Metachromatic LeukodystrophyNext Topic

Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal lipid storage disorder caused by the deficiency of arylsulfatase A, an enzyme involved in the degradation of sulfatide. This membrane lipid can be found in various cell types, but is present in particularly high concentrations in the myelin of the central and peripheral nervous systems. Deficiency of arylsulfatase A presents with the clinical features outlined in Table 1 and results in the accumulation of sulfatide, leading to progressive demyelination of the central and peripheral nervous systems and premature patient demise.

Affected Organ/System Clinical Feature
Neurologic

Central Nervous System

mental deterioration, loss of speech, hypotonia, muscle weakness, gait disturbances, hyporeflexia (early) dysarthria, dystonia, chorea, ataxia, spastic tetraplegia (later), extensor plantar responses (later), seizures, bulbar palsies, progression to tetraplegia and decerebrate state, cerebral white matter abnormalities, elevated CSF protein

Peripheral Nervous System

progressive polyneuropathy, demyelination, EMG shows neuropathic changes, delayed nerve conduction velocity

Behavioral/psychiatric Manifestations

Behavioral disturbances, emotional lability, poor school performance, hallucinations, delusions, disorganized thinking
Gastrointestinal Gall bladder dysfunction, Cholecystitis
Genitourinary Urinary incontinence
Eyes Optic atrophy
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