Klinische FragestellungMyopathie, mitochondriale, incl. CPEO; Differentialdiagnose

NGS +

[[Sanger]]

Mitochondriale Myopathien sind eine Gruppe von fortschreitenden Muskelerkrankungen, die in erster Linie durch die Beeinträchtigung der oxidativen Phosphorylierung verursacht werden. Die Myopathie ist aufgrund des hohen zellulären Energiebedarfs der Skelettmuskulatur eine der häufigsten Manifestationen von mitochondrialen Erkrankungen im Erwachsenenalter. Allerdings zeigen Patienten mit mitochondrialer Myopathie oft auch eine Dysfunktion in mehreren Organsystemen, was zur großen Variabilität im klinischen Phänotyp und der Prognose führt. Diese Erkrankungen sind daher praktisch immer multisystemische Störungen, die sich unter anderem mit einer Vielzahl von neurologischen, hepatischen und gastrointestinalen Symptomen präsentieren. Die Myopathie führt oft zu Belastungsintoleranz, Krämpfen und Müdigkeit. Proximale Myopathie ist die häufigste Form, der Grad der Schwäche ist variabel, die Patienten häufig schnell ermüdbar. Bei einigen Patienten ist auch die Atemmuskulatur betroffen, so dass apparative Beatmung erforderlich wird. Chronisch progressive externe Ophthalmoplegie ist eine häufige Erscheinung bei Patienten mit mitochondrialer Erkrankung und ist häufig mit proximaler Myopathie verbunden. Darüber hinaus sind belastungsinduzierte Muskelschmerzen ein häufiges Merkmal, selten Rhabdomyolyse, während Müdigkeit das am häufigsten von den Patienten berichtete Symptom ist. Die Erkrankungen aus dieser Gruppe werden anhand praktisch unübersehbar vieler Kerngenom-Mutationen zumeist autosomal rezessiv, seltener autosomal dominant und nur ausnahmsweise X-chromosomal vererbt. Die molekulargenetische Ausbeute ist bei mitochondrialen Leiden nur sehr schwer und mit erheblichen Einschränkungen zu erfassen. Ein negatives molekulargenetisches Ergebnis stellt keinen Ausschluss der klinischen Diagnose dar.

