Krabbe disease: severe neonatal presentation with a family history of multiple sclerosis.
Krabbe disease, also known as globoid cell leukodystrophy, is a rare autosomal recessive disorder caused by a deficiency of a lysosomal enzyme, galactocerebrosidase. This defect prevents normal turnover of the galactolipids and results in progressive demyelination. In the infantile form, symptoms typically present at 3 to 6 months of age with subsequent neurologic deterioration. We report a case with presentation on day 7 of life and rapid progression culminating in death at 10 weeks. Galactocerebrosidase activity was absent in the leukocytes, and a 30 kb deletion in the GALC gene was found. To our knowledge, this is the earliest reported death from Krabbe disease. Several family members have multiple sclerosis, which is also a demyelinating disorder. We propose that the neonatal expression could be an example of complementary gene interaction in which coinheritance of a predisposition to multiple sclerosis led to the unusual early manifestation and rapid course of Krabbe disease in this infant.
Sahai
Inderneel
I
Division of Genetics and metabolism, Harvard Medical School and Children's Hospital, Boston, MA, USA.
Baris
Hagit
H
Kimonis
Virginia
V
Levy
Harvey L
HL
D017809:Fatal Outcome; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases; D007965:Leukodystrophy, Globoid Cell / Q000235:genetics* / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D009103:Multiple Sclerosis / Q000235:genetics*; D010375:Pedigree; D012720:Severity of Illness Index; D014057:Tomography, X-Ray Computed