Metabolic Diseases Flashcards
What are two types of Metabolic Diseases?
- Genetic Metabolic Disease
2. Toxic and acquired metabolic diseases
What are some genetic metabolic diseases?
- Neuronal storage diseases
- Leukodystrophies
- Usually show up in childhood, also called inborn errors of metabolism
- Missing an enzyme or have low levels of it when you’re born
What are some toxic and acquired metabolic diseases?
- Vitamin deficiencies
- Metabolic and toxic disturbances
- Things you might be exposed to , or something that you’re not getting enough of
What are neuronal storage diseases?
-Autosomal recessive enzyme deficiency
-Result: accumulation of enzyme substrate (sphinolipids, mucopolysaccharides or mucolipids) with neuronal lysosomes
-Leads to loss of cognitive function, maybe also seizures
Ex: neuronal ceroid lipofuscinoses, Tay-Sachs disease
-oses ?
means accumulation
What is Neuronal Ceroid Lipofuscinoses?
- 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
What is Tay-Sachs Disease? KNOW
- Deficiency in Hexosaminidase A
- Accumulation of ganglioside in all tissues (but nervous system shows the most symptoms)
- Ganglioside accumulation kills the cells
- Autosomal recessive, more common in Ashkenazi Jews
- Usually begins in early infancy (ex: eyes aren’t tracking like they should, progresses to motor deficits)
- Developmental delay, then paralysis and loss of neurologic function
- Death within several years
What is ganglioside?
It is ‘food’ for a neuron.
What neurons are typical of storage diseases?
Ballooned neurons! (LARGE)
What do neurons look like in Tay-Sachs?
Show accumulation of ganglioside! Very large vacuoles filled with white material
What is the diagnostic clue for Tay-Sachs?
KNOW
“Cherry-red” spot in retina
- Macula looks very red
- As neurons get stuffed with ganglioside they turn whiteish/opaque - macula really stands out!
What are leukodystrophies?
- Group of disorders characterized by myelin abnormalities
- Most are autosomal recessive
- Involved lysosomal or peroxisomal enzymes (DON’T NEED TO KNOW)
- Deterioration of motor skills, spasticity, hypotonia, ataxia (Main difference btw neuronal and storage disorders)
What is Krabbe Disease?
(DON’T NEED TO KNOW)
- Deficiency of galactosylceramidase
- Galactocerebroside accumulates, gets converted to galactrosylsphingosine (toxic to oligodendrocytes)
- Macrophages become very large from eating dead oligodendrocytes
- Loss of myelin and oligodendrocytes in CNS and peripheral nerves
- “Globoid cells” (fat macrophages) in the brain
- Onset around 3-6 months
What is B1 (Thiamine Deficiency)?
- Usually associated with chronic alcoholism
- Mammillary bodies affected most
- Wernicke encephalopathy [1st stage]
- –Confusion, ophthalmoplegia, ataxia (gait disturbance)
- –Hemorrhage and necrosis in mammillary bodies, walls of third and fourth ventricles
- –Acute, reversible (at least the eye findings and ataxia, maybe not confusion)
- Korsakoff syndrom [2nd stage - not reversible!]
- –Memory disturbances, confabulation (story patient believes because they can’t fill a blank space in time where they blacked out - so their brain makes up a story)
- –Cystic spaces, hemosiderin-laden macrophages in mammillary bodies, ventricle walls
- Thalamic lesions too
- Prolonged, mostly irreversible
Why do we need thiamine?
To make ATP, keep astrocytes working properly
