TN 16 (03-18)

DI 23022.235 Metachromatic Leukodystrophy (MLD)




Metachromatic leukodystrophy (MLD) is a hereditary degenerative disease transmitted as an autosomal recessive, due to sulfatase A deficiency, with excess accumulation of sulfated lipids responsible for metachromasia in various tissues. MLD impairs the growth or development of the myelin sheath, the fatty covering that acts as an insulator around nerve fibers
Late infantile form, which is the most common MLD, usually begins in the second year of life (ranges 1-3 years). After normal early development, the infant displays irritability and an unstable walk. Developmental milestones, such as language development, are not met, and muscle wasting eventually gives way to spastic movements, then profound weakness. Seizures usually occur, followed by paralysis and dementia. Children may become comatose.


Arylsulfatase A Deficiency (ARSA), Cerebroside Sulfatase Deficiency, Metachromatic Form of Diffuse Cerebral Sclerosis, Metachromatic Leukoencephalopathy, Scholz-Bielchowsky-Henneberg Diffuse Cerebral Sclerosis, Scholz-Greenfield Disease, Sulphatide Lipidosis, Sulphatidosis, Van Bogaert-Nijssen Disease


Diagnosis of MLD includes MRI to identify lesions and atrophy in the white matter of the brain that is characteristic of MLD. Urine tests usually show elevated sulfatide levels. Some psychiatric disorders coupled with difficulty walking or muscle wasting suggests the possibility of MLD. Blood testing can show a reduced activity of the ARSA enzyme.
Deficiency of the ARSA enzyme alone is not proof of MLD, because a substantial ARSA deficiency without any symptoms or clinical consequences is frequent in the general population. During diagnosis and genetic counseling, these harmless ARSA enzyme deficiencies must be distinguished from those causing MLD. The only diagnostic test that solves this problem and is definitive for MLD diagnosis is analysis of the genetic mutation.


No effective treatment is available to reverse the course of MLD. Drug therapy is part of supportive care for symptoms such as behavioral disturbances, feeding difficulties, seizures, and constipation. Bone marrow transplantation has been tried and there is evidence that this treatment might slow the progression of the disease. In infants, during a symptom-free phase of the late infantile form, neurocognitive function may be stabilized, but the symptoms of motor function loss progress.


The prognosis for MLD is poor. In young children with MLD late infantile form, progressive loss of motor and cognitive functions is rapid. Death usually results within five years after the onset of clinical symptoms.


Suggested MER for Evaluation: Genetic testing of ARSA gene (targeted mutation or sequence analysis, elevation of sulfatides (10 to 100 times normal) in 24-hour urine, enzyme assay for ARSA enzyme activity, MRI or CAT scan with characteristic white matter abnormalities and description of associated clinical findings (muscle weakness or wasting, rigidity developmental delays).

Suggested Listings for Evaluation:




Meets Listing


Late infantile form of MLD confirmed by genetic testing or elevated sulfatides in 24-hour urine.




Medical Equals



* Adjudicators may, at their discretion, use the Medical Evidence of Record or Listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.

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DI 23022.235 - Metachromatic Leukodystrophy (MLD) - 03/28/2018
Batch run: 03/28/2018