Toxic & Metabolic CNS diseases

Question 1

How are most autosomal LSDs inherited?

Answer 1

autosomal recessive

Question 2

Which LSDs are X linked?

Answer 2

fabry disease
hunter syndrome (MPS II)

Question 3

What is the definition of a gangliosidoses?

Answer 3

type of neuronal storage disease

Question 4

What is a lysosomal storage disease?

Answer 4

accumulation of ‘inert’ substrates/metabolites

cells swell

Question 5

What population is tay sachs usually seen in?

Answer 5

ashkenazi jews

Question 6

What chromosome is the gene for tay sachs on?

Answer 6

15

Question 7

What are the signs and symptoms of tay sachs?

Answer 7

psychomotor retardation
blindness
motor incoordination, eventual flaccidity, mental deterioration, eventual decerebrate state
cherry red spot

Question 8

What is stored excessively in tay sachs?

Answer 8

Hex A: aB

Question 9

What is stored excessively in sandhoff disease?

Answer 9

Hex B: BB

Question 10

What happens to a tay sachs brain if the patient survives longer than 2 years?

Answer 10

gets big

Question 11

What microscopic findings are in tay sachs disease?

Answer 11

enlarged ballooned neurons filled with PAS positive material/whorled, membranous cytoplasmic bodies

Question 12

What is deficient in Krabbe’s disease? What does this result in?

Answer 12

galactocerebroside B galactosidase

accum of toxic compound (psychosine) that injures oligodendrocytes

Question 13

What is another name for Krabbe’s disease?

Answer 13

globoid cell leukodystrophy

Question 14

What are clinical signs and symptoms of Krabbe’s?

Answer 14

irritability
tonic spasms
opisthotonic posture
myotonic jerking
optic atrophy, blindness

Question 15

What does Krabbe’s look like on gross exam?

Answer 15

atrophic white matter with preservation of U fibers

Question 16

What is seen histologically with krabbe’s?

Answer 16

globoid cells
large multinucleated cells
globoid cells contain crystalloid straight or tubular profiles

Question 17

What is deficient in metachromatic leukodystrophy? What does this result in?

Answer 17

aryl sulfatase A
metachromic lipids (sulfatides) accumulate in brain, peripheral nerves and kidney

Question 18

How is metachromatic leukodystrophy diagnosed?

Answer 18

enzme deficiency in urine, WBCs or fibroblasts

Question 19

What does metachromatic leukodystrophy look like on gross exam?

Answer 19

white matter very firm, gliosis, preservation of U fibers

Question 20

What is seen on histology for metachromatic leukodystrophy?

Answer 20

metachromasia of white matter deposits (acidified cresyl violet stain)

Question 21

What is the problem in adrenoleukodystrohpy?

Answer 21

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)

Question 22

What are the signs/symptoms of the adrenoleukodystrophy classic form?

Answer 22

dementia/psychosis, visual/hearing loss, seizures, adrenall insufficiency follows neuro sx

Question 23

What does adrenoleukodystrophy look like on gross exam?

Answer 23

gray discoloration of white matter, marked firmness
u fiber preservation
severe demyelination

Question 24

What does adrenoleukodystrophy look like histologically?

Answer 24

perivascular inflammation (more specific)
PAS positive macrophages

Question 25

What is the important histologic finding related to hepatic encephalopathy?

Answer 25

alzheimer type II astrocytes

Question 26

What systems are most commonly symptomatic in mitochonidrail disease?

Answer 26

brain & muscle

Question 27

What is the mutation in leigh's disease (subacute necrotizing encephalopathy)?

Answer 27

mutation in nuclear DNA and mitochondrial DNA leading t oenzyme deficiency in pathyway converting pyruvate to ATP decreased activity of cytochrome C oxidase

Question 28

What are the signs and symptoms of leigh's disease?

Answer 28

arrest of development, hypotonia, seizures, extraocular palsies

Question 29

What is seen on gross exam of leigh's patients?

Answer 29

multifocal infarcts that don't correspond to vascular distribution

Question 30

What are signs/sx of fetal alcohol syndrome?

Answer 30

``` growth retardation facial deformities (short palpebral fissue, epicanthal folds, thin upper lip, growth retardation of jaw) cardiac defects delayed develpment and mental deficiency ```

Question 31

What is seen histologically with methotrexate toxicity?

Answer 31

coagulative necrosis with mineralization

Question 32

What would lead you to a dx of sandhoff's over tay sachs?

Answer 32

more severe presentation | PNS and CNS findings