Toxic & Metabolic CNS diseases Flashcards
How are most autosomal LSDs inherited?
autosomal recessive
Which LSDs are X linked?
fabry disease hunter syndrome (MPS II)
What is the definition of a gangliosidoses?
type of neuronal storage disease
What is a lysosomal storage disease?
accumulation of ‘inert’ substrates/metabolites
cells swell
What population is tay sachs usually seen in?
ashkenazi jews
What chromosome is the gene for tay sachs on?
15
What are the signs and symptoms of tay sachs?
psychomotor retardation
blindness
motor incoordination, eventual flaccidity, mental deterioration, eventual decerebrate state
cherry red spot
What is stored excessively in tay sachs?
Hex A: aB
What is stored excessively in sandhoff disease?
Hex B: BB
What happens to a tay sachs brain if the patient survives longer than 2 years?
gets big
What microscopic findings are in tay sachs disease?
enlarged ballooned neurons filled with PAS positive material/whorled, membranous cytoplasmic bodies
What is deficient in Krabbe’s disease? What does this result in?
galactocerebroside B galactosidase
accum of toxic compound (psychosine) that injures oligodendrocytes
What is another name for Krabbe’s disease?
globoid cell leukodystrophy
What are clinical signs and symptoms of Krabbe’s?
irritability tonic spasms opisthotonic posture myotonic jerking optic atrophy, blindness
What does Krabbe’s look like on gross exam?
atrophic white matter with preservation of U fibers
What is seen histologically with krabbe’s?
globoid cells
large multinucleated cells
globoid cells contain crystalloid straight or tubular profiles
What is deficient in metachromatic leukodystrophy? What does this result in?
aryl sulfatase A metachromic lipids (sulfatides) accumulate in brain, peripheral nerves and kidney
How is metachromatic leukodystrophy diagnosed?
enzme deficiency in urine, WBCs or fibroblasts
What does metachromatic leukodystrophy look like on gross exam?
white matter very firm, gliosis, preservation of U fibers
What is seen on histology for metachromatic leukodystrophy?
metachromasia of white matter deposits (acidified cresyl violet stain)
What is the problem in adrenoleukodystrohpy?
decreased activity of very long chain fatty acyl CoA synthetase
(excess of very long chain fatty acid esters in plasma, cultured fibroblasts, CNS, PNS and adrenals)
What are the signs/symptoms of the adrenoleukodystrophy classic form?
dementia/psychosis, visual/hearing loss, seizures, adrenall insufficiency follows neuro sx
What does adrenoleukodystrophy look like on gross exam?
gray discoloration of white matter, marked firmness
u fiber preservation
severe demyelination
What does adrenoleukodystrophy look like histologically?
perivascular inflammation (more specific) PAS positive macrophages
