title: Compound Galactosylceramidase Gene (GALC) Heterozygosity in a Boy with Infantile Krabbe Disease (KD).
abstract: Krabbe disease (KD) (globoid cell leukodystrophy) is a degenerative, lysosomal storage disease, caused by a severe loss of galactocerebrosidase (GALC) enzymatic activity. The inheritance is autosomal recessive. KD affects the white matter of the central and peripheral nervous systems. We present a 3 year old boy in whom the disease had an 'infantile' or 'classic' presentation, with spasticity, irritability, and developmental delay. In addition the boy showed progressive severe motor and mental deterioration, difficulties in swallowing and decerebration. Molecular analysis revealed that the child is a compound heterozygote: p.Asp187Val (c.560A>T) and p.Ile250Thr (c.749T>C). The father was the carrier of p.Asp187Val (c.560A>T), while the mother was the carrier of the p.Ile250Thr (c.749T>C) in exon 6 of the GALC gene. The clinical course in this compound heterozygote is severe and the patient passed away at the age of 3 years. Genotype-phenotype relations are discussed in this Macedonian patient with KD.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Gucev
authors.forename: Velibor
authors.initials: V
authors.lastname: Tasic
mesh_terms: D002657:Child Development; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005091:Exons; D017809:Fatal Outcome; D005698:Galactosylceramidase / Q000172:deficiency / Q000235:genetics*; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007965:Leukodystrophy, Globoid Cell / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012720:Severity of Illness Index
chemical_list: D005819:Genetic Markers; D005698:Galactosylceramidase