by Alexander Kurz
Krabbe disease is an autosomal recessive disorder involving the white matter of the central and peripheral nervous system. The disease is caused by a deficiency of the enzyme beta-galactocerebrosidase. While most patients develop the disease within the first 6 months of life, others develop the disease later in life, including in adulthood.
Globoid cell leukodystrophy
Symptoms and course
Adults patients may show unsteadiness of gait, weakness of the legs postural tremor, limb paresis, and hyperreflexia.
Causes and risk factors
The major biochemical defect is a deficiency of the enzyme beta-galactocerebrosidase beta-galatosidase caused by mutations in the gene encoding the enzyme (14q31).
The MRI may demonstrate changes of demyelination in the white matter of the brain, while nerve conduction can be normal. The diagnosis is established by demonstrating the deficiency of galactosylceramide beta-galactosidase in serum, white blood cells and fibroblasts. Skin biopsy shows typical sprage of galactocerebroside in globoid cells, in eccrise galnds, and in Schwann cells.
Care and treatment
Hematopoietic stem cell transplantation has been tried in Krabbe disease with positive results.
- Andrews, J. M.; Cancilla, P. A.; Grippo, J.; Menkes, J. H. : Globoid cell leukodystrophy (Krabbe's disease): morphological and biochemical studies. Neurology 21: 337-352, 1971
- D'Agostino, A. N.; Sayre, G. P.; Hayles, A. B. : Krabbe's disease: globoid cell type of leukodystrophy. Arch. Neurol. 8: 82-96, 1963
- Krabbe, K. : A new familial infantile form of diffuse brain-sclerosis. Brain 39: 74-114, 1916
- Krivit, W.; Shapiro, E. G.; Peters, C.; Wagner, J. E.; Cornu, G.; Kurtzberg, J.; Wenger, D. A.; Kolodny, E. H.; Vanier, M. T.; Loes, D. J.; Dusenbery, K.; Lockman, L. A. : Hematopoietic stem-cell transplantation in globoid-cell leukodystrophy. New Eng. J. Med. 338: 1119-1126, 1998
- Lyon, G.; Hagberg, B.; Evrard, P.; Allaire, C.; Pavone, L.; Vanier, M. : Symptomatology of late onset Krabbe's leukodystrophy: the European experience. Dev. Neurosci. 13: 240-244, 1991
- Nelson, E.; Aurebeck, G.; Osterberg, K.; Berry, J.; Jabbour, J. T.; Bornhofen, J. : Ultrastructural and chemical studies on Krabbe's disease. J. Neuropath. Exp. Neurol. 22: 414-434, 1963
- Wenger, D. A.; Sattler, M.; Hiatt, W. : Globoid cell leukodystrophy: deficiency of lactosyl ceramide beta-galactosidase. Proc. Nat. Acad. Sci. 71: 854-857, 1974
- Wenger, D. A.; Rafi, M. A.; Luzi, P. : Molecular genetics of Krabbe disease (globoid cell leukodystrophy): diagnostic and clinical implications. Hum. Mutat. 10: 268-279, 1997
Last Updated: vendredi 09 octobre 2009