9 th Medical Genetic Course Center for Biomedical Researh (CEBIOR), Diponegoro University, Semarang, Indonesia In collaboration with Radboud University of Nijemegen, Medical Centre (RUNMC), The Netherlands

History of Illness Symptoms: Fever Headache Confusion Partial seizures with secondary generalization Family history Antecedents: Deafness & DM in maternal lineage Physical examination Right parieto-temporal syndrome Left hemiparesis Hypoaesthesia Left homonymous hemianopia Topographical disorientation Sensorineural deafness of acute onset Male 38 yrs old, right handed Antiviral treatment (acyclovir) was given

06/11/2015Genetic Counseling, FMDU3 Family history: Several antecedents has deafness & DM in maternal lineage

Additional Examination CT Scan – Low density area at parietal lobe MRI – Cortical and subcortical hyperintensities unilaterally at right parietal and temporo- occipital lobes – Diffuse atrophy of the cerebellar cortex LCS – Looks clear yet plasma and LCS lactic acid are elevated Muscle biopsy – Many red ragged fibers (RRF), mostly positive for COX activity Explains right parieto-temporal syndrome: Left hemiparesis, Hypoaesthesia, Left homonymous hemianopia, Topographical disorientation, SNHL Ictal Record – High amplitude, rhytmic sharp waves at right parieto- temporo-occipital region  high amplitude, slow waves background Partial seizures with secondary generalization

Differential Diagnosis MELAS (Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like syndrome) MERRF (Myoclonic epilepsy and ragged-red fibers) Kearns Sayre Syndrome

06/11/2015Genetic Counseling, FMDU6 N Engl J Med 2003;348:

Further Investigations PCR-RFLP to find out the mtDNA mutation from blood sample J Korean Med Sci 2002; 17:

Further Investigations PCR-RFLP to find out the mtDNA mutation from blood sample J Korean Med Sci 2002; 17:

Final Diagnosis PCR-RFLP to find out the mtDNA mutation from blood sample J Korean Med Sci 2002; 17: Final Diagnosis  MELAS

Therapy  No definite drug major negative effect of neuropathy in MELAS Dichloroacetate (DCA) Formerly for Parkinson disease, large phase III trial is on its way Coenzyme Q10 Formerly for Friedreich ataxia, still in clinical trial for mitochondrial disorders Idebenone Molecular Genetics and Metabolism 2010;99:246–55 Said to be promising in the future for lowering episodes of stroke L-Arginine Mitochondrion 2007;7:133–9

Genetic Counseling  Nightmare Recurrence risk  finding threshold???  general threshold??? 06/11/2015Genetic Counseling, FMDU11

Genetic Counseling  Nightmare Reccurence risk  finding threshold???  Quantitative RT-PCR 06/11/2015Genetic Counseling, FMDU12 Clinica Chimica Acta 390 (2008) 126–133 Clinical Chemistry 2004;50(6):

9 th Medical Genetic Course Center for Biomedical Researh (CEBIOR), Diponegoro University, Semarang, Indonesia In collaboration with Radboud University of Nijemegen, Medical Centre (RUNMC), The Netherlands Thank You Feedbacks are expected 06/11/2015Genetic Counseling, FMDU13