Klinische FragestellungEnzephalopathie, mitochondriale; Differentialdiagnose

NGS +

[[Sanger]]

Mitochondriale Erkrankungen sind klinisch, biochemisch und genetisch heterogen. Gemeinsames Kennzeichen sind Störungen im Bereich mitochondrial lokalisierter Stoffwechselwege. Es handelt sich überwiegend um Multisystemerkrankungen, bei denen die Skelettmuskulatur häufig, jedoch nicht immer beteiligt ist. Das klinische Spektrum reicht von schweren Multiorganaffektionen im frühen Kindesalter bis zu milden monosymptomatischen Verläufen im Erwachsenenalter. Selbst unspezifisch imponierende Beschwerden insbesondere der Muskulatur oder isolierte Symptome des zentralen Nervensystems wie Epilepsien können Ausdruck mitochondrialer Erkrankungen des Erwachsenenalters sein. Mitochondriopathien können sich im Kindes-, Jugend- oder Erwachsenenalter erstmanifestieren, wobei der Beginn interindividuell sehr variabel sein kann. So können sich typische Syndrome des Kindesalters auch erst im zweiten Lebensjahrzehnt oder deutlich später zeigen. Ursache mitochondrialer Funktionsstörungen können Mutationen nukleärer Gene (aktuell >350 Gene) oder des mitochondrialen Genoms, der mtDNA, sein. Der zu Grunde liegende genetische Defekt lässt sich jedoch trotz aller Fortschritte noch nicht bei jedem Patienten nachweisen. Mitochondriale Erkrankungen können nach dem klinischen Syndrom, dem zu Grunde liegenden biochemischen oder dem genetischen Defekt klassifiziert werden. Das hier verwendete Panel enthält Gene, die insbesondere mit mitochondrialen Enzephalopathien assoziiert sind.

Literatur:

AWMF-Leitlinie „Mitochondriale Erkrankungen“; 030-049l_S1_Mitochondriale-Erkrankungen_2021-02_01.pdf

