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arylsulfatase deficiency type metachromatic leokodystrophy

MIM.250100 22q13.31-qter

Thursday 29 November 2007

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