Analysis of β-galactosilceramidase leukocytal in Colombian in patients with suspect clinic of Krabbe disease, a screening of high risk
Abstract
Krabbe disease is a disorder of autosomal recessive sphingolipid metabolism caused by deficiency β-galactosylceramidase (β-Galsil) (EC3.2.1.46), an enzymatic defect that causes a hurt neurodegenerative, muscular hypertonia and Spasticity, convulsions, hearing loss and in 85% of cases early death, among other findings.
The incidence documented for “Krabbe disease” in the United States and Europe is 1:100.000 newborns, but recent studies have shown values greater than 1:22.000 in New York. In Latin America, reports are limited, with reports of high-risk screening in Brazil and isolated cases in Mexico, providing an important underdiagnosis scenario, a situation that is not unknown in Colombia, where there is no literature on the disease.
A study of activity and reference values for β-galactosylceramidase enzyme leukocytal, was then presented to the scientific community, from 259 samples from 110 healthy people and 149 patients with neurodegenerative compromise. The enzymatic evaluation involved two methods (Colorimetric and Fluorometric) that allowed the establishment of a reference range for β-Galsil in Colorimetric technique: 2.04-14.93 nmol/mgprot/h and in fluorometric technique: 0.3-4.21 nmol/mgprot/h. The screening study allowed the identification of a patient with Krabbe disease who presented activity values expressed in nmol/mgprot/h of 1.85 and 0.034, correspondingly to the techniques described above. A final finding that allows to validate the two standardized methods for the diagnosis of the disease and to establish reference values in Colombian population.
Krabbe disease is a disorder of autosomal recessive sphingolipid metabolism caused by deficiency β-galactosylceramidase (β-Galsil) (EC3.2.1.46), an enzymatic defect that causes a hurt neurodegenerative, muscular hypertonia and Spasticity, convulsions, hearing loss and in 85% of cases early death, among other findings.
The incidence documented for “Krabbe disease”in the United States and Europe is 1:100.000 newborns, but recent studies have shown values greater than 1:22.000 in New York. In Latin America, reports are limited, with reports of high-risk screening in Brazil and isolated cases in Mexico, providing an important underdiagnosis scenario, a situation that is not unknown in Colombia, where there is no literature on the disease.
A study of activity and reference values for β-galactosylceramidase enzyme leukocytal, was then presented to the scientific community, from 259 samples from 110 healthy people and 149 patients with neurodegenerative compromise. The enzymatic evaluation involved two methods (Colorimetric and Fluorometric) that allowed the establishment of a reference range for β-Galsil in Colorimetric technique: 2.04-14.93 nmol/mgprot/h and in fluorometric technique: 0.3-4.21 nmol/mgprot/h. The screening study allowed the identification of a patient with Krabbe disease who presented activity values expressed in nmol/mgprot/h of 1.85 and 0.034, correspondingly to the techniques described above. A final finding that allows to validate the two standardized methods for the diagnosis of the disease and to establish reference values in Colombian population.
Downloads
Languages:
esReferences
Schomburg I, Chang A, Schomburg D. Brenda, enzyme data and metabolic information. Nucleic Acids Res., 2002; (30):47-9 https://doi.org/10.1093/nar/30.1.47
Scheer M, Grote A, Chang A, Schomburg I, Munaretto C, Rother M, Sóhngen C, Stelzer M, Thiele J, Schomburg D. BRENDA, the enzyme information system in 2011. Nucleic Acids Res., 2011; (39):670-76. https://doi.org/10.1093/nar/gkq1089
Wenger, D. A., Suzuki, K., Suzuki, Y., and Suzuki, K. Galactosylceramide lipidosis: Globoid cell leukodystrophy (Krabbe disease). En: Valle D, Beaudet A, Vogelstein B, Kinzler K, Antonarakis SE, Ballabio A editors The Metabolic and Molecular Basic of Inherited Disease 8th New York: McGraw-Hill, 2001, p. 3669 - 3694.
