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Flashcards in Mitochondrial Disease Deck (29):
0

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

CNS
Muscles
Cardiac
GI system including Liver
Kidneys

1

what are some brain associated symptoms of Mito diseases?

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

2

what are some effects on Nerves in mito diseases?

absent reflexes
fainting
neuropathic pain
weakness
dysautonomia - temperature instability

3

what are some associated Pancreas issues?

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

4

what is different about strokes in pts with Mito disorders?

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

5

what are some muscle issues?

weakness
cramping
hypotonia
muscle pain

6

what are some common problems in Mitochondrial energy disorders?

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

7

mitochondrial genes are inherited exclusively from

mom

8

what are some methods to test for mitochondrial disease?

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

9

What findings would strongly suggest mitochondrial energy disorders?

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

10

what are some GI issues?

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

11

Kidney issues?

renal tubular acidosis or wasting

12

Heart issues?

cardiomyopathy
cardiac conduction defects - heart blocks

13

Liver issues?

liver failure
hypoglycemia - low blood sugar

14

Ear or eye issues?

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

15

what are some systemic issues?

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

16

Heteroplasmy of mtDNA

explains varying degrees of mito disorders

17

what is a typical test to diagnosis Mito energy disorders?

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

18

How often are ragged red fibers seen?

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

19

what does testing of skin fibroblasts and buccal swabs allow?

less invasive biopsy
OXPHOS assays

20

mtDNA screening screens

37 maternally inherited genes
there are about 1500 genes involved in mitochondrial energy production

21

what are some metabolic abnormalities that support mitochondrial disease?

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

22

treatments are limited but include

CoQ10
L-carnitine
Riboflavin
Alpha lipoic acid
Creatine

23

what is Autism ?

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

24

Do vaccines cause Autism?

NO!!!!

25

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

reduced mitochondrial enzyme function
Complex 1 was affected

26

Before screening for Mitochondrial disorder, check for ...

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

27

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

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

28

What are some tier 2 tests for ASD patients?

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