A proposal to consider: sensitivity, specificity and normal range values of the enzymatic deficiency of lysosomal enzymes.

Volume 1, Issue 2, December 2016     |     PP. 323-335      |     PDF (373 K)    |     Pub. Date: January 4, 2017
DOI:    381 Downloads     6842 Views  

Author(s)

María de la Caridad Menéndez-Sainz, Institute of Neurology and Neurosurgery. Calle 29 No 114, e/ D y E. Vedado. CP 10400. Havana, Cuba.
Sergio González-García, Institute of Neurology and Neurosurgery. Calle 29 No 114, e/ D y E. Vedado. CP 10400. Havana, Cuba.
Alina González-Quevedo, Institute of Neurology and Neurosurgery. Calle 29 No 114, e/ D y E. Vedado. CP 10400. Havana, Cuba.
Marisol Peña-Sánchez, Institute of Neurology and Neurosurgery. Calle 29 No 114, e/ D y E. Vedado. CP 10400. Havana, Cuba.
Rebeca Fernández-Carriera, Institute of Neurology and Neurosurgery. Calle 29 No 114, e/ D y E. Vedado. CP 10400. Havana, Cuba.
Anay Cordero-Eiriz, Institute of Neurology and Neurosurgery. Calle 29 No 114, e/ D y E. Vedado. CP 10400. Havana, Cuba.

Abstract
Background. Lysosomal storage diseases (LSD) are a group of more than 50 genetic disorders and demonstrating deficiency of enzyme activity (EA) should be the first step in its diagnosis. Referral for molecular studies when an LSD is suspected is mainly based in the measurement of the percent relative enzyme activity; nevertheless, the great variability observed in healthy subjects can make the decision unreliable, especially when the patient has some degree of residual activity. Objectives. To evaluate the sensitivity and specificity of enzymatic diagnosis in leukocytes and describe normal values of EA in amniocytes and leukocytes. Design and Methods. 16 lysosomal enzymes from leukocytes were studied in 151 LSD patients and 869 apparently healthy subjects. Enzyme activities for 13 LSDs were studied in 72 amniocyte cultures at 13 and 18 days culture (12 suspected LSDs and 60 controls). Results. The EA for lysosomal enzymes were significantly lower in LSD patients than in controls; the sensitivity and specificity of EA for diagnosis of LSD were mainly above 95% in the majority of the diseases. The normal lysosomal EA in amniocytes was reported; 12 prenatal diagnoses assayed resulted negative for LSD. Conclusions.The high sensitivity and specificity of the enzymatic diagnosis of LSDs suggests its utility to identify subjects with the suspicion of LSD. The description of the normal range of 16 lysosomal enzymes in leukocytes and 13 enzymes in amniocytes could be an important source of information for further studies.

Keywords
sensitivityspecifitynormal rangeenzymaticlysosomaldeficiency

Cite this paper
María de la Caridad Menéndez-Sainz, Sergio González-García, Alina González-Quevedo, Marisol Peña-Sánchez, Rebeca Fernández-Carriera, Anay Cordero-Eiriz, A proposal to consider: sensitivity, specificity and normal range values of the enzymatic deficiency of lysosomal enzymes. , SCIREA Journal of Clinical Medicine. Volume 1, Issue 2, December 2016 | PP. 323-335.

