Metachromatic Leukodystrophy Workup

Updated: Aug 21, 2014
  • Author: Alan K Ikeda, MD; Chief Editor: Luis O Rohena, MD, MS, FAAP, FACMG  more...
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Workup

Laboratory Studies

Arylsulfatase A enzyme activity may be decreased in leukocytes or in cultured skin fibroblasts. CSF protein levels may be increased (although this finding is nonspecific).

Metachromatic leukodystrophy (MLD) may be distinguished from arylsulfatase A pseudodeficiency using one of the following tests:

  • Urine sulfatide levels

  • 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. [6]

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Imaging Studies

Brain MRI may be performed to identify white matter lesions and atrophy, which are characteristic of metachromatic leukodystrophy but nonspecific. [7]

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Other Tests

The following tests may be indicated:

  • Nerve conduction studies

  • Neurocognitive, neuropsychological testing, or both

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Procedures

The following procedures may be indicated:

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Histologic Findings

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.

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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 functions 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,

decreased 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,

decreased school or

work performance

Slow

May be beneficial in asymptomatic or mildly symptomatic patients

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