Metabolic Diseases

Question 1

Tay-Sachs Disease

Answer 1

• Deficiency of hexosaminidase A
• Accumulation of ganglioside (GM2) in all tissues (nervous system shows the most symptoms) – causes bulging tumors
• Ganglioside GM2 is found in membranes
• Autosomal recessive; much more common in Ashkenazi Jews
• 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
• Occurs on the fovea – area surrounding is effected

Question 2

Neuronal Ceroid Lipofuscinoses

Answer 2

1. Deficiency of enzymes involved in protein modification/degradation
2. Lipofuscin accumulates within neurons, leading to neuronal dysfunction
3. Lipofuscin is a normal pigment that accumulates with aging
4. Blindness, mental and motor deterioration, seizures
5. Onset ranges from childhood to adulthood

Question 3

Leukodystrophies - Krabbe disease

Answer 3

1. Deficiency of galactosylceramidase
2. Galactocerebroside accumulates, gets converted to galactosylsphingosine (toxic to oligodendrocytes)
3. Loss of myelin and oligodendrocytes in CNS and peripheral nerves
4. “Globoid cells” (fat macrophages) in brain
5. Onset around 3-6 months. Starts stumbling, cannot swallow.
6. Rapidly progressive muscle stiffness, weakness
7. Spasticity in the hands, hand change

Question 4

B1 (Thiamine) Deficiency

Wernicke encephalopathy

Korsakoff syndrome

Answer 4

Usually associated with chronic alcoholism

Wernicke encephalopathy

• Ataxia, ophthalmoplegia (uncontrolled eye movement), nystagmus, confusion, and impairment of short-term memory
• Hemorrhage and necrosis in mammillary bodies, walls of third and fourth ventricles
• Acute, reversible

Korsakoff syndrome

• Memory disturbances, confabulation (memory invention)
• Cystic spaces (caused by macrophage clearing), hemosiderin-laden macrophages in mammillary bodies, ventricle walls
• Thalamic lesions too
• Prolonged, mostly irreversible

Question 5

B12 (Thiamine) Deficiency

Answer 5

Not due to malnutrtion
Anemia – initial complaint/diagnosis

• Reversible with B12 administration
• Folate will get rid of anemia but not other symptoms

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 6

Abnormal blood sugar

Answer 6

Hypoglycemia

• Most vulnerable: large pyramidal neurons of cortex (“pseudolaminar necrosis”)
• Also vulnerable: hippocampus and cerebellum
• Stupor, nausea (in children)
• Psuedolaminar necrosis

Hyperglycemia

• Most commonly seen in diabetes mellitus
• Can be associated with either ketoacidosis or hyperosmolar coma
• During lipid metabolism, ketone bodies and make and acidify the blood
• Dehydration, confusion, stupor, coma

Question 7

Carbon Monoxide

Answer 7

• Injury due to hypoxia
• Cortex, hippocampus, and Purkinje cells are most vulnerable
• May see demylination of white matter tracts
• Pinkish glow

Question 8

Methanol

Answer 8

• Affects retina
• Degeneration of ganglion cells
• May cause blindness

Question 9

Ethanol

Answer 9

Cerebellar atrophy, loss of granule cells, loss of Purkinje cells, Bergmann gliosis (lots of astrocytes proliferating in the presence of Purkinje cells)