Natural History Study of Children With Metachromatic Leukodystrophy

Metachromatic leukodystrophy (MLD) is an inherited, autosomal recessive disorder of lipid
metabolism characterized by deficient activity of the lysosomal enzyme, arylsulfatase A
(ASA). MLD is a rare genetic disease that occurs in most parts of the world. The estimated
overall incidence of the disease in the western world is approximately 1 in 100,000 live
births.

This study is a multicenter, observational, longitudinal study that plans to enroll up to 30
patients with onset of MLD-related signs and symptoms prior to 30 months of age and who are
less than 12 years of age. Patients will participate in this study for approximately 114
weeks (Screening through Follow-up) and will be assessed at defined intervals for disease
status.

Inclusion Criteria:

1. Confirmed diagnosis of MLD by both:

- arylsulfatase A (ASA) deficiency by assay in leukocytes AND

- elevated sulfatide in urine

2. Appearance of the first symptoms of disease at or before 30 months of age.

3. A GMFM-88 total (percent) score greater than or equal to 40 at the screening
examination.

4. The patient is less than 12 years of age at the time of enrollment.

5. The patient and his/her parent or legally authorized representative(s) must have the
ability to comply with the clinical protocol.

6. Patient's parent or legally authorized representative(s) must provide written
informed consent prior to performing any study-related activities. Study-related
activities are any procedures that would not have been performed during normal
management of the patient.

Exclusion Criteria:

1. History of hematopoietic stem cell transplantation.

2. The patient has any known or suspected hypersensitivity to agents used for anesthesia
or is thought to be at an unacceptably high risk for associated potential
complications of airway compromise or other conditions.

3. Any other medical condition, serious intercurrent illness, or extenuating
circumstance that, in the opinion of the Investigator, would preclude participation
in the study.

4. The patient is enrolled in another clinical study that involves the use of any
investigational product (drug or device) within 30 days prior to study enrollment or
at any time during the study.