Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Krabbe disease (globoid cell leukodystrophy) is an autosomal recessive disorder caused by a deficiency of galactocerebrosidase. A deficiency of this enzyme leads to an accumulation of galactosylceramide causing severe demyelination throughout the brain. Krabbe disease is caused by mutations in the GALC gene, and it has an estimated frequency of 1 in 100,000 births.
Severely affected individuals typically present between 3 to 6 months of age with increasing irritability and sensitivity to stimuli. Rapid neurodegeneration including white matter disease follows with death usually occurring by age 2. A small subset of individuals have late onset forms of the disease that are characterized by ataxia, vision loss, weakness, and psychomotor regression presenting anywhere 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.
Reduced or absent galactocerebrosidase in leukocytes or fibroblasts (CBGT/8287,Galactocerebrosidase, Fibroblasts) can indicate a diagnosis of Krabbe disease. Molecular sequencing of the GALC gene (GALCs/60696, 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.
Diagnosis of Krabbe disease
Values below the reference range are consistent with a diagnosis of Krabbe disease.
The upper limit of normal may change with the specific activity of the substrate. Elevated values have no known clinical significance.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Because of the wide range of enzymatic activities observed in carriers and noncarriers, this test is not recommended for carrier detection.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
> or =1.20 nmol/h/mg protein
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Wenger DA: Krabbe Disease. Available from http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=krabbe Reviewed March 29, 2011
2. Enns GM, Steiner RD, Cowan TM: Lysosomal Disorders. In Pediatric Endocrinology and Inborn Errors of Metabolism. Edited by Sarafoglou K, Hoffman G, Roth KS. New York, McGraw- Hill Medical, 2009, p 744