Referenz: https://www.ncbi.nlm.nih.gov/books/NBK1224/

• Alias: Combined oxidative phosphorylation deficiency
• Alias: Complex multisystem presentation
• Alias: Disorders of mitochondrial DNA maintenance and integrity
• Alias: Disorders of mitochondrial apoptosis
• Alias: Disorders of mitochondrial lipid metabolism
• Alias: Disorders of ubiquinone metabolism and biosynthesis
• Alias: Mitochondrial disorders
• Alias: Mitochondrial myopathy
• Alias: Multiple respiratory chain complex deficiencies
• Allelic: CPT II deficiency, lethal neonatal (CPT2)
• Allelic: Charcot-Marie-Tooth disease, axonal type 2M (DNM2)
• Allelic: Charcot-Marie-Tooth disease, dominant intermediate B (DNM2)
• Allelic: Charcot-Marie-Tooth disease, type 4K (SURF1)
• Allelic: Deafness, AR 70 (PNPT1)
• Allelic: Encephalopathy, acute, infection-induced, 4, susceptibility to (CPT2)
• Allelic: Fanconi renotubular syndrome 5 (NDUFAF6)
• Allelic: Fazio-Londe disease (SLC52A3)
• Allelic: Frontotemporal dementia and/or amyotrophic lateral sclerosis 2 (CHCHD10)
• Allelic: Gastrointestinal stromal tumor (SDHB, SDHC)
• Allelic: Hyperinsulinemic hypoglycemia, familial, 4 (HADH)
• Allelic: Microcephaly, growth restriction + increased sister chromatid exchange 2 (TOP3A)
• Allelic: Myopia 6 (SCO2)
• Allelic: Perrault syndrome 5 (TWNK)
• Allelic: Pheochromocytoma (SDHB, SDHD)
• Allelic: Spastic paraplegia 77, AR (FARS2)
• 3-hydroxyacyl-CoA dehydrogenase deficiency (HADH)
• 3-methylglutaconic aciduria with deafness, encephalopathy + Leigh-like syndrome (SERAC1)
• Allelic: Charcot-Marie-Tooth disease, axonal, type 2EE (MPV17)
• Barth syndrome (TAFFAZIN)
• Bjornstad syndrome, GRACILE syndrome (BCS1L)
• Brown-Vialetto-Van Laere syndrome 1 (SLC52A3)
• Brown-Vialetto-Van Laere syndrome 2 (SLC52A2)
• CPT II deficiency, infantile (CPT2)
• CPT II deficiency, myopathic, stress-induced (CPT2)
• CPT deficiency, hepatic, type IA (CPT1A)
• Centronuclear myopathy 1 (DNM2)
• Chanarin-Dorfman syndrome (ABHD5)
• Charcot-Marie-Tooth disease, axonal, type 2A2A (MFN2)
• Charcot-Marie-Tooth disease, axonal, type 2A2B (MFN2)
• Coenzyme Q10 deficiency, primary, 1 (COQ2)
• Coenzyme Q10 deficiency, primary, 2 (PDSS1)
• Coenzyme Q10 deficiency, primary, 3 (PDSS2)
• Coenzyme Q10 deficiency, primary, 4 (COQ8A)
• Coenzyme Q10 deficiency, primary, 5 (COQ9)
• Coenzyme Q10 deficiency, primary, 6 (COQ6)
• Coenzyme Q10 deficiency, primary, 7 (COQ4)
• Coenzyme Q10 deficiency, primary, 8 (COQ7)
• Coenzyme Q10 deficiency, primary, 9 (COQ5)
• Combined oxidative phosphorylation deficiency 1 (GFM1)
• Combined oxidative phosphorylation deficiency 12 (EARS2)
• Combined oxidative phosphorylation deficiency 13 (PNPT1)
• Combined oxidative phosphorylation deficiency 14 (FARS2)
• Combined oxidative phosphorylation deficiency 15 (MTFMT)
• Combined oxidative phosphorylation deficiency 20 (VARS2)
• Combined oxidative phosphorylation deficiency 3 (TSFM)
• Combined oxidative phosphorylation deficiency 40 (QRSL1)
• Combined oxidative phosphorylation deficiency 44 (FASTKD2)
• Ethylmalonic encephalopathy (ETHE1)
• Exocrine pancreatic insufficiency, dyserythropoietic anemia + calvarial hyperostosis (COX4I2)
• GABA-transaminase deficiency (ABAT)
• Glutaric acidemia IIC (ETFDH)
• Hereditary motor and sensory neuropathy VIA (MFN2)
• Lacticacidemia due to PDX1 deficiency (PDHX)
• Leigh syndrome (BCS1L, SDHA)
• Lethal congenital contracture syndrome 5 (DNM2)
• Lipid storage myopathy due to flavin adenine dinucleotide synthetase deficiency (FLAD1)
• Lipoyltransferase 1 deficiency (IARS2)
• Lipoyltransferase 1 deficiency (LIPT1)
• Liver failure, transient infantile (TRMU)
• Metabolic crises, recurrent, variable encephalomyopathic features, neurologic regression (SLC25A42)
• Mitochondrial DNA depletion syndrome (AGK)
• Mitochondrial DNA depletion syndrome 1, MNGIE type (TYMP)
• Mitochondrial DNA depletion syndrome 11 (MGME1)
• Mitochondrial DNA depletion syndrome 13, encephalomyopathic type (FBXL4)
• Mitochondrial DNA depletion syndrome 16, hepatic type (POLG2)
• Mitochondrial DNA depletion syndrome 2, myopathic type (TK2)
• Mitochondrial DNA depletion syndrome 3, hepatocerebral type (DGUOK)
• Mitochondrial DNA depletion syndrome 4A, Alpers type (POLG)
• Mitochondrial DNA depletion syndrome 4B, MNGIE type (POLG)
• Mitochondrial DNA depletion syndrome 5, encephalomyopathic +/- methylmalonic aciduria (SUCLA2)
• Mitochondrial DNA depletion syndrome 6, hepatocerebral type (MPV17)
• Mitochondrial DNA depletion syndrome 7, hepatocerebral type (TWNK)
• Mitochondrial DNA depletion syndrome 8A, encephalomyopathic type with renal tubulopathy (RRM2B)
• Mitochondrial DNA depletion syndrome 8B, MNGIE type (RRM2B)
• Mitochondrial DNA depletion syndrome 9, encephalomyopathic type + methylmalonic aciduria (SUCLG1)
• Mitochondrial complex I deficiency, nuclear type 1 (NDUFS4)
• Mitochondrial complex I deficiency, nuclear type 10 (NDUFAF2)
• Mitochondrial complex I deficiency, nuclear type 11 (MDUFAF1)
