Genetic Metabolic Diseases

Question 1

Leukodystrophies involve abnormalities in?

Answer 1

Myelin abnormalities – white matter involvement of the brain

Question 2

Leukodystrophies involve abnormalities in?

Answer 2

Myelin abnormalities – white matter involvement

Question 3

What enzyme is deficient with Krabbe Disease (leukodystrophy)?

Answer 3

Galactocerebroside B-Galactosidase

Question 4

Krabbe disease (leukodystrophy) uses an alternate pathway that generates a toxic metabolite to the oligodendroglia. What is that metabolite?

Answer 4

Galactosylsphingosine

Question 5

With Krabbe Disease (leukodystrophy) there will be motor signs when the child is 3-6 months old. What cells are present?

Answer 5

Globoid cells = engorged macrophages aggregating

Question 6

Globoid cells are engorged macrophages. What leukodystrophy are they seen with?

Answer 6

Krabbe Disease

Question 7

What enzyme is deficient with Metachromatic Leukodystrophy?

Answer 7

Arylsulfatase A

Question 8

What metabolite accumulates with Metachromatic Leukodystrophy?

Answer 8

Cerebroside Sulfates

Question 9

With Metachromatic Leukodystrophy, Cerebroside Sulfate accumulates and can bind to a toluidine blue stain. What will that show in the brain?

Answer 9

Metachromasia (colorful)

Question 10

How is Adrenoleukodystrophy inherited?

Answer 10

X-linked

Question 11

What gene is mutated with Adrenoleukodystrophy?

Answer 11

ABCDE1

Question 12

What accumulates with Adrenoleukodystrophy?

Answer 12

VLCFAs

Question 13

What is the unique symptom with Adrenoleukodystrophy?

Answer 13

Adrenal insufficiency and myelin loss

Question 14

How is Pelizoeus-Merzbacher Disease (leukodystrophy) inherited?

Answer 14

X-linked

Question 15

What symptom is present with Pelizoeus-Merzbacher DIsease?

Answer 15

Pendular eye movements

Question 16

With Pelizoeus-Merzbacher Disease, the myelin is completely lost. The patches that remain are seen as?

Answer 16

Tigroid pattern

Question 17

With Canavan Disease (leukodystrophy), what enzyme is deficient?

Answer 17

Aspartoacylase

Question 18

With Canavan Disease (leukodystrophy), what accumulates?

Answer 18

Acetylaspartic Acid

Question 19

What histo change in the white matter occurs with Canavan Disease (Leukodystrophy)?

Answer 19

Spongiform degeneration of the white matter

Question 20

What symptoms are present with Canavan Disease (leukodystrophy)?

Answer 20

Megacephaly

Blindness

Question 21

What mutation is present with Alexander Disease (leukodystrophy)?

Answer 21

GFAP mutation

Question 22

What accumulates around blood vessels with Alexander Disease (leukodystrophy)?

Answer 22

Rosenthal fibers around vessels

Question 23

What do Mitochondrial Encephalomyopathies involve?

Answer 23

Gray matter and SKELETAL MUSCLE

Question 24

Mitochondrial Encephalomyopathies are inherited from which parent?

Answer 24

Mother

Question 25

What are the 2 Mitochondrial Encephalomyopathies?

Answer 25

MELAS | MERRF

Question 26

MELAS mutation

Answer 26

MTTL1

Question 27

What are the signs of MELAS?

Answer 27

Muscle weakness with lactic acidosis | Stroke-like episodes

Question 28

Muscle weakness with lactic acidosis and stroke-like episodes could be which Mitochondrial Encephalomyopathy?

Answer 28

MELAS

Question 29

What is weird about the stroke-like episodes with MELAS?

Answer 29

Deficits do not correspond to vascular territories

Question 30

What mutation is present with MERRF?

Answer 30

tRNA mutations

Question 31

What histo item is seen with MERRF?

Answer 31

Ragged red fibers

Question 32

What are the 2 symptoms of MERRF?

Answer 32

Myoclonus and seizures

Question 33

Thiamine Deficiency (B1) is usually seen in what type of patients?

Answer 33

Chronic Alcoholics

Question 34

What is the reversible Thiamine (B1) deficiency?

Answer 34

Wernicke Encephalopathy

Question 35

What will be seen on the brain with Wernicke Encephalopathy (thiamine/B1 deficient)?

Answer 35

Hemorrhage and necrosis of mamiillary bodies

Question 36

Hemorrhage and necrosis of mamillary bodies is seen with?

Answer 36

Wernicke Encephalopathy | -- thiamine (B1) deficiency

Question 37

What is the irreversible Thiamine (B1) deficiency?

Answer 37

Korsakoff Syndrome

Question 38

Symptoms of Korsakoff syndrome?

Answer 38

Memory issues and confabulation

Question 39

With B12 deficiency, what degenerates?

Answer 39

Ascending and Descending axons = subacute combined degeneration

Question 40

Subacute combined degeneration (loss of ascending and descending axons) is seen with what vitamin deficiency?

Answer 40

B12 deficiency

Question 41

What histo change is seen with Hypoglycemia in the brain?

Answer 41

Pseudolaminar necrosis

Question 42

Pseudolaminar necrosis

Answer 42

Hypoglycemia

Question 43

Hyperglycemia does not involve brain changes. What are the symptoms?

Answer 43

Confusion, stupor, coma

Question 44

What 2 things can be associated with Hyperglycemia?

Answer 44

Ketoacidosis | Hyperosmolar coma

Question 45

Hepatic Encephalopathy is impaired liver function that causes what metabolite to accumulate in the brain?

Answer 45

Ammonia

Question 46

What cells will be seen with Hepatic Encephalopathy?

Answer 46

Alzheimer Type 2 cells

Question 47

Carbon Monoxide changes to the brain?

Answer 47

Bilateral necrosis of globus pallidi

Question 48

Bilateral necrosis of globus pallidi suggest?

Answer 48

Carbon monoxide poisoning

Question 49

Methanol causes what cells to degenerate and why?

Answer 49

Retinal ganglion cells due to formate

Question 50

What brain change is seen with Methanol consumption?

Answer 50

Bilateral putamenal necrosis

Question 51

Bilateral putamenal necrosis suggests?

Answer 51

Methanol poisoning

Question 52

What part of the brain atrophies with Ethanol?

Answer 52

Anterior vermis of cerebellum

Question 53

Histo change with Ethanol consumption?

Answer 53

Bergmann gliosis

Question 54

What is Bergmann Gliosis?

Answer 54

Decreased purkinje cells and astrocyte proliferation

Question 55

What part of the brain atrophies with Ethanol consumption?

Answer 55

Anterior vermis of cerebellum