Mitochondrial Disease

Question 0

what are some brain associated symptoms of Mito diseases?

Answer 0

developmental delays 
migraines 
seizures 
dementia 
autistic features 
atypical cerebral palsy 
neuro-psychiatric disturbances 
strokes

Question 1

what are some of the main organ systems affected by Mitochondrial disease?

Answer 1

CNS 
Muscles 
Cardiac 
GI system including Liver 
Kidneys

Question 2

what are some effects on Nerves in mito diseases?

Answer 2

absent reflexes 
fainting 
neuropathic pain 
weakness 
dysautonomia - temperature instability

Question 3

what are some associated Pancreas issues?

Answer 3

diabetes and exocrine pancreatic failure - inability to make digestive enzymes
parathyroid failure - low calcium

Question 4

what is different about strokes in pts with Mito disorders?

Answer 4

mitochondria in the smooth muscles cells of the vessels in the brain cause spasms or uncoordinated activities that may lead strokes

difference is that strokes are not due to thrombotic events

Question 5

what are some muscle issues?

Answer 5

weakness
cramping
hypotonia
muscle pain

Question 6

what are some common problems in Mitochondrial energy disorders?

Answer 6

central nervous system problems - developmental delays including Austism and Autistic features, loss of function, seizures, hypotonia & weakness
failure to thrive
chronic fatigue
gastrointestinal issues such as chronic constipation
autonomic dysfunction such as irregular heart rate and blood pressure and temperature instability with heat intolerance

Question 7

mitochondrial genes are inherited exclusively from

Answer 7

mom

Question 8

what are some methods to test for mitochondrial disease?

Answer 8

functional testing - examining the OXPHOS energy pathway
gene testing - evaluate mtDNA and nuclear mitochondrial genes
biomarker studies - lactate and pyruvate levels, CSF lactate, CPK, urine organic acids, carnitine levels
Radiographic studies - identification of mito related imaging abnormalities

Question 9

What findings would strongly suggest mitochondrial energy disorders?

Answer 9

brain changes suggestive of Leigh disease or abnormalities in white matter
persistent, significant elevation in lactate (esp. if in the brain) and other specific biochemical features
problems in many body systems
strong family history

Question 10

what are some GI issues?

Answer 10

pseudo-obstruction 
dysmotility 
irritable bowel syndrome 
gastroesophogeal reflux 
diarrhea or constipation

Question 11

Kidney issues?

Answer 11

renal tubular acidosis or wasting

Question 12

Heart issues?

Answer 12

cardiomyopathy

cardiac conduction defects - heart blocks

Question 13

Liver issues?

Answer 13

liver failure

hypoglycemia - low blood sugar

Question 14

Ear or eye issues?

Answer 14

visual loss and blindness 
ptosis 
ophthalmoplegia 
optic atrophy 
hearing loss and deafness 
acquired strabismus 
retintis pigmentosa

Question 15

what are some systemic issues?

Answer 15

failure to gain weight 
chronic fatigue 
unexplained vomiting 
short stature 
respiratory problems

Question 16

Heteroplasmy of mtDNA

Answer 16

explains varying degrees of mito disorders

Question 17

what is a typical test to diagnosis Mito energy disorders?

Answer 17

muscle tissue biopsy - allows to assess mito structure/size/shape/number
test enzymatic abnormalities of energy producing systems
respirometry studies to measure oxygen comsumption
blue and clear native gels studies to assess protein complexes and supercomplexes to ID defects

Question 18

How often are ragged red fibers seen?

Answer 18

less than 2.5% of cases
in peds pt, usually normal
most often seen in adult pts with mtDNA gene defects

Question 19

what does testing of skin fibroblasts and buccal swabs allow?

Answer 19

less invasive biopsy

OXPHOS assays

Question 20

mtDNA screening screens

Answer 20

37 maternally inherited genes

there are about 1500 genes involved in mitochondrial energy production

Question 21

what are some metabolic abnormalities that support mitochondrial disease?

Answer 21

increased blood and/or CSF lactate and pyruvate and/or ratio
decreased plasma carnitine
increased blood alanine
generalized aminoaciduria
increase lactate, pyruvate, kreb cycle intermediates, tiglyglycine and 2-oxoadipic acid

Question 22

treatments are limited but include

Answer 22

CoQ10
L-carnitine 
Riboflavin 
Alpha lipoic acid 
Creatine

Question 23

what is Autism ?

Answer 23

complex neurobiological disorder
part of group of disorders ASD
associated with rigid routines and repetitive behaviors
cause largely unknown

Question 24

Do vaccines cause Autism?

Answer 24

NO!!!!

Question 25

In a UC Davis study, it was found that 60% of ASD pts had …

Answer 25

reduced mitochondrial enzyme function

Complex 1 was affected

Question 26

Before screening for Mitochondrial disorder, check for …

Answer 26

chromosome abnormalities
inborn errors of metabolism
any other disorders related to the clinical presentations

Question 27

What are some suggested Tier 1 work ups for ASD patients?

Answer 27

chromosome microarray 
complete metabolic panel, CBC, CPK
ammonia level 
lactate and pyruvate levels 
carnitine
CoQ10 
plasma and urine AA
urine organic acids 
plasma acylcarnitines 
thyroid function tests

Question 28

What are some tier 2 tests for ASD patients?

Answer 28

mitochondrial enzyme and/or DNA testing 
Rett syndrome DNA testing 
PTEN mutational analysis 
Gene testing 
lysosomal enzyme testing 
peroxisome disease testing 
CSF studies for lactate and pyruvate, AA and neurotransmitters 
brain MRI