All are selected mitochondrial disease EXCEPT
(Spino- cerebellar ataxia) (400-HI7th)* Spino-cerebellar ataxia is a selected trinucleotide repeat disordersSelected trinucleotide repeat disorders are - X- chromosomal spinobulbar muscular atrophy (SBMA, fragile-x syndrome, Dystrophia myotonica, Huntington disease spino-cerebellar ataxia Dentorubral pallido luysiane atrophy (DRPLA), Friedreich ataxiaSelected Mitochondrial Diseases (400-H17th)* MELAS syndrome: mitochondrial myopathy with encephalopathy, lactic acidosis and stroke* Leber's optic atrophy: hereditary optical neuropathy* Kearns-sayre syndrome (KSS): ophthalmoplegia, pigmental degeneration of the retina, cardiomyopathy* MERRF syndrome- myoclonic epilepsy and ragged- red fibers* Neurogenic muscular weakness with ataxia and retinitis pigmentosa (NARP)* Porgressive external ophthalmoplegia (CEOP)* Pearson syndrome (PEAR) bone marrow and pancreatic failure* Autosomal dominant Inherited mitochondrial myopathy with mitochondrial deletion (ADMIMY)* Somatic mutations in cytochrome b gene exercise intolerance, lactic acidosis, complex III deficiency muscle pain ragged- red fibers* Inherited mitochondrial disorders are transmitted in a matrilineal fashion; all children from an affected mother will inherit the disease but it will not be transmitted from an affected father to his children* Mitochondrial disorders have clinical manifestations - 3groups- Chronic progressive external ophthalmoplegia (CPEO)- Skeletal muscle - CNS syndrome- Pure myopathy simulating muscular dystrophy or metabolic myopathyMitochondrial DNA Depletion Myopathy (2691 -H17th)- Usually presents in neonatal period with weakness hypotonia and delayed motor milestones- Proximal muscle weakness- Seizure and cardiomyopathy- CK levels reaches levels of 20 to30 times normal- Resting lactate normal to mildely elevated- EMG is myopathy, reggedrcd fibres are seen on muscle biopsy- The mt DNA depletion syndrome is inherited as an autosomal recessive (AR)- Mutations- TK2 gene on chromosome 16q 22 encoding thyidine kinase-2- No specific treatment
Leber's optic atrophy
Kearns- sayre syndrome
Progressive external ophthalmoplegia
Spino-cerebellar ataxia
Genetics