Rafi et al. (1995) analyzed the GALC gene in 2 patients with infantile Krabbe disease and identified homozygosity for a deletion of exons 11-17 that was found to be associated with a 502C-T transition on the same allele, which they designated '502/del.' The transition was later determined to be a polymorphism. Expression of the 502/del mutation in COS-1 cells resulted in no measurable GALC activity above that in mock-transfected cells. Rafi et al. (1995) studied an additional 46 patients with infantile Krabbe disease and identified 8 who were homozygous for the 502/del allele and 5 who were compound heterozygotes for 502/del allele and a second mutant allele. There were 21 patients who were heterozygous and 1 who was homozygous for the 502 polymorphism in whom the presence of the deletion could not be confirmed, but no patient was found with the deletion who did not carry the 502 polymorphism. Luzi et al. (1995) determined that the deletion is approximately 30 kb starting near the middle of intron 10 and including all of the coding region through exon 17 plus an additional 9 kb. De Gasperi et al. (1996) analyzed the GALC gene in 9 families with late-onset globoid cell leukoencephalopathy and in 1 patient with classic Krabbe disease and found that 5 of the patients were compound heterozygotes for the 30-kb deletion first reported by Rafi et al. (1995) and another mutation in the GALC gene. Kleijer et al. (1997) found that the 30-kb deletion was present in 52% of mutant alleles from 41 Dutch patients with Krabbe disease. Tappino et al. (2010) found the 30-kb deletion in 18% of disease alleles among their cohort of 30 Italian patients. They stated that the 502C-T transition has been renumbered as 550C-T based on the first ATG initiation codon as nucleotide +1. (less)