• Mitochondrial complex I deficiency, nuclear type 12 (NDUFA1)
• Mitochondrial complex I deficiency, nuclear type 13 (NDUFA2)
• Mitochondrial complex I deficiency, nuclear type 14 (NDUFA11)
• Mitochondrial complex I deficiency, nuclear type 15 (MDUFAF4)
• Mitochondrial complex I deficiency, nuclear type 16 (NDUFAF5)
• Mitochondrial complex I deficiency, nuclear type 17 (NDUFAF6)
• Mitochondrial complex I deficiency, nuclear type 18 (MDUFAF3)
• Mitochondrial complex I deficiency, nuclear type 19 (FOXRED1)
• Mitochondrial complex I deficiency, nuclear type 2 (NDUFS8)
• Mitochondrial complex I deficiency, nuclear type 20 (ACAD9)
• Mitochondrial complex I deficiency, nuclear type 22 (NDUFA10)
• Mitochondrial complex I deficiency, nuclear type 26 (NDUFA9)
• Mitochondrial complex I deficiency, nuclear type 27 (MTFMT)
• Mitochondrial complex I deficiency, nuclear type 3 (NDUFS7)
• Mitochondrial complex I deficiency, nuclear type 4 (NDUFV1)
• Mitochondrial complex I deficiency, nuclear type 5 (NDUFS1)
• Mitochondrial complex I deficiency, nuclear type 6 (NDUFS2)
• Mitochondrial complex I deficiency, nuclear type 8 (NDUFS3)
• Mitochondrial complex I deficiency, nuclear type 9 (MDUFS6)
• Mitochondrial complex II deficiency, nuclear type 2 (SDHAF1)
• Mitochondrial complex II deficiency, nuclear type 3 (SDHD)
• Mitochondrial complex II deficiency, nuclear type 4 (SDHB)
• Mitochondrial complex III deficiency, nuclear type 2 (TTC19)
• Mitochondrial complex III deficiency, nuclear type 3 (UQCRB)
• Mitochondrial complex III deficiency, nuclear type 4 (UQCRQ)
• Mitochondrial complex IV deficiency (COX20)
• Mitochondrial complex IV deficiency, nuclear type 1 (SURF1)
• Mitochondrial complex IV deficiency, nuclear type 13 (COA6)
• Mitochondrial complex IV deficiency, nuclear type 17 (COA8)
• Mitochondrial complex IV deficiency, nuclear type 2 (SCO2)
• Mitochondrial complex IV deficiency, nuclear type 21 (NDUFA4)
• Mitochondrial complex IV deficiency, nuclear type 3 (COX10)
• Mitochondrial complex IV deficiency, nuclear type 4 (SCO1)
• Mitochondrial complex IV deficiency, nuclear type 5, French-Canadian (LRPPRC)
• Mitochondrial complex IV deficiency, nuclear type 6 (COX15)
• Mitochondrial complex IV deficiency, nuclear type 7 (COX6B1)
• Mitochondrial complex IV deficiency, nuclear type 8 (TACO1)
• Mitochondrial complex V, ATP synthase deficiency, nuclear type 1 (ATPAF2)
• Mitochondrial complex V, ATP synthase deficiency, nuclear type 2 (TMEM70)
• Mitochondrial complex V, ATP synthase deficiency, nuclear type 3 (ATP5E)
• Mitochondrial complex V, ATP synthase deficiency, nuclear type 4 (ATP5F1A syn. ATP5A)
• Mitochondrial encephalomyopathy w/combined respiratory chain deficiency (AIF1)
• Mitochondrial myopathy with lactic acidosis (PET100)
• Mitochondrial myopathy with lactic acidosis (PNPLA8)
• Mitochondrial myopathy, episodic, optic atrophy + reversible leukoencephalopathy (FDX2 syn. FDX1L)
• Mitochondrial phosphate carrier deficiency (SLC25A3)
• Mitochondrial recessive ataxia syndrome [includes SANDO + SCAE] (POLG)
• Mitochondrial respiratory chain complex II deficiency (SDHA)
• Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency (ECHS1)
• Multiple mitochondrial dysfunctions syndrome 3 (IBA57)
• Multiple system atrophy, susceptibility to (COQ2)
• Myopathy with extrapyramidal signs (MICU1)
• Myopathy with lactic acidosis, hereditary (ISCU)
• Myopathy, isolated mitochondrial, AD (CHCHD10)
• Myopathy, lactic acidosis + sideroblastic anemia 1 (PUS1)
• Myopathy, lactic acidosis + sideroblastic anemia 2 (YARS2)
• Myopathy, mitochondrial + ataxia (MSTO1)
• Myopathy, mitochondrial progressive, with congenital cataract + developmental delay (GFER)
• Myopathy, vacuolar, with CASQ1 aggregates (CASQ1)
• Neutral lipid storage disease with myopathy (PNPLA2)
• Paraganglioma + gastric stromal sarcoma (SDHB, SDHC, SDHD)
• Paragangliomas 1, with/-out deafness (SDHD)
• Paragangliomas 2 (SDHAF2)
• Paragangliomas 3 (SDHC)
• Paragangliomas 4 (SDHB)
• Progressive external ophthalmoplegia with mitochondrial DNA deletions, AD 3 (TWNK)
• Progressive external ophthalmoplegia with mitochondrial DNA deletions, AR 2 (RNASEH1)
• Progressive external ophthalmoplegia with mitochondrial DNA deletions, AR 4 (DGUOK, POLG2)
• Progressive external ophthalmoplegia with mitochondrial DNA deletions, AR 5 (TOP3A)
• Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3 (TK2)
• Progressive external ophthalmoplegia, AD 1 (POLG)
• Pyruvate dehydrogenase E1-alpha deficiency (PDHA1)
• Pyruvate dehydrogenase E1-beta deficiency (PDHB)
• Riboflavin deficiency (SLC52A1)
• Sengers syndrome (AGK)
• Spastic ataxia 5, AR (AFG3L2)
• Spastic paraplegia 7, AR (SPG7)
• Spinal muscular atrophy, Jokela type (CHCHD10)
• Thiamine metabolism dysfunction syndrome 2, biotin-/thiamine-resp. encephalopathy type 2 (SLC19A3)
• Thiamine metabolism dysfunction syndrome 5, episodic encephalopathy type (TPK1)