The sphingolipidoses Krabbe disease and metachromatic leukodystrophy are fatal early-onset demyelinating diseases caused by defects in the enzymes β-galactosylceramidase (GALC) and arylsulfatase A (ARSA) that degrade GalCer and sulfatide, respectively (Fig. 1A) (18). The gene discussed is ARSA; the disease is metachromatic leukodystrophy.