Metabolic Diseases (finished)

Question 1

Define neuronal storage diseases

Answer 1

Build up in neurons
Autosomal recessive enzyme deficiency
Result: accumulation of enzyme substrate (sphingolipids, mucopolysaccharides or mucolipids) within neuronal lysosomes
Leads to a loss of cognitive function, maybe also seizures.
Neuronal ceroid lipofuscinoses, Tay-Sachs disease

Deficiency of enzymes involved in protein modification/degradation
Lipofuscin (accumulates normally in rest of body with age, but NOT normal in neurons) accumulates within neurons, leading to neuronal dysfunction
Blindness, mental and motor deterioration, seizures
Onset ranges from childhood to adulthood

Good indicator: normal at birth, but then starts missing developmental milestones

Motor symptoms less major, cognitive symptoms more major, when compared to leuko

Question 2

leukodystrophies

Answer 2

build up in white matter, myelin

Group of disorders characterized by myelin abnormalities
Most are autosomal recessive
Involve lysosomal or peroxisomal enzymes
Deterioration of motor skills, spasticity, hypotonia, ataxia

Good indicator: normal at birth, but then starts missing developmental milestones

Motor symptoms more major, cognitive symptoms less major, when compared to NSD

Question 3

Identify the substance that is abnormally accumulated in neuronal ceroid lipofuscinoses

Answer 3

Deficiency of enzymes involved in protein modification/degradation
Lipofuscin accumulates within neurons, leading to neuronal dysfunction
Blindness, mental and motor deterioration, seizures
Onset ranges from childhood to adulthood
How does the enzyme deficiency lead to accumulation of lipofuscin?!

Question 4

Compare and contrast the inheritance pattern, enzyme deficiency, clinical features, and histologic findings in Krabbe disease.

Answer 4

Deficiency of galactosylceramidase
Galactocerebroside accumulates, gets converted to galactosylsphingosine (toxic to oligodendrocytes)
Loss of myelin and oligodendrocytes in CNS and peripheral nerves
“Globoid cells” (fat macrophages) in brain
Onset around 3-6 months
Rapidly progressive muscle stiffness, weakness

Question 5

Describe the clinical features and histologic findings seen in the CNS in:
thiamine deficiency

Answer 5

aka vitamin B1 deficiency
Usually associated with chronic alcoholism
Wernicke encephalopathy
-confusion, ophthalmoplegia, ataxia
-hemorrhage and necrosis in mammillary bodies, walls of third and fourth ventricles
-acute, reversible
Korsakoff syndrome
-memory disturbances, confabulation (making up and believing stories)
-cystic spaces, hemosiderin-laden macrophages in mammillary bodies, ventricle walls
-thalamic lesions too
-prolonged, mostly irreversible

Question 6

Describe the clinical features and histologic findings seen in the CNS in:
B12 deficiency

Answer 6

Anemia
-reversible with B12 administration
Subacute combined degeneration of spinal cord
-lower extremity numbness, ataxia, weakness
-reversible until paraplegia occurs
-swelling of myelin layers, vacuolization
-ascending and descending tracts involved

Question 7

Describe the clinical features and histologic findings seen in the CNS in:
hypoglycemia

Answer 7

Most vulnerable: large pyramidal neurons of cortex (“pseudolaminar necrosis”)
Also vulnerable: hippocampus and cerebellum

Question 8

Describe the clinical features and histologic findings seen in the CNS in:
hyperglycemia

Answer 8

Most commonly seen in diabetes mellitus
Can be associated with either ketoacidosis or hyperosmolar coma
Dehydration, confusion, stupor, coma

Question 9

Describe the clinical features and histologic findings seen in the CNS in:
carbon monoxide poisoning

Answer 9

Injury is due to hypoxia
Particularly vulnerable areas: 
cortex (layers III and V)
hippocampus
Purkinje cells
May see demyelination of white matter tracts

Question 10

Describe the clinical features and histologic findings seen in the CNS in:
methanol toxicity

Answer 10

Preferentially affects retina
Degeneration of ganglion cells
May cause blindness

Question 11

Describe the clinical features and histologic findings seen in the CNS in:
ethanol toxicity.

Answer 11

Acute effects are reversible; chronic effects are not
Preferentially affects cerebellum
Truncal ataxia, unsteady gait, nystagmus
Cerebellar atrophy, loss of granule cells, loss of Purkinje cells, Bergmann gliosis (a line of gliosis)

Question 12

metabolic diseases are often the result of missing an enzyme, lead to buildup

Answer 12

know this

Question 13

Identify the substance that is abnormally accumulated in Tay-Sachs disease.

Answer 13

Deficiency of hexosaminidase A
Accumulation of ganglioside in all tissues (nervous system shows the most symptoms)
Autosomal recessive; much more common in Ashkenazi Jews (Central European)
Usually begins in early infancy
Developmental delay, then paralysis and loss of neurologic function
Death within several years

“Cherry-red” spot in retina virtually diagnostic