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Krabbe disease (globoid cell leukodystrophy) is an autosomal recessive lysosomal storage disorder caused by an enzyme deficiency of galactocerebrosidase (GALC). Krabbe disease is caused by mutations in the GALC gene, and it has an estimated frequency of 1 in 100,000 births.
Eighty-five percent to 90% of patients present before the first year of life with central nervous system impairment including increasing irritability, developmental delay, and sensitivity to stimuli. Rapid neurodegeneration including white matter disease follows with death usually occurring by age 2. Ten percent to 15% of individuals have late onset forms of the disease that are characterized by ataxia, vision loss, weakness, and psychomotor regression presenting anytime from age 6 months to the seventh decade of life. The clinical course of Krabbe disease can be variable, even within the same family. Treatment is mostly supportive, although hematopoietic stem cell transplantation has shown some success if treatment begins before neurologic damage has occurred.
Psychosine (PSY), a neurotoxin at elevated concentrations, is 1 of 4 substrates degraded by galactocerebrosidase. It has been shown to be elevated in patients with active disease and therefore, may be a useful biomarker for the presence of disease or disease progression. PSY measurement in dried blood spots is under study to determine if it is a useful follow-up to an abnormal newborn screen for Krabbe disease.
Reduced or absent galactocerebrosidase in leukocytes (CBGC / Galactocerebrosidase, Leukocytes) or fibroblasts (CBGT / Galactocerebrosidase, Fibroblasts) along with psychosine analysis can indicate a diagnosis of Krabbe disease. Molecular sequencing of the GALC gene (KRABZ / Krabbe Disease, Full Gene Analysis and Large [30 kb] Deletion, PCR) allows for detection of the disease-causing mutations in affected patients and carrier detection in family members.
Quantification of psychosine (galactosylsphingosine) in dried blood spots to support the biochemical diagnosis and follow-up of individuals affected with Krabbe disease
An elevation of psychosine is indicative of symptomatic Krabbe disease.
This test is not capable of identifying Krabbe carriers.
Psychosine levels may be normal in patients who are not yet symptomatic or have late onset Krabbe disease.
Normal <10 nmol/L psychosine
1. Orsini J, Morrissey M, Slavin L, et al: Implementation of newborn screening for Krabbe disease: Population study and cutoff determination. Clin Biochem 2009;42:877-884
2. Svennerholm L, Vanier M, Mansson J: Krabbe disease: a galactosylsphingosine (psychosine) lipidosis. J Lipid Res 1980;21:53-64
3. Enns GM, Steiner RD, Cowan TM: Lysosomal Disorders. In Pediatric Endocrinology and Inborn Errors of Metabolism. Edited by K Sarafoglou, G Hoffman, KS Roth. New York, McGraw-Hill Medical, 2009, p 744
4. Turgeon CT, Orsini JJ, Sanders KA, et al: Measurement of psychosine in dried blood spots - a possible improvement to newborn screening programs for Krabbe disease. J Inherit Metab Dis 2015 Sep;38(5):923-929