Lysosomal Disorders and Mucopolysaccharidosis Panel
Test code: ME1501
The Blueprint Genetics Lysosomal Disorders and Mucopolysaccharidosis Panel is a 99 gene test for genetic diagnostics of patients with clinical suspicion of glycoprotein storage disorders, lipid storage disorders, lysosomal storage diseases (LSDs), mucolipidoses or mucopolysaccharidoses.
Lysosomal storage diseases (LSDs) comprise about 50 unique monogenic autosomal or X-linked diseases. This panel provides effective differential diagnosis and is also part of Comprehensive Metabolism Panel.
About Lysosomal Disorders and Mucopolysaccharidosis
About fifty different lysosomal storage diseases (LSDs) have been identified, including different types of disorders caused by genetic mutations that result in deficiency or reduced activity of native intracellular enzymes that catabolize biological macromolecules. Usually lysosomal storage disorders are caused by lysosomal dysfunction as a consequence of deficiency of a single enzyme required for the metabolism of lipids, glycoproteins or mucopolysaccharides. These enzyme defects result in accumulation of specific macromolecular compounds within lysosomes in various tissues and organs, causing progressive damage that can become life-threatening in some diseases. Although each LSD is individually rare, as a group they have an incidence of about 1/7,000-8,000 live births, varying between different populations. LSDs may be variably expressed as infantile, juvenile, or adult forms. In adult-onset diseases, the pathogenesis is usually slower than in the infantile or juvenile forms, and may include peripheral and CNS symptoms, whereas infantile and juvenile forms often involve progressive central nervous system involvement in addition to peripheral symptoms. In ultimate expression, LSDs show substantial heterogeneity in disease manifestation. Symptomatic pathology may be a function of mutation type and residual enzyme levels and specific mutations or types of mutations may be connected to discrete disease effects even if genotype-phenotype correlations are not strong. Most of LSDs are autosomal recessively inherited such as Niemann-Pick disease, type C, however a few are X-linked recessively inherited, such as Fabry disease and Hunter syndrome (MPS2). Other examples of LSDs covered by this panel are Gaucher's disease (the most common LSD), Tay-Sachs disease, Type II Pompe Disease, Salla disease, Krabbe disease and Hurler disease. Enzyme-replacement therapy (ERT) is now commercially available for six LSDs, typically used lifelong with traditional management practices for each.
Results in 3-4 weeks. We do not offer a maternal cell contamination (MCC) test at the moment. We offer prenatal testing only for cases where the maternal cell contamination studies (MCC) are done by a local genetic laboratory. Read more.
|ABCC8||Hyperinsulinemic hypoglycemia, Diabetes, permanent neonatal, Hypoglycemia, leucine-induced, Diabetes mellitus, transient neonatal||AD/AR||78||601|
|ACY1||Aminoacylase 1 deficiency||AR||5||13|
|ALDH5A1||Succinic semialdehyde dehydrogenase deficiency||AR||8||67|
|ANTXR2||Hyalinosis, infantile systemic, Fibromatosis, juveline hyaline||AR||13||40|
|ASAH1||Spinal muscular atrophy with progressive myoclonic epilepsy, Farber lipogranulomatosis||AR||11||53|
|ASPA||Aspartoacylase deficiency (Canavan disease)||AR||19||90|
|ATP13A2||Parkinson disease (Kufor-Rakeb syndrome)||AR||11||35|
|CLN3||Ceroid lipofuscinosis, neuronal||AR||69||64|
|CLN5||Ceroid lipofuscinosis, neuronal||AR||40||42|
|CLN6||Ceroid lipofuscinosis, neuronal||AR||21||80|
|CLN8||Ceroid lipofuscinosis, neuronal||AR||31||35|
|COL2A1||Avascular necrosis of femoral head, Rhegmatogenous retinal detachment, Epiphyseal dysplasia, with myopia and deafness, Czech dysplasia, Achondrogenesis type 2, Platyspondylic dysplasia Torrance type, Hypochondrogenesis, Spondyloepiphyseal dysplasia congenital (SEDC), Spondyloepimetaphyseal dysplasia (SEMD) Strudwick type, Kniest dysplasia, Spondyloperipheral dysplasia, Mild SED with premature onset arthrosis, SED with metatarsal shortening, Stickler syndrome type 1||AD||106||537|
|COL11A2||Weissenbacher-Zweymuller syndrome, Deafness, Otospondylomegaepiphyseal dysplasia, Fibrochondrogenesