HSCT for High Risk Inherited Inborn Errors

Inclusion Criteria:

• Adrenoleukodystrophy: Patients from 0-55 years of age diagnosed with ALD as determinedby very long chain fatty acid testing will be eligible for this protocol if they haveevidence of cerebral or cerebellar disease based on MRI testing, AND they aredetermined high risk for any of the following reasons:

1. Age >18 years

2. MRI score >10

3. Evidence of aggressive disease that in the judgment of the Inherited Metabolicand Storage Disease group is sufficiently concerning to consider transplantationwith a reduced intensity regimen instead of a standard full preparative regimen.

• Metachromatic Leukodystrophy: Patients from 0-55 years of age diagnosed with MLD asdetermined by determinations of arylsulfatase A testing will be eligible for thisprotocol IF they are determined high risk for any of the following reasons:

1. Age >18 years

2. Symptomatic disease, as based on neurologic examination, or evidence ofdeterioration based on subsequent neuropsychologic evaluations.

3. Evidence of aggressive disease such as rapidly changing MRI determinations thatin the judgment of the Inherited Metabolic and Storage Disease group issufficiently concerning to consider transplantation with a reduced intensityregimen instead of a standard full preparative regimen.

• Globoid Cell Leukodystrophy: Patients from 0-55 years of age diagnosed with GLD asdetermined by determinations of galactocerebrosidase testing will be eligible for thisprotocol IF they are determined high risk for any of the following reasons:

1. Age >18 years

2. Symptomatic disease, as based on neurologic examination, or evidence ofdeterioration based on subsequent neuropsychologic evaluations.

3. Evidence of aggressive disease such as rapidly changing MRI determinations thatin the judgment of the Inherited Metabolic and Storage Disease group issufficiently concerning to consider transplantation with a reduced intensityregimen instead of a standard full preparative regimen.

• Patients with GM1 gangliosidosis, Tay Sachs disease, Sanfilippo syndrome, Wolmandisease or Sandhoff disease or other inherited metabolic diseases including but notlimited to I-cell disease (mucolipidosis II) who are determined to be sufficientlyadvanced or high risk based on the following reasons:

1. Symptomatic disease, as based on neurologic examination, or evidence ofdeterioration based on subsequent neuropsychologic evaluations.

2. Evidence of an expected poor outcome based on genetic testing or a prior familyhistory of aggressive disease.

3. Other metabolic disorders, including but not limited to I-cell disease, that aredeemed to be high-risk for a poor outcome with a standard transplant regimen dueto anticipated toxicity based on experience gained at the University of Minnesotaor other centers.

Exclusion criteria:

• Major organ dysfunction.

• Advanced Disease Exclusion: Following evaluation, if a consensus of the members of theInherited Metabolic and Storage Disease Program is that a patient is too advanced tobenefit in a measurable and meaningful way from transplant, this will be communicatedto the family, and transplant will not be offered. Measures to assist in thosedeterminations may include: neurologic/neurocognitive functions such as activities ofdaily living, motor function, vision, hearing, interaction with environment,toileting, swallowing, or other standardized measures