This document discusses MELAS (Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like Episodes), a mitochondrial disease. MELAS is most commonly caused by the A3243G mutation and is maternally inherited. It is characterized by stroke-like episodes typically beginning in the teenage years, as well as other symptoms like diabetes, deafness, and cognitive impairment. Brain imaging during episodes shows cortical lesions. Muscle biopsies may reveal abnormal mitochondria clustering in blood vessels. There is currently no cure, but certain treatments can help manage symptoms.

1. MELAS and ITS SISTERS Prof. Dr. Saad S Al Ani Senior Pediatric Consultant Head of Pediatric Department Khorfakkan Hospital Sharjah ,UAE [email_address]

9. WHAT IS THE DIAGNOSIS ?

16. WHAT IS THE DIAGNOSIS ?

17. A mitochondrial cytopathy

22. Intermediary Energy Metabolism ATP Pool Glucose Fats Proteins Glycolysis TCA Cycle ETC b-oxidation TCA Cycle ETC Deamination TCA Cycle ETC

23. Chemical Energy Cars Gasoline Cells ATP

24. When this process is dysfunctional , then disease can occur.

25. Mitochondrial cytopathies are diseases of energy production .

26. Epidemiology Are these diseases common?

30. Mitochondrial Inheritance

35. Mitochondrial Inheritance Multiple organ disease

39. Maternal genetic transmission An affected woman transmits the trait to all her children . Affected men (represented by squares do not pass the trait to any of their offspring

40. Clinical Manifestation of Mitochondrial Dysfunction Multiple organ disease

48. mtDNA-related Syndromes 1.M itochondrial e ncephalopathy, l actic a cidosis and s troke-like episodes ( MELAS ) 2 .Aminoglycoside-induced deafness 3 .Cyclic vomiting syndrome

49. mtDNA-related Syndromes (cont.) 4 .Kearns-Sayre syndrome ( KSS ) 5 .Pearson syndrome 6 .Leigh disease 7.N europathy , a taxia and r etinitis p igmentosa (NARP)

50. mtDNA-related Syndromes (cont.) 8.M itochondrial n euro g astro i ntestinal e ncephalopathy ( MNGIE) 8.M yoclonic e pilepsy and r agged- r ed f iber disease ( MERRF ) 9.L eber’s h ereditary o ptic n europathy ( LHON )

51. Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like Episodes (MELAS)

53. Mitochondrial encephalopathy, lactic acidosis and cerebrovascular accident syndrome ( MELAS ) Mitochondrial encephalopathy, lactic acidosis and cerebrovascular accident syndrome (MELAS) in PICU

54. Mitochondrial encephalopathy, lactic acidosis and cerebrovascular accident syndrome ( MELAS ) Mitochondrial encephalopathy, lactic acidosis and cerebrovascular accident syndrome (MELAS) in PICU

58. MELAS : Mitochondrial staining of intramuscular vessels Succinic dehydrogenase (SDH) stain Increased SDH staining of a medium sized perimysial vessel in a MELAS patient. Normal : Mild SDH staining of a medium sized perimysial vessel.

60. MRI during episode of hemiparesis FLAIR image T2 weighted image T2 weighted image FLAIR image

61. CT during episode of homonymous hemianopia Medial occipital lesion (Arrow) Enlarged ventricles

62. MELAS : Muscle fiber pathology Scattered abnormal, vacuolated fibers with clear rim : H & E Scattered "ragged red" muscle fibers : Gomori trichrome

63. Late in disease course MRI: Severe involvement of occipital cortex Severly abnormal temporal gray matter. Temporal horn of ventricles is enlarged.

64. Diagnosis of Mitochondrial Cytopathies 1.Clinical Exam and History 2.Lab Results 3.CNS Imaging 4.Biopsy Data

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