Management Guidelines

Clinical practice guidelines for arylsulfatase A deficiency (also known as metachromatic leukodystrophy or MLD) have been published (full text).

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with MLD, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 3.

Arylsulfatase A Deficiency: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Neurologic

| • Neurologic eval

• Measurement of arylsulfatase A enzyme activity

• Measurement of urinary sulfatide excretion

• Brain MRI to assess myelin integrity

• EEG if concern for seizures

• Peripheral nervous system eval, such as nerve conduction studies, can be used to monitor disease progression or responses in therapeutic trials.

• BAERs can be used to assess progression in late-infantile MLD.

| To assess disease progression evaluate need for possible intervention

Referral for HSCT eval, either allogeneic HSCT (US) or autologous gene-modified HSCT (EU UK), preferably at institution w/expertise in allogenic HSCT in persons w/metabolic disorders | For those identified presymptomatically or predicted to have late-onset MLD (For more specific criteria see .)

Development

| Developmental assessment | • To assess disease progression

• To incl motor, adaptive, cognitive, speech-language eval

• Eval for early intervention/ special education

Neurobehavioral/

Psychiatric

| Neuropsychiatric eval | For persons a...

Source: GeneReviews — "Arylsulfatase A Deficiency"

Clinical Guidance

While environmental factors are thought to influence the onset and severity of MLD manifestations, no specific exacerbating agents are known. Initial symptoms are often noted following a febrile illness or other stress, but it is unclear if a high fever accelerates progression. Excessive alcohol and drug use are often associated with later-onset MLD, but it is unclear if this is caused by the disease or is simply an attempt at self-medication in the face of increasing cognitive difficulties .

Source: GeneReviews — "Arylsulfatase A Deficiency"

Therapies Under Investigation

In vivo gene therapy. Allogeneic HSCT and autologous HSCT with gene-corrected cells is showing great benefit, primarily in presymptomatic individuals. These are promising therapies for individuals identified at presymptomatic stages with a family history of MLD or perhaps individuals identified on future newborn screening. Unfortunately, most individuals diagnosed with MLD have no family history of MLD. Hence, most children with severe forms of MLD would not be diagnosed at the presymptomatic phase of the disease, making it unlikely for this therapeutic option to be offered or effective for many individuals with MLD. Accordingly, there is a need for therapies that can get to the brain quickly.

Source: GeneReviews — "Arylsulfatase A Deficiency"