arylsulfatase deficiency type metachromatic leokodystrophy
MIM.250100 22q13.31-qter
Deficiency: Arylsulfatase deficiency is one three allelic types of metachromatic deficiencies.
Clinical synopsis
urinary incontinence
mental deterioration
loss of speech
hypotonia
muscle weakness
hait disturbances
hyporeflexia (early)
dysarthria
dystonia
chorea
ataxia
spastic tetraplegia
hyperreflexia (later)
extensor plantar responses (later)
seizures
bulbar palsies
progression to tetraplegia and decerebrate state
cerebral white matter abnormalities
elevated CSF protein
EMG shows neuropathic changes
delayed nerve conduction velocity
behavioral/psychiatric manifestations
behavioral disturbances
emotional lability
poor school performance
hallucinations
delusions
disorganized thinking
late infantile onset 6-24 months
juvenile onset 4 years to puberty
adult onset after puberty
adult onset form usually presents with psychiatric manifestations
Pathological synopsis
progressive polyneuropathy
demyelination
optic atrophy
gallbladder anomalies
- gallbladder dysfunction
- cholecystitis
- gallbladder papilloma
- villous papilloma of the gallbladder (#6500553#)
golden brown bodies in urinary sediment (#13477349#)
Morphological synopsis
metachromatic deposits (sulfatide-containing) in central and peripheral nervous systems and visceral organs
decreased arylsulfatase A (ARSA) activity in urine, leukocytes, fibroblasts
increased CSF protein
increased urinary sulfatide excretion
Etiology
germline mutations in the arylsulfatase A gene (ARSA) (MIM.607574)
Differential diagnosis
pseudoarylsulfatase A deficiency is an allelic disorder with reduced levels of ARSA activity, but no neurologic manifestations