TY  - JOUR
AU  - Klopstock, Thomas
AU  - Priglinger, Claudia
AU  - Yilmaz, Ali
AU  - Kornblum, Cornelia
AU  - Distelmaier, Felix
AU  - Prokisch, Holger
TI  - Mitochondrial Disorders.
JO  - Deutsches Ärzteblatt international
VL  - 118
IS  - 44
SN  - 1866-0452
CY  - Köln
PB  - Dt. Ärzte-Verl.
M1  - DZNE-2022-00157
SP  - 741-748
PY  - 2021
AB  - Mitochondrial disorders are among the most common heritable diseases, with an overall lifetime risk of approximately one in 1500. Nonetheless, their diagnosis is often missed because of their extreme phenotypic and genotypic heterogeneity.This review is based on publications retrieved by a selective literature search on the clinical features, genetics, pathogenesis, diagnosis, and treatment of mitochondrial diseases.Pathogenic defects of energy metabolism have been described to date in over 400 genes. Only a small number of these genes lie in the mitochondrial DNA; the corresponding diseases are either maternally inherited or of sporadic distribution. The remaining disease-associated genes are coded in nuclear DNA and cause diseases that are inherited according to Mendelian rules, mostly autosomal recessive. The most severely involved organs are generally those with the highest energy requirements, including the brain, the sensory epithelia, and the extraocular, cardiac, and skeletal musculature. Typical manifestations include epileptic seizures, stroke-like episodes, hearing loss, retinopathy, external ophthalmoparesis, exercise intolerance, and diabetes mellitus. More than two manifestations of these types should arouse suspicion of a disease of energy metabolism. The severity of mitochondrial disorders ranges from very severe disease, already evident in childhood, to relatively mild disease arising in late adulthood. The diagnosis is usually confirmed with molecular-genetic methods. Symptomatic treatment can improve patients' quality of life. The only disease-modifying treatment that has been approved to date is idebenone for the treatment of Leber hereditary optic neuropathy. Intravitreal gene therapy has also been developed for the treatment of this disease; its approval by the European Medicines Agency is pending.Patients with mitochondrial diseases have highly varied manifestations and can thus present to physicians in practically any branch of medicine. A correct diagnosis is the prerequisite for genetic counseling and for the initiation of personalized treatment.
KW  - Adult
KW  - DNA, Mitochondrial: genetics
KW  - Humans
KW  - Mitochondrial Diseases: diagnosis
KW  - Mitochondrial Diseases: genetics
KW  - Mitochondrial Diseases: therapy
KW  - Optic Atrophy, Hereditary, Leber
KW  - Quality of Life
KW  - DNA, Mitochondrial (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:34158150
C2  - pmc:PMC8830351
DO  - DOI:10.3238/arztebl.m2021.0251
UR  - https://pub.dzne.de/record/163395
ER  -