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Pathophysiology And Treatment Of Murine Globoid Cell Leukodystrophy, Yedda Li

Arts & Sciences Electronic Theses and Dissertations

Infantile globoid cell leukodystrophy (GLD, Krabbe disease) is a rapidly progressing, invariably fatal pediatric disorder first described in 1916. Krabbe disease is caused by a deficiency in the lysosomal enzyme, galactosylceramidase (GALC), and is characterized clinically by failure to thrive, limb stiffness, seizures, developmental regression, and death by 2-4 years of age. Galactosylceramidase degrades the cytotoxic glycolipid, galactosylsphingosine (psychosine). In the absence of GALC activity, psychosine accumulates primarily in oligodendrocytes and Schwann cells, resulting in profound demyelination. In 1972, psychosine was hypothesized to be responsible for the clinical signs associated with Krabbe disease. However, the ‘Psychosine Hypothesis’ has never been …