NeuromuscularLysosomalLysosomal Storage Storage Disorders Disorders Lysosomal Storage StorageDisorders Disorders Lysosomal storage disorders (LSDs) comprise more than 50 metabolic disorders including defects in degradative and Lysosomal Storage Disorders lysosomeLysosomal biogenesis storage disorders and endosome–lysosome (LSDs) comprise more traffic. than LSDs 50 metaboare moslictly disorders autosomal including recessive defects disorders, in degradative with the and exceptionsynthetic enzymes, of mucopolysaccharidosis lysosomal membrane type IIdefects, (MPS II), the also neuronal known cer as oidHunter lipofuscinoses syndrome, (NCLs), and Danon and disordersand Fabry of diseases, whichlysosome exhibit biogenesis X-linked and inheritance. endosome–lysosome traffic. LSDs are mostly autosomal recessive disorders, with the exception of mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, and Danon and Fabry diseases, whichCommon exhibit clinical X-linked features inheritance. of LSDs vary significantly from conditions like Fabry and Gaucher disease type I with more subtle symptoms like angiokeratomas or mild organomegaly to those more obvious on a physical exam, including coarse hairCommon and facies, clinical bone features abnormalities, of LSDs vary organomegaly, significantly from and conditionscentral nervous like Fabrysystem and dysfunction. Gaucher disease The overalltype I incidencewith more of LSDssubtle is symptoms estimated like to angiokeratomasbe 1 in 5,000 births. or mild organomegaly to those more obvious on a physical exam, including coarse hair and facies, bone abnormalities, organomegaly, and central nervous system dysfunction. The overall incidence of LSDsAlthough is estimated each LSD to results be 1 in from 5,000 pathogenic births. variants in a different gene leading to a deficiency of enzyme activity or protein function, LSDs share one common biochemical characteristic: an accumulation of substrates within lysosomes. TheAlthough particular each substratesLSD results stored from pathogenicand the site(s) variants of storage in a differe vary. ntThe gene substrate leading type to a is deficiency used to group of enzyme LSDs into activity the or broadprotein categories function, ofLSDs the share MPSs, one the common lipidoses, biochemical the glycogenoses, characteris the tic:oligosaccharidoses, an accumulation andof substrates the NCLs. withinDespite lysosomes. this categorization,The particular substrates many clinical stored similarities and the aresite(s) observed of storage between vary. groups.The substrate type is used to group LSDs into the broad categories of the MPSs, the lipidoses, the glycogenoses, the oligosaccharidoses, and the NCLs. Despite this Biochemicalcategorization, Testing many fclinicalor Lysosomal similarities Storage are observedDisorders between groups. Clinical and biochemical features continue to be used reliably to assign patients to the general lysosomal storage disorder Biochemical Testing for Lysosomal Storage Disorders category. Biochemical testing is primarily used for screening and monitoring disease progression for these disorders. EGL offersClinical biochemicaland biochemic screeningal featur panelses continue for 12 toLSDs be andused 12 reliably glycoprotein to assign storage patients disorders. to the Separategeneral lysosomal screening storagepanels anddisorder single-analytecategory. Biochemical tests are testing available is forprimarily Gaucher used disease, for screening the mucopolysaccharidoses, and monitoring disease and progression sialic acid forstorage these diseases. disorders. EGL Genetics offers biochemical screening panels for 12 LSDs and 12 glycoprotein storage disorders. Separate screening panels and single-analyteTest Code tests are availableTest Name for Gaucher disease, the Turnaroundmucopolysaccharidoses, Time and sialic acidCPT®**Code(s) storage diseases. Lysosomal Storage Disease: Panel Enzyme LS 7-10 days 82657 (x12), 84155 (x12), 84311 (x12) Test Code Activity (12Test Enzymes), Name Leukocytes Turnaround Time CPT®**Code(s) Lysosomal Storage Disease: Panel Enzyme 2 weeks (GAGs performed Fri 10 am/Oligos 82542 (x1), 82570 (x1), 83864 (x1), BLSDSLS Lysosomal Storage Disorders: Urine Screening 7-10 days 82657 (x12), 84155 (x12), 84311 (x12) Activity (12 Enzymes), Leukocytes performed Fri 3 pm) 84275 (x1), 84375 (x1), 84377 (x1) MPS: GAGs, Quantitative and Qualitative, 2 weeks (GAGs performed Fri 10 am/Oligos 82542 (x1), 82570 (x1), 83864 (x1), BLSDSGA Lysosomal Storage Disorders: Urine Screening 7-10 days 82570 (x1), 83864 (x1), 84375 (x1)8 Urine performed Fri 3 pm) 84275 (x1), 84375 (x1), 84377 (x1) MPS:High GAGs,Resolution Quantitativ Oligosaccharide/Glycane and Qualitative, GAOS 7-10 days 8257082542 ( (x1x1)), ,83864 82570 ( (x1x1)), ,84375 84377 ( (x1x1))8 Profile,Urine Urine High Resolution Oligosaccharide/Glycan BSAUOS Free Sialic Acid, Urine 7-1010 day dayss 82542 82570(x1), 82570 (x1), 84275(x1), 84377 (x1) (x1) Profile, Urine Gaucher Disease: Biomarker Panel (ACE, BSAUBM Free Sialic Acid, Urine 7-1010 day dayss 8216482570 ((x1), 8265784275 ((x2x1) CHITO, TRAP), Serum **CPT® is a registered trademarkGaucher of Disease: the American Biomarker Medical Panel Association. (ACE, BM 7-10 days 82164 (x1), 82657 (x2) *Each analyte may be ordered separately.CHITO, TRAP), Serum **CPT® is a registered trademark of the American Medical Association. References: 1. Boustany RM. Nat Rev Neurol. 