Red flag neurologic symptoms Stroke Basal ganglia lesions Encephalopathy- hepatopathy Epilepsy Cognitive decline Ataxia Ocular signs (optic atrophy,retinal pigmentary degeneration,ptosis and ophthalmoparesis) Sensorineural hearing loss

A 4 y. old boy with abnormal gait since few months ago A 4 y. old boy with abnormal gait since few months ago. He had spasticity with UMN signs in lower limb.

Skin biopsy , Fibroblast culture and “Respiratory Chain” testing showed a Complex 4 deficiency.

A 3 y. 8 m. old boy with hearing loss since. And candidate for CI A 3 y. 8 m. old boy with hearing loss since ?? And candidate for CI .Has spastic gait since one month ago . He is the product of consanguineous marriage

4 y. old girl with Hx. Of seizure dis. After a febrile illness 4 m. ago. She was doing well before that. Despite appropriate treatment of ADEM she had decline in motor and cognitive function. CSF was normal. W/U for MS negative. Optic atrophy in ophtalmologic exam. CSF lactate was significantly increased.

11 y. old boy with hx. Of ataxia and seizure since fifth y. of age 11 y. old boy with hx. Of ataxia and seizure since fifth y. of age . Had motor and cognitive regression since then and several PICU admission for status epilepticus. Now he is bedridden. Diagnosis of SSPE was made

16 m. old boy with hx. of Seizure since 3 months ago , multiple type , refractory and so intense leading to multiple PICU admission .

After starting VPA for seizure LFT rised up and he developed hepatic failure.

Mitochondrial Disorder Mitochondrial DNA mutation (mt DNA) Nuclear DNA mutation (n DNA)

Mitochondrial DNA mutation (mt DNA) are the earliest identified (syndromic)

1000 nuclear genes are involved in mitochondrial function.

Classic clinical MRC disorder phenotypes, ragged red fibers, and mtDNA mutations are rare in youngsters.

Finding a mutation is difficult in most children with a mitochondrial disorder. Ninety percent carry a nuclear DNA mutation in one of the 1000 proteins involved in normal functioning of the mitochondria, and most of these mutations have yet to be elucidated. So Enzyme analysis is very important: Polarographic and Spectrophotometric Assays in muscle biopsy.other tissu?