Path - Demyelinating Flashcards
What is a leukodystrophy disease?
Inherited disturbances in the formation and preservation of myelin
What are three leukodystrophies?
What are the inheritance patterns?
Metachromatic leukodystrophy, Krabbe disease (Globoid cell Leukodystrophy, GCLD), and Adrenoleukodystrophy (ALD)
MLD and GCLD are autosomal recessive. ALD is x-linked recessive
What accumulates in metachromatic leukodystrophy?
Cerebroside sufates sulfatides (lipids that contain sulfate
Describe Pathology of Metachromatic Leukodystrophy
Accumulation of sulphatides (from a defective arylsufatase-A) cause demyelination and gliosis.
Macrophages containing sulfatides
How is Metachromatic Leukodystrophy diagnosed?
Macrophages containing sulfatides bind dyes and become metachromasia. Detecting metachromatic in urine is good diagnostic
What is Krabbe disease?
A deficiency in Galactocerbroside B-galatosidase enzyme. The alternative pathway for the breakdown of galactocerebroside creates toxic galactosylsphigosine. The accumulation causes oligodendrocyte and schwann cell injury
Krabbe disease is also called what?
Globoid Cell Leukodystrophy
What accumulates in Krabbe? Where?
Also called Globoid cell leukodystrophy because of the accumulation of Globoid cells which are multinucleated macrophages. Around the blood vessels
Describe ALD.
Adrenoleukodystrophy
X-linked disorder of the Adrenal cortex
with demyelination of the nervous system
Increase in levels of very long chain FA in children and body fluids because of enzyme mutation that degrades VLCFA’s
Increases blood pressure
Also occurs in children 4-8 yrs old
Who get leukodystrophies?
Children
MLD = infants; lethal within several years
GCLD = ~ 2 years leathal
ALD = 4-8 yrs
Where does Adrenoleukodystrophy degeneration occur?
Cortical white matter of the parietal and occipital regions
What laboratory signs will be in ADL?
Serum levels of increase VLCFA’s
Atrophied adrenal glands will also have high levels of VLCFA’s
Describe Alexander disease.
Also called Rosenthal Fiber Encephalopathy or fibrinoid leukodystrophy.
Occurs in a mutation of the GFAP (Glial Fibrillay Acidic protein) that causes the formation of Rosenthal fibers.
The extracellular accumulation of Rosenthal fibers cause the degeneration of myelin in the brain`
Who gets Alexander disease? Prognosis?
Children and infants mostly get Rosenthal fiber encephalopathy that cause phsychomotor retardation, progressive dementia, paralysis and death
What is Multiple Sclerosis
An autoimmune demyelinating disease that attacks the CNS but spares the PNS
Who gets Multiple sclerosis?
Young adults in 30-40s
People in colder climates