2013 Oct;9(10):583-98. 2.References:Fuller M, et al. Epidemiology of lysosomal storage diseases: an overview. In Mehta A, Beck M, Sunder-Plassmaan G, eds. Fabry 1. Disease:Boustany Perspectives RM. Nat Rev from Neurol. 5 Years 2013 of Oct;9(10):583-98. FOS. Oxford: Oxford PharmaGenesis; 2006: Chapter 2. 3.2. HuizingFuller M, M., et Helip-Wooleyal. Epidemiology A., Westbroekof lysosomal W., storage et al. Annu.diseases: Rev. an Genomics overview. Hum. In Me Genet.hta A, 2008 Beck (9): M, 359–386.Sunder-Plassmaan G, eds. Fabry 4. OMIM.Disease: Perspectives from 5 Years of FOS. Oxford: Oxford PharmaGenesis; 2006: Chapter 2. 3. Huizing M., Helip-Wooley A., Westbroek W., et al. Annu. Rev. Genomics Hum. Genet. 2008 (9): 359–386. 4. OMIM. For more information about EGL Genetics and the nearly 1000 tests we offer: CALL WEB 470.378.2200 eglgenetics.com Lysosomal Storage Disorders NeuromuscularLysosomal Storage Disorders Disorders MolecularLysosomal Testing Storagefor Lysosomal DisordersStorage Disorders The identification of the precise genetic defect is important for carrier testing and early prenatal diagnosis. Molecular Molecular Testing for Lysosomal Storage Disorders Molecularanalysis is likely Testing to expand for Lysosomalthe clinical spectrum Storage of Disorders LSDs and may also provide data relevant to prognosis and future therapeuticThe identification intervention. of the preciseThe Lysosomal genetic Storage defect is Disorder important Panel for is carrierindicated testing for individuals and early withprenatal abnormal diagnosis. biochemical Molecular The identification of the precise genetic defect is important for carrier testing and early prenatal diagnosis. Molecular resultsanalysis suggestive is likely to expandof an LSD, the clinical clinical features spectrum associated of LSDs and with may LSDs, also and/or provide suspicion data relevant of an neuronalto prognosis ceroid-lipofuscinoses and future analysis is likely to expand the clinical spectrum of LSDs and may also provide data relevant to prognosis and future (NCL).therapeutic intervention. The Lysosomal Storage Disorder Panel is indicated for individuals with abnormal biochemical therapeutic intervention. The Lysosomal Storage Disorder Panel is indicated for individuals with abnormal biochemical results suggestive of an LSD, clinical features associated with LSDs, and/or suspicion of an neuronal ceroid-lipofuscinoses results suggestive of an LSD, clinical features associated with LSDs, and/or suspicion of an neuronal ceroid-lipofuscinoses (NCL). (NCL). Genes Included on Lysosomal Storage Disorders Panel* ADAMTS10 CLN5 GenesFBN1 Included onGLB1 Lysosomal StorageGUSB DisordersKCTD7 Panel* MFSD8 PSAP Genes Included on Lysosomal Storage Disorders Panel* AGA CLN6 FUCA1 GM2A HEXA LAMP2 NAGA SGSH ADAMTS10 CLN5 FBN1 GLB1 GUSB KCTD7 MFSD8 PSAP ADAMTS10ARSA CLN5CLN8 FBN1GAA GLB1GNE GUSBHEXB KCTD7LIPA MFSD8NAGLU SLC17A5PSAP AGA CLN6 FUCA1 GM2A HEXA LAMP2 NAGA SGSH ARSBAGA CTNSCLN6 FUCA1GALC GNPTABGM2A HGSNATHEXA LAMP2LTBP2 NAGANEU1 SMPD1SGSH ARSA CLN8 GAA GNE HEXB LIPA NAGLU SLC17A5 ASAH1ARSA CLN8CTSA GALNSGAA GNPTGGNE HYAL1HEXB MAN2B1LIPA NAGLUNPC1 SLC17A5SUMF1 ARSB CTNS GALC GNPTAB HGSNAT LTBP2 NEU1 SMPD1 ATP13A2ARSB CTNSCTSD GALCGBA GNPTABGNS HGSNATIDS MANBALTBP2 NEU1NPC2 SMPD1TPP1 ASAH1 CTSA GALNS GNPTG HYAL1 MAN2B1 NPC1 SUMF1 ASAH1CLN3 DNAJC5CTSA GALNSGLA GNPTGGRN HYAL1IDUA MAN2B1MCOLN1 NPC1PPT1 SUMF1 ATP13A2 CTSD GBA GNS IDS MANBA NPC2 TPP1 *PleaseATP13A2 note that deletion/duplicationCTSD analysis GBAis available for all genes,GNS with the exceptionIDS of GBA. Some MANBAgenes on this panel areNPC2 associated with additionalTPP1 phenotypes.CLN3 All genes on DNAJC5the next generation sequencingGLA panel may beGRN ordered separately.IDUA Genes included onMCOLN1 panels are subject toPPT1 change. CLN3 DNAJC5 GLA GRN IDUA MCOLN1 PPT1 *Please note that deletion/duplication analysis is available for all genes, with the exception of GBA. Some genes on this panel are associated with additional Some genes on this panel are associated with additional phenotypes. All genes on the next generation