Diffusion Tensor Imaging (DTI) in Infants With Krabbe Disease

This study is designed to learn about early brain development in children with Krabbe disease
and to use diffusion tensor imaging (DTI) as an early diagnostic tool to differentiate
children with infantile Krabbe disease from newborns who are disease free but have very low
enzyme levels. Additionally, this study will determine how certain structures in the brain
will develop over 24 months in children with infantile Krabbe disease and those without
disease who have low enzyme levels. This study will also reveal information about the
learning and motor development of children, and will help researchers predict outcomes after
treatment.

Krabbe disease is a rare, childhood neurodegenerative disorder caused by galactocerebrosidase
deficiency. It results in rapid demyelination, progressive spasticity, mental deterioration,
blindness, deafness, seizures, and death. Based on previously published findings, treatment
with unrelated umbilical cord blood transplantation is now standard for Krabbe disease,
provided that the treatment occurs within the first weeks of life and before symptoms appear.

Once newborns are identified through population screening, there is no objective measure to
predict if the baby will develop the most frequent rapidly progressive infantile forms of
Krabbe or have a slower juvenile or adult form. Phenotype and genotype correlations are not
possible because there are more than 150 mutations that can cause the disease and many
polymorphisms in the normal population that affect the enzyme level.

There is an urgent clinical need to develop a predictive measure. To date, there are no
available tools to classify infants into the infantile versus later forms. New advances in
neuroimaging techniques have enabled scientists to quantify changes in brain growth and
myelination early in life and before disease symptoms develop.

Knowledge from this study will help identify the window of opportunity for early intervention
and treatment to prevent severe disability, and may lead to better treatment strategies.

Inclusion Criteria:

1. Positive newborn screening test (low galactocerebrosidase)

2. Infantile Krabbe Disease diagnosed by confirmatory low levels of residual enzyme by
Dr. Wenger's Lysosmal Storage Diseases laboratory at Jefferson's Medical College
(contracted by New York State) and/or carrier status established because of family
history of Krabbe Disease. Patients have to be less than 6 weeks old at the time of
the first assessment

3. Children at risk of developing motor disability

Exclusion Criteria:

1. Diagnosis or physical signs of known genetic conditions or syndromes, serious medical
or neurological conditions affecting growth and development (e.g., seizure disorder,
diabetes, congenital heart disease) or sensory impairments such as vision or hearing
loss

2. Children who may have suffered serious perinatal brain damage, children with birth
weights less than 2000 grams and/or gestational ages of less than 34 weeks, or those
with a history of intraventricular hemorrhage

3. Children who may have a contraindication for MRI (pacemaker, vascular stents, metallic
ear tubes, other metal implants or braces).