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Biochemical Pathways Fatty acid oxidation Oxidative phosphorylation Mitochondria General features Mitochondrial DNA (mtDNA) General Features Mutations Nuclear encoded proteins General Features Mutations Mitochondrial disorders Biochemical classification Clinical syndromes Evaluation Clinical Signs Laboratory General mechanisms Mutation types Mitochondrial Nuclear encoded proteins Functional defects Pathology Histology Ultrastructure |
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Differences from Nuclear DNA Inheritance mtDNA variation Mutations Pathogenic mechanisms Structure Transcription & translation |
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TCA cycle![]() |
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![]() Intense SDH staining of a muscle fiber with mitochondrial proliferation |
Also see: Neuro-Gastro-intestinal variants |
Sporadic Mitochondrial DNA changes Single mtDNA deletion, or Multiple mtDNA deletions Kearns-Sayre: Single large mtDNA deletion PEO + Proximal myopathy Sensory ataxic neuropathy ? Immune (HyperThyroid) Dominant Mitochondrial DNA changes Multiple mtDNA deletions Twinkle: 10q23 ANT1: 4q35 POLG: 15q25 POLG2: 17q Hypogonadism Recessive Mitochondrial DNA changes mtDNA depletion, or Multiple mtDNA deletions MNGIE: Thymidine phosphorylase; 22q13 POLG: 15q25 PEO + Cardiomyopathy PEO + Myopathy & Parkinsonism Sensory neuropathy Also see: Congenital ophthalmoplegia |
Maternal Mitochondrial DNA changes mtDNA point mutations May be sporadic tRNALeu(UUR) MELAS PEO tRNALeu(CUN) tRNAAsn tRNAGln: PEO-plus tRNAAla: PEO-plus tRNATyr: PEO-plus tRNALys: PEO-plus tRNAIle ![]() |
Autosomal Dominant PEO: Clinical features | |||
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![]() Triple furrowed tongue
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Twinkle: 10q23 ANT1: 4q35 POLG: 15q25 POLG2: 17q Hypogonadism |
Autosomal Dominant Autosomal Recessive Maternal Sporadic Myoglobinuria |
Cytochrome c Oxidase: Subunit 2 Mitochondrial tRNA mutations Sporadic myopathies |
Adult onset Anemia Ataxia Cardiac Deafness Diabetes Infantile encephalopathies Multiple symmetric lipomatosis Optic atrophy |
Mitochondrial DNA mutations mtRNA Other Nuclear DNA mutations |
Autosomal Recessive inheritance, Syndromic Wolfram (DIDMOAD): WFS1; WFS2 Deafness-Dystonia syndrome Maternal (mitochondrial) inheritance Non-syndromic Syndromic Sporadic syndromic |
Clinical features Lab features Types Mitochondrial mtDNA deletions Nuclear mutations |
Causes of Leigh-like Syndrome3 | |
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Defect | Frequency (%) |
mtDNA mutation | 18 |
PDHC | 10 |
Complex I | 19 |
COX deficiency | 14 |
Complex II + Other | 39 |
Mitochondrial mutations MILS (LS): ATPase 6 MTND5 MTND6 tRNAs COX III mtDNA deletions (LS) Nuclear mutations Complex I NDUFA11: 19 NDUFS3 (LS): 11p11 NDUFS4 (LS & IE): 5q11 NDUFS7 (LS): 19p13 NDUFS8 (LS): 11q13 NDUFV1 (LS): 11q13 C8orf38 (LS): 8 Complex II SDHA (LS): 5p15 Complex III BCS1L (LS): 2q33 Complex IV LRPPRC (LS): 2p16 Surfeit-1 (LS): 9q34 SCO2 (IE): 22q13 Pyruvate metabolism Pyruvate carboxylase (LS): 11q13 Pyruvate decarboxylase (LS) Pyruvate dehydrogenase Pyruvate dehydrogenase E1-α (LS): Xp22 Dihydrolipoyl transacetylase E2 (IE): DLAT; 11q23 Lipoamide dehydrogenase E3 (LS): 7q31 Protein X Phospho-E phosphatase Infantile encephalopathies: Other |
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