References

[ 1 ] Yu RK, Tsai YT, Ariga T, Yanagisawa M. Structures, biosynthesis, and functions of gangliosides—An overview. J Oleo Sci 2011; 60: 537–44.
[ 2 ] FilocamoM, MorroneA. Lysosomal storage disorders: Molecular basis and laboratory testing. Hum Genomics 2011;5:156–69.
[ 3 ] Wenger DA, Coppola S, Liu SL. Lysosomal storage disorders: diagnostic dilemmas and prospects for therapy. Genet Med 2002;4:412-19.
[ 4 ] Wenger DA, Coppola S, Liu SL. Insights into the diagnosis and treatment of lysosomal storage diseases. Arch Neurol2003;60:322-28.
[ 5 ] Wilcox WR. Lysosomal storage disorders: the need for better pediatric recognition and comprehensive care. J Pediatr2004;144:S3-14.
[ 6 ] Winchester B. Lysosomal metabolism of glycoproteins. Glycobiology 2005;15:1R-15R.
[ 7 ] Menéndez MC. Diagnóstico enzimático de las enfermedades de almacenamiento lisosomal: experiencia de 20 años.Tesis en opción al título de Doctor en Ciencias de la Salud. Universidad de Ciencias Médicas de La Habana. 2012. Availablefrom: http://tesis.repo.sld.cu/view/year/2012.html#group_M.
[ 8 ] Gieselmann V. What can cell biology tell us about heterogeneity in lysosomal storage diseases? ActaPædiatrica2005;94:80–6.
[ 9 ] Wenger DA, Louie E. Pseudodeficiencies of arylsulfatase A and galactocerebrosidaseactivities. DevNeurosci 1991;13:216-21.
[ 10 ] Krasnopolskaya KD, Mirenburg TV, Aronovich EL, Lebedeva TV, Odinokova ON, Demina NA, et al. Diagnosis and Prevention of Lysosomal Storage Diseases in Russia. J lnherMetab Dis 1993;16:994-1002.
[ 11 ] Verma R and Babu A. Human chromosomes: Principles and techniques. 2da ed. McGraw-Hill. 1995:72-127.
[ 12 ] Menéndez C, González S, Peña M,Méndez LA, Quiñones O, Diepa N, et al. Diagnóstico prenatal enzimático de enfermedades lisosomales en Cuba. RevEcuatNeurol 2008;17:1-3.
[ 13 ] Declaración de Helsinki de la AMM - Principios éticos para las investigaciones médicas en seres humanos. Cited 2010 Jul(21); Availablefrom: http://www.wma.net/es/
[ 14 ] Galjaard H, Hoogeveen A, de Wit-Verbeek HA, Reuser AJ, Ho MW, Robinson D. Genetic heterogeneity in GM1 gangliosidosis. Nature 1975;257:60-2.
[ 15 ] Alkhayat AH, Kraemer SA, Leipprandt JR, Macek M, Kleijer WJ, Friderici KH. Human beta-mannosidasecDNA characterization and first identification of a mutation associated with human beta-mannosidosis. Hum Mol Genet 1988;7:75-83.
[ 16 ] Hopwood JJ, Morris CP. The mucopolysaccharidoses: Diagnosis, molecular genetics and treatment. Mol BiolMed1990;7:381-404.
[ 17 ] Meikle PJ, Ranieri E, Simonsen H, Rozaklis T, Ramsay SL, Whitfield PD, et al. Newborn screening for lysosomal storage disorders: clinical evaluation of a two-tier strategy. Pediatrics 2004;114:909-16.
[ 18 ] Civallero G, Michelin K, de Mari J, Viapiana M, Burin M, Coelho JC, et al. Twelve different enzyme assays on dried-blood filter paper samples for detection of patients with selected lysosomal storage diseases. ClinChem2006;372:98–102.
[ 19 ] deGasperi R, Raghavan SS, Sosa MG, Kolodny EH, Carrier C, Rubenstein P, et al. Measurements from normal umbilical cord blood of four enzymatic activities: α-L-iduronidase (Hurler), galactocerebrosidase (globoid cell leukodystrophy), arylsulfatase A (metachromatic leukodystrophy), arylsulfatase B (Maroteaux-Lamy). Bone Marrow Transpl 2000;25:541–44.
[ 20 ] Li Y, Scott CR, Chamoles NA, Ghavami A, Pinto BM, Turecek F, et al. Direct Multiplex Assay of Lysosomal Enzymes in Dried Blood Spots for Newborn Screening. ClinChem2004; 50:1785–96.
[ 21 ] Gort L.Analisi molecular de la mucopolisacaridosi I, la mucopolisacaridosi II i la leucodistrofiametacromática en elspacientsespanyols. Utilitat diagnóstica i correlaciógenotip-fenotip. Tesis Doctoral. Instituto de Bioquímica Clínica. 2000. Barcelona. España.
[ 22 ] Lysosomal Storage Disease: Panel Enzyme Activity (13 Enzymes), Leukocytes. Emory Genetics Laboratory. Available from: http://geneticslab.emory.edu
[ 23 ] Mao X, Bigham AW, Mei R, Gutierrez G, Weiss KM, Brutsaert TD, et al. A genome wide admixture mapping panel for Hispanic/Latino populations. Am J Hum Genet 2007;80:1171-78.
[ 24 ] Parra EJ, Marcini A, Akey J, Martinson J, Batzer MA, Cooper R, et al. Estimating African American admixture proportions by use of population-specific alleles. Am J Hum Genet 1998;63:1839-51.
[ 25 ] Cintado A, Companioni O, Nazabal M, Camacho H, Ferrer A, De Cossio ME, et al. Admixture estimates for the population of Havana City. Annals of Human Biology 2009;36:350-60.
[ 26 ] Aboul A, Fateen E. Prenatal diagnosis of Mucopolysaccharidoses: The first Egyptian experience. BratislLekListy 2004;105:291-340.
[ 27 ] Casagrandi CD, Zaldivar T, Nodarse RA, Carballo CS. Algunos aspectos éticos del diagnóstico prenatal, la medicina y terapia fetales. Rev Cubana ObstetGinecol2005;31:0-0.