Leukodystrophies

Question 0

Types of Leukodystrophies

Answer 0

Degenerative, mostly affect white matter
Loss of milestones, cognitive decline, spasticity
Most common: Adrenoleukodystrophy
Lysosomal Storage Disorders:
MLD (metachromatic leukokdystrophy)
GCL (globoid cell leukodystrophy)- aka Krabbe Disease
Causes of macrocephaly: Canavan Disease, Alexander Disease

Question 1

Adrenoleukodystrophy

Answer 1

X-linked, ABCD1 gene
Can’t transport VLCFA into peroxisome
accumulate in myelin, adrenal glands
Present 5-8yo
spasticity, cognitive impairment, seizures
Changes in occipital lobe first, progress anterior
Treatment: Lorenzo’s Oil, BMT

Question 2

Canavan Disease

Answer 2

spongy degeneration of cerebral white matter
autosomal recessive
common in Ashkenazi Jews
causes macrocephaly
diagnosed by elevated N-acetylaspartic acid

Question 3

Alexander Disease

Answer 3

autosomal dominant (usually de novo mutations)
GFAP mutation
causes macrocephaly
changes mostly in frontal region on MRI

Question 4

Pelizaeus-Merzbacher Disease

Answer 4

X-linked
PLP gene deletion/duplication
d/o myelin formation
p/w nystagmus, spasticity