Barone R, Brühl K, Stoeter P, Fiumara A, Pavone L, Beck M. Clinical and Neuroradiological Findings in Classic Infantile and Late-Onset Globoid-Cell Leukodystrophy (Krabbe Disease). Am J Med Genet., 1996; (63):209-11. https://doi.org/10.1002/(SICI)1096-8628(19960503)63:1<209::AID-AJMG37>3.0.CO;2-Q
Giri S, Khan M, Rattan R, Singh I, Singh AK. Krabbe disease: psychosine-mediated activation of phospholipase A2 in oligodendrocyte cell death. J Lipid Res., 2006; (47):1478 - 92. https://doi.org/10.1194/jlr.M600084-JLR200
Suzuki K, Suzuki Y. Globoid Cell Leucodystrophy (Krabbe´s Disease). Deficiency of Galactocerebroside B-Galactosidase. Proc Natll Acad Sci., 1970; (66):302-9.
King MW. The Medical Biochemistry [on line] 2012. Avialable in http://themedicalbiochemistrypage.org/index.php
Tappino B, Biacheri R, Mort M, Regis S, Corsolini F, Rossi A, Stroppiano M, Lualdi S, Fiumara A, Bembi B, Di Rocco M, Cooper D, Filocamo M. Identification and characterization of 15 Novel GALC gene mutations causing Krabbe Disease. Hum Mutat., 2010; (31): E1894-E1915. https://doi.org/10.1002/humu.21367
Oehimann, Ralph, Zlotogora, Joel, Wenger, David A., Knowlton, Robert G Localization of the Krabbe Disease Gene (GALC) on chromosome 14 by Multipoint linkage analysis. Am J Hum Genet., 1993; (53):1250-55.
Luzi P, Rafi MA, Wenger DA. Structure and organization of the human galactocerebrosidase (GALC) gene. Genomics., 1995; (26);407-09. https://doi.org/10.1016/0888-7543(95)80230-J
Sakai N, Inui K, Fujii N, Fukushima H, Nishimoto J, Yanagihara I, Isegawa Y, Iwamatsu A, Okada S. Krabbe disease: isolation and characterization of a full-length cDNA for human galactocerebrosidase. Biochem Biophys Res Commun., 1994; (198):485-91. https://doi.org/10.1006/bbrc.1994.1071
Chen YQ, Rafi MA, De Gala G, Wenger DA. Cloning and expression of cDNA encoding human galactocerebrosidase, the enzyme deficient in globoid cell leukodystrophy. Hum Mol Genet., 1993; (2):1841-45. https://doi.org/10.1093/hmg/2.11.1841
Luzi P, Rafi MA, Wenger DA. Multiple mutations in the GALC gene in a patient with adult-onset Krabbe disease. Ann Neurol., 1996; (40):116-19. https://doi.org/10.1002/ana.410400119
Wenger D. Krabbe Disease En Associate editors Pagon RA, Bird TD, Dolan C, Stephens K, and Adam M. GeneReviews [on line] University of Washington (WA) Seattle, 2011. Avialable in www.ncbi.nlm.nih.gov
Duffner PK, Barczykowski A, Kay D, Jalal K, Yan L, Abdelhalim A, Gill S, Gill AL, Carter R. Later Onset Phenotypes of Krabbe Disease: Results of the World-Wide Registry. Pediatric Neurology., 2012; (46):298 - 306. https://doi.org/10.1016/j.pediatrneurol.2012.02.023
Duffner PK, Caggana M, Orsini J, Wenger D, Patterson MC, Crosley CJ, y Others. Newborn Screening for Krabbe Disease: the New York State Model. Pediatr Neurol., 2009; (40):245-52.
Villegas H, Hernández A, Peralta S. Vásquez y Reyes B. Diagnóstico de leucodistrofia de Krabbe por microscopia electrónica de transmisión. Informe de un paciente. Cir Ciruj., 2006; (74):477-81.
Coelho J.C., Waner M., Burin M.G., Vargas C.R., Giugliani R. Selective screening of 10.000 high-risk Brazilian patients for the detection of inborn errors of metabolism. Eur J Pediatr., 1997; (156):650-4. https://doi.org/10.1007/s004310050685
Shapira E, Blitzer MG, Miller JB, Africk DK. Biochemical Genetics. A laboratory manual. New York, Oxford University Press, 1989.
Smith P. K., Krohn, R. I., Hermanson, G. T., Mallia, A. K., Gartner, F. H., Frovenzano, M. D., Fujimoto, E. K., Goeke, N. M., Olson, B. J. y. Klenk, D. C Measurement of Protein Using Bicinchoninic Acid. Annal Biochem., 1985; (150): 76-85.
Besley G, Gatt S. Spectrophotometric and fluorimetric assays of galactocerebrosidase activity, their use in the diagnosis of Krabbe's disease. Clin Chimi Acta., 1981; (110):19-26.
