inherited neurodegenerative diseases

Question 1

What are the hereditary lysosomal disorders?

Answer 1

Tay-Sachs, Niemann-Pick, Gaucher, Krabbe, metachromatic leukodystrophy, mucopolysaccharidoses, neuronal cord lipofuscinoses

Question 2

What is the metabolic defect in Tay-Sachs?

Answer 2

def. hexosaminidase A (chrom 15)

accumulates GM-2 ganglioside

Question 3

Tay-Sachs clinical characteristics?

Answer 3

• normal development for 4-6 mos
• myoclonic jerks, cherry red macula, floppy baby, hyperreflexia, sz, decortication, macrocephaly
• death by age 3

Question 4

metabolic defect in Niemann-Pick?

Answer 4

def in sphinogmyelinase (chrom 11)
accum sphingomyelin

Question 5

clinical characteristics of Niemann-Pick

Answer 5

• infantile form: regression, dementia, hypotonia, HEPATOMEGALY, cherry red macula, death by age 2
• juvenile form: sz, spasticity, vertical gaze paresis

Question 6

defect in Gaucher?

Answer 6

gluosylceramide B glucosidase (chrom 1)

Question 7

Gaucher characteristics?

Answer 7

infantile: regression, POOR FEEDING, seizures, spasticity, cherry red macula, death by age 2
juvenile: dementia, sz, splenomegaly
adult: splenomegaly, thrombocytopenia

Question 8

Krabbe’s dz defect

Answer 8

galactosylceramide B-galactosidase (chrom 14)

Question 9

Krabbe’s dz characteristics?

Answer 9

infantile: onset age 1-5; irritable, rigid, optic ataxia, gait difficulty, vision loss, cortical blindness, sz, periph neuropathy, prog psychomotor deterioration
mentation often spared
elevated CSF, MRI demylination

Question 10

metachromatic leukodystrophy defect

Answer 10

arylsulfatase a (chrom 22)

Question 11

metachromatic leukodystrophy character?

Answer 11

white matter dz
infantile: 6-24 mo; death in 5-6 years
gait difficulty, hypotonia, ataxia, rapid intellectual deterioration, dementia, cherry red macula, periph neuropathy; HSM, skeletal deformitys
- inc CSF
- pos sulfatide test
- MRI w/ diffuse demyelination sparing subcortical U fibers

Question 12

mucopolysaccharidoses (Hurlers) defect

Answer 12

a-iduronidase (chrom 4)

Question 13

MPS character?

Answer 13

dysmorphic features, skeletal deformities, psychomotor deterioration
- develops w/in 1st year: macroglossia, glaucoma, hypertelorism, abnormal gait, sensorineural deafness