• Allelic: Cataract 38, AR (AGK)
• Allelic: Charcot-Marie-Tooth disease, axonal, type 2A2A (MFN2)
• Allelic: Charcot-Marie-Tooth disease, axonal, type 2A2B (MFN2)
• Allelic: Charcot-Marie-Tooth disease, axonal, type 2EE (MPV17)
• Allelic: Glaucoma, normal tension, susceptibility to (OPA1)
• Allelic: Hereditary motor + sensory neuropathy VIA (MFN2)
• Allelic: Mitochondrial DNA depletion syndrome 12A, cardiomyopathic type, AD (SLC25A4)
• Allelic: Mitochondrial DNA depletion syndrome 12B, cardiomyopathic type, AR (SLC25A4)
• Allelic: Mitochondrial DNA depletion syndrome 2, myopathic type (TK2)
• Allelic: Multiple system atrophy, susceptibility to (COQ2)
• Allelic: Optic atrophy 1 (OPA1)
• Allelic: Perrault syndrome 5 (TWNK)
• Allelic: Portal hypertension, noncirrhotic, 1 (DGUOK)
• Ataxia, early-onset, with oculomotor apraxia + hypoalbuminemia (APTX)
• Behr syndrome (OPA1)
• Bjornstad syndrome (BCS1L)
• Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1 (SCO2)
• Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2 (COX15)
• Cardiomyopathy, dilated, 1GG (SDHA)
• 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)
• Combined oxidative phosphorylation deficiency 15 (MTFMT)
• Dihydrolipoamide dehydrogenase deficiency (DLD)
• Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission included
• GABA-transaminase deficiency (ABAT)
• GRACILE syndrome (BCS1L)
• Glutaric acidemia IIC (ETFDH)
• Leber hereditary optic neuropathy, AR (DNAJC30)
• Leigh syndrome (BCS1L, COX10, SDHA)
• Leigh syndrome due to cytochrome c oxidase deficiency (COX15)
• Leigh syndrome, due to COX IV deficiency (SURF1)
• Mitochondrial DNA depletion syndrome 11 (MGME1)
• Mitochondrial DNA depletion syndrome 11 (POLG2)
• Mitochondrial DNA depletion syndrome 13, encephalomyopathic type (FBXL4)
• Mitochondrial DNA depletion syndrome 14, encephalocardiomyopathic type (OPA1)
• Mitochondrial DNA depletion syndrome 15, hepatocerebral type (TFAM)
• Mitochondrial DNA depletion syndrome 18 (SLC25A21)
• 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 6, hepatocerebral type (MPV17)
• Mitochondrial DNA depletion syndrome 7, hepatocerebral type (TWNK)
• Mitochondrial DNA depletion syndrome 8A, encephalomyopathic type with renal tubulopathy (RRM21B)
• Mitochondrial DNA depletion syndrome 8B, MNGIE type (RRM21B)
• Mitochondrial DNA depletion syndrome 9, encephalomyopathic type with methylmalonic aciduria (SUCLG1)
• Mitochondrial complex I deficiency, nuclear type 1 (NDUFS4)
• Mitochondrial complex I deficiency, nuclear type 13 (NDUFA2)
• Mitochondrial complex I deficiency, nuclear type 16 (NDUFAF5)
• Mitochondrial complex I deficiency, nuclear type 17 (NDUFAF6)
• Mitochondrial complex I deficiency, nuclear type 2 (NDUFS8)
• Mitochondrial complex I deficiency, nuclear type 22 (NDUFA10)
• Mitochondrial complex I deficiency, nuclear type 23 (NDUFA12)
• 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 31 (NDUFS1)
• Mitochondrial complex I deficiency, nuclear type 8 (NDUFS3)
• Mitochondrial complex III deficiency, nuclear type 1 (BCS1L)
• Mitochondrial complex IV deficiency (COX10)
• Mitochondrial complex IV deficiency (PDHA1)
• Mitochondrial complex IV deficiency (TACO1)
• Mitochondrial recessive ataxia syndrome, includes SANDO + SCAE (POLG)
• Mitochondrial respiratory chain complex II deficiency (SDHA)
• Multiple mitochondrial dysfunctions syndrome 1 (NFU1)
• Multiple mitochondrial dysfunctions syndrome 2 with hyperglycinemia (BOLA3)
• Multiple mitochondrial dysfunctions syndrome 3 (IBA57)
• Multiple mitochondrial dysfunctions syndrome 4 (ISCA2)
• Myopathy, mitochondrial progressive, with congenital cataract + developmental delay (GFER)
• Nephrotic syndrome, type 9 (COQ8B)
• Optic atrophy 12 (AFG3L2)
• Optic atrophy plus syndrome (OPA1)
• Paragangliomas 5 (SDHA)
• Progressive external ophthalmoplegia with mitochondrial DNA deletions, 3 (TWNK)
• Progressive external ophthalmoplegia with mitochondrial DNA deletions, AD 2 (SLC25A4)
• Progressive external ophthalmoplegia with mitochondrial DNA deletions, AD 5 (RRM2B)
• Progressive external ophthalmoplegia with mitochondrial DNA deletions, AD 6 (DNA2)
• Progressive external ophthalmoplegia with mitochondrial DNA deletions, AR 2 (RNASEH1)
• Progressive external ophthalmoplegia with mitochondrial DNA deletions, AR 3 (TK2)
• Progressive external ophthalmoplegia with mitochondrial DNA deletions, AR 4 (DGUOK)
• Progressive external ophthalmoplegia, AD 1 (POLG)
• Progressive external ophthalmoplegia, AR1 (POLG)
• Pyruvate dehydrogenase E1-alpha deficiency (PDHA1)
• Seckel syndrome 8 (DNA2)
• Sengers syndrome (AGK)
• Spastic ataxia 5, AR (AFG3L2)
• Spastic paraplegia 7, AR (SPG7)
• Spinocerebellar ataxia 28 (AFG3L2)
• Spinocerebellar ataxia, AR 10 (ANO10)