treatment, symptomatic management and supportive therapies like exercise, respiratory chain cofactors, antioxidants, and correcting secondary deficits may help address certain aspects of these complex, multi-system disorders.
More Related Content
Similar to Mitochondrial diseases overview!
Mitochondrial diseases overview!
- 1. Mahmoud A. Hashim Visitingstudent at upstate Medical University Final year student at Ainshams university – School of medicine Ahmed Mohamed Visiting student at upstate Medical University Final year student at Ainshams university – School of medicine Presented in PICU Department
- 2. Are cellularorganelles responsible for oxidative phosphorylation, which produces energy in the form of adenosine triphosphate (ATP). Only defects in the respiratory chain that impair oxidative phosphorylation are considered to be primary mitochondrial disorders.
- 3. A groupof disorders Caused by Pathologic dysfunction of the Mitochondrial respiratory chain Present with a wide range of clinical expression. Organ systems relying most on aerobic metabolism are affected. Involvement of the nervous system in general is common.
- 4. More than70 different polypeptides interact on the inner mitochondrial membrane to form the respiratory chain. The majority of subunits are synthesized within the cytosol from nuclear gene transcripts, but 13 essential subunits are encoded by the mitochondrial DNA (mtDNA).
- 5. A) Maternal Inheritance A mother with a mitochondrial DNA gene mutation will pass this abnormal gene to all of her children. The children will all be affected, with different degrees of severity.
- 6. More than70 different polypeptides interact on the inner mitochondrial membrane to form the respiratory chain. The majority of subunits are synthesized within the cytosol from nuclear gene transcripts, but 13 essential subunits are encoded by the mitochondrial DNA (mtDNA).
- 7. Mitochondrial diseasecan be passed on only if BOTH the mother and father are “carriers”. This means that they carry the mutated gene, but not the disease.
- 8. If one parenthas dominant nuclear DNA gene mutation This abnormal gene will be passed on to 50% of his/her children.
- 10. Mitochondrial diseasemay present with “any symptom in any organ at any age” Some mitochondrial disorders affect a single organ, but many involve multiple organ systems and often present with prominent neurologic and myopathic features. Many individuals display a group of clinical features that fall into a discrete clinical syndrome.
- 12. The mostcommon presentation of mitochondrial disease was an Encephalomyopathic form . Isolated or combined symptoms and signs of encephalopathy, seizures, hypotonia, and/or ophthalmopathy (53 %). Other presentations included a hepato-intestinal form in 25 %, a cardiac form manifesting mainly as early fatal cardiomyopathy in 16 %, and Barth syndrome (X-linked cardiomyopathy, mitochondrial myopathy and cyclic neutropenia) in 6 %.
- 13. Mitochondrial dysfunctionshould be considered as a differential diagnosis of any progressive multisystem disorder. Diagnosis is complex and requires the integration of information obtained by history, laboratory testing, imaging, and muscle biopsy. The outcome of this process is a statement of how probable it is that the patient has a primary mitochondrial disease on a scale ranging from “unlikely” to “definite.” In between are “possible” and “probable” mitochondrial disease designations.
- 14. A majorclue to mitochondrial disease is a history of multisystem involvement, especially in organs that requires great amount of energy. One of the major clues to mitochondrial disease is a clear family history of the same disorder, particularly in cases of maternal transmission only. The examination of a patient with suspected mitochondrial disease should look for evidence of the following Optic atrophy and Pigmentary retinopathy Cardiac enlargement Central nervous system findings Peripheral nervous system findings
- 15. Tests Performed EKGSerum Lactate EEG& EMGSerum CK MRI & MRSSerum Fasting Glucose LFTs & KFTs
- 16. I. Muscle Biopsy A biopsy of skeletal muscle permits histopathology, electron microscopy, respiratory chain enzymology, and mtDNA testing. The classic hallmark of mitochondrial diseases is subsarcolemmal and intermyofibrillar accumulation of mitochondria visualized on Gomori trichrome stain. The mitochondria appear as bright red masses against the blue background of the myofibers, which led to the term "ragged red fibers" (RRF)
- 17. Electron microscopymay show abnormal mitochondria with increased size and abnormal cristae. Muscle respiratory chain enzymology o Performed on frozen skeletal muscle tissue. o The activities of the enzyme complexes involved in making adenosine triphosphate (ATP) are measured and expressed relative to citrate synthase, a marker enzyme.
- 18. Carried outon genomic DNA extracted from blood (suspected nuclear DNA mutations and some mtDNA mutations) or on genomic DNA extracted from muscle. However, even patients who have a known pathogenic mtDNA mutation may be asymptomatic depending on the percentage load of mutant mtDNA.
- 19. I. Symptomatic Treatment IncludingRespiratory care, Seizures control, CVS assessment and DM screening. II. Exercise Beneficial in mitochondrial disorders. Aerobic exercise increases peak work, oxidative capacity, and mitochondrial volume. Aerobic exercise can prevent muscle deconditioning and decrease exercise intolerance.
- 20. III. Pharmacological Therapy No proven Effective Therapy. A. Respiratory chain cofactors Succinate, riboflavin, thiamine, and coenzyme Q10 participate as cofactors in the electron transport chain enzymes. Supplementation is thought to enhance the activity of these enzymes when they are deficient. B. Antioxidants Mitochondrial diseases in general result in an increase in oxidative stress and higher levels of reactive oxygen species. This may cause damage to the cell membrane through lipid peroxidation. C. Correcting secondary biochemical deficits Levels of carnitine, creatine, and folate are decreased in patients with mitochondrial disorders, although the exact mechanisms are unclear. They are often given as part of a "mitochondrial cocktail" to patients.
- 21. 1. Mitochondrial DisordersOverview, 2010, Patrick F Chinnery 2. Diagnosis and management of patients with mitochondrial disease,2011, Andre Mattman et al. 3. Primer on mitochondrial disease: Biochemistry, genetics, and epidemiology, 2011, Sandra Sirrs et al. 4. Mitochondrial myopathies: Clinical features and diagnosis, Uptodate. 5. Mitochondrial myopathies: Treatment, Uptodate.