NP3D

Question 1

in this condition, the cerebellum forms normally, but then we begin to see progressive signs of cerebellar dysfunction between birth and nine months of age. (shown to follow an autosomal recessive mode of inheritance)

Answer 1

Cerebellar abiotrophy

Question 2

degeneration or loss of function or vitality in an organism or in cells or tissues not due to any apparent injury

Answer 2

abiotrophy

Question 3

Cerebellar abiotrophy: in the dog, the genetic change disrupts function of a protein known as __________

Answer 3

Parkin, directs abnormal proteins in the cell to the proteasome for degradation

Question 4

Cerebellar abiotrophy: The expression of this defect is surprising in that the _____________ is the primary organ affected

Answer 4

cerebellum

Question 5

Cerebellar abiotrophy: ___________ is the basis for a definitive diagnosis, showing selective necrosis of Purkinje cells, with secondary thinning of the molecular cell layer and loss of cellularity in the internal granular cell layer

Answer 5

Histology

Question 6

The changes do not cause a notable reduction in size of the cerebellum except in more severe forms, and then it generally requires a more quantitative analysis of MRI data

Answer 6

Cerebellar abiotrophy

Question 7

clinical signs are progressive from birth

Answer 7

cerebellar abiotrophy

Question 8

clinical signs do not progress

Answer 8

cerebellar hypoplasia

Question 9

Histologically: we see necrotic Purkinje cells and no evidence of dysplasia

Answer 9

abiotrophy

Question 10

Histologically: cells are simply missing and the tissue is disorganized (dysplastic)

Answer 10

hypoplasia

Question 11

Lysosomal storage disorders:
A defect in the _________ will result in a more dramatic accumulation of the enzyme’s substrate and this is associated with a more rapid progression of clinical neurological disease

Answer 11

active site

Question 12

Lysosomal storage disorders:
Defects in the _________ will have lesser effects on overall enzyme function and will be associated with a slower progression of disease.

Answer 12

regulatory site

Question 13

Lysosomal storage disorders: Defects follow an autosomal recessive mode of inheritance. Clinical disease is expressed in _______

Answer 13

homozygotes

Question 14

What is it about lysosomal storage that creates problems?

Answer 14

• Accumulated material may be directly toxic to the cell, or metabolites from alternate catabolic pathways may be toxic to the cell.
• Accumulated material may be a physical impediment to neuronal axoplasmic transport.

Question 15

Diagnosing a lysosomal storage disorder:

Answer 15

• diagnosis can be made antemortem
• treated with gene replacement therapy, bone narrow transplant
• classified according to the material that accumulates as a consequence of the enzyme deficiency: lipidosis, glycoproteinosis, and mucopolysaccharidosis. There are multiple specific enzyme defects that can give rise to a lipidosis, glycoproteinosis or mucopolysaccharidosis.

Question 16

disease in a cat, which is a sphingolipidosis

Answer 16

Niemann-Pick

Question 17

a unique type of neuron-specific to the cerebellar cortex

Answer 17

Purkinje cell

Question 18

Storage disorders can also be acquired:

Answer 18

Unfortunately, nobody agrees on the dose of chloroquine for penguins and the levels used here were excessive. Fortunately, lesions are reversible and the chloroquine dose was adjusted for the surviving penguins and they subsequently recovered

Question 19

Acquired _____________ are observed in herbivores following ingestion of certain plants

Answer 19

glycoproteinoses

Question 20

lysosomal storage diseases affecting glycoproteins, resulting from defects in lysosomal function

Answer 20

glycoproteinoses

Question 21

There is one storage disorder that is classified as a ____________

Answer 21

proteinosis

Question 22

the accumulation of abnormal amounts of protein in bodily tissues (in the cytoplasm)

Answer 22

proteinosis

Question 23

This is not a lysosomal storage disease, but rather a defect in protein and lipid trafficking within the cell (in some ways similar to what we discussed in cerebellar abiotrophy). But instead of dying, the cells accumulate aggregates of protein and lipid that are highlighted with a special stains (acid-fast, in which granules attain a purplish-red), giving rise to a more protracted loss of function. Microscopic examination of tissues using a UV light source also shows the inclusions to autofluorescence yellow – the definitive diagnosis is easy to make.

Answer 23

ceroid lipofuscinosis

Question 24

Niemann-Pick also affects Schwann cells in the ___________, resulting in a polyneuropathy. Illustrated is loss of myelin, collapse of the Schwann cell-associated endoneurium, and accumulation of lipid-laden phagocytes

Answer 24

periphery