Metachromatic Leukodystrophy Workup

Updated: Jan 22, 2021
  • Author: Anna V Blenda, PhD; Chief Editor: Luis O Rohena, MD, MS, FAAP, FACMG  more...
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Workup

Laboratory Studies

Arylsulfatase A (ARSA) enzyme activity may be decreased in leukocytes or cultured skin fibroblasts. Cerebral spinal fluid (CSF) protein levels may be increased (although this finding is nonspecific). The range of values of ARSA activity in the CSF has been established empirically for metachromatic leukodystrophy (MLD) in clinical practice. [30]

Metachromatic leukodystrophy may be distinguished from ARSA pseudodeficiency using one of the following tests:

  • Urine sulfatide level
  • Radiolabeled sulfatide fibroblast loading
  • DNA mutation analysis

Arylsulfatase A activity may be measured to identify carriers and make prenatal diagnoses. This test is available in a few select laboratories. In addition, multiplexed immune-quantification assays have been developed that screen numerous lysosomal proteins. Implementation of this technique in newborn screening (using blood spots) for early identification of lysosomal storage disorders has been shown to be feasible but requires further validation. [31]

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Other Tests

Brain MRI may be performed to identify white matter lesions and atrophy, which are characteristic of metachromatic leukodystrophy but is nonspecific. [32]

The following procedures may be indicated:

Metachromatic granules are found in biopsy specimens from peripheral nerves, the kidney, or the gallbladder. Widespread loss of myelin in the CNS and peripheral nerves may be present.

The following tests may be indicated:

  • Nerve conduction studies

  • Neurocognitive, neuropsychological testing, or both

 

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Procedures

 

 

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Staging

 

Table 1. Characteristics of the 4 Forms of Metachromatic Leukodystrophy (Open Table in a new window)

Form

Age at

Onset

(y)

Inheritance

Pattern

Frequency

Neurocognitive

Deficit

Progression

Effect of Bone

Marrow

Transplantation

Late infantile

< 4

Autosomal recessive

Most common

Motor milestones lost, neurocognitive function lost

Death within 5-6 y

Not helpful in symptomatic patients; may halt cognitive deterioration in asymptomatic patients

Early juvenile

4-6

Autosomal recessive

Less common

Motor milestones lost, learning and behavior impaired

Death within 10-15 y

May be beneficial in symptomatic and asymptomatic patients

Late juvenile

6-16

Autosomal recessive

Rare

Personality changes, behavioral changes, dementia, psychoses, decline in school or work performance

Slow

May be beneficial in asymptomatic or mildly symptomatic patients

Adult

>16

Autosomal recessive

Rare

Personality changes, behavioral changes, dementia, psychoses, decline in school or work performance

Slow

May be beneficial in asymptomatic or mildly symptomatic patients

 

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