Giles L., Cooper A., Fowler B., Sardharwalla I. B., Donnai P Krabbe Disease: First Trimester Diagnoss confirmed on cultured amniotic fluid cells and fetal tissues. Prenat Diagn., 1987; (7):329-32. https://doi.org/10.1002/pd.1970070506
Wiederschain, G., Raghavan, S. y Kolodny, E Characterization of 6-hexadecanoylamino-4-methylumbelliferyl-D-galactopyranoside as fluorogenic substrate of galactocerebrosidase for the diagnosis of Krabbe disease. Clin Chim Acta., 1992; (205):87-96.
Shapira C, Beaudet A, Sly W, Valle D. The metabolic and molecular bases of inherited disease. 7th edition McGraw Hill 1995; p.2465-94.
Uribe A. Estudio Bioquímico de los desórdenes del metabolismo de los mucopolisacáridos en Colombia. [diseertation] Bogotá - Colombia: Universidad de los Andes., 2002; p.125-127.
Uribe, A., Ayala, A., Espa-a, M., Arevalo, I., Pacheco, N., & Garcia, L. M. J. β-Galactosidase Deficiency in Colombia: Report of 20 Patients Detected Using Dried Blood Spot Samples. Journal of Inborn Errors of Metabolism and Screening., 2015;(3):3- 4
Moses LE, Shapiro D, Littenberg B. Combining independent studies of a diagnostic test into a summary ROC curve: Data-analytic approaches and some additional considerations. Stat Med., 1993; (12):1293 – 1316. https://doi.org/10.1002/sim.4780121403
Burgue-o MJ, Garcia-Bastos JL, Gonzalez-Buitrago JM. Las curvas ROC en la evaluación de las pruebas diagnósticas. Med Clin (Brac)., 1995; (104):661-70.
Uribe A., Espinosa E., Echeverry O., Solano M., Espa-a M., Ayala A. Tamizaje para enfermedades neurodegenerativas. Resultados de cuatro a-os de Investigación. Acta Neurol Colomb., 2002, (18):3-17.
Svennerholm L, Vanier MT, Häkansson G, Mänsson JE. Use of Leukocytes in Diagnosis of Krabbe disease and detection of carriers. Clin Chim Acta., 1981; (112):333-42. https://doi.org/10.1016/0009-8981(81)90456-3
Argumedo, N., Uribe, A. Leukocytary Hexosaminidase Valoration: A Study in Control Population and Individuals with Neurodegenerative Illnesses. Molecular Genetics and Metabolism., 2012; 105(2), S18. https://doi.org/10.1016/j.ymgme.2011.11.019
Krivit W, Shapiro EG, Peters C, Wagner JE, Cornu G, Kurtzberg J, Wenger DA, Kolodny EH. Hematopoietic stem-cell transplantation in globoid-cell leukodystrophy. The New England Journal of Medicine., 1998; (338):1119 - 26. https://doi.org/10.1056/NEJM199804163381605
Neri M, Ricca A, Di Girolamo I, Alcala B, Cavazzini FC, Orlacchio A, Martino S. Naldini L, Gritti A. Neural Stem Cell Gene Therapy Ameliorates Pathology and Function. Stem Cells., 2011; (29):1559 – 71. https://doi.org/10.1002/stem.701
Kondo, Y., Wenger, David A., Gallo, V., y. Duncan, Ian D Galactocerebrosidase deficient oligodendrocytes maintain stable central myelin by exogenous replacement of the missing enzyme in mice. PNAS., 2005; (102):18670 -5. https://doi.org/10.1073/pnas.0506473102
Biswas, Sangita; Le Vine, Steven M. Substrate-reduction therapy enhances the benefits of bone marrow transplantation in young mice with globoid cell leukodystrophy. Pediatric research., 2002; 51(1):40-47. https://doi.org/10.1203/00006450-200201000-00009
Hawkins-Salsbury, J. A., Shea, L., Jiang, X., Hunter, D. A., Guzman, A. M., Reddy, A. S., ... & Sands, M. S. Mechanism-based combination treatment dramatically increases therapeutic efficacy in murine globoid cell leukodystrophy. Journal of Neuroscience., 2015; 35 (16), 6495-6505. https://doi.org/10.1523/JNEUROSCI.4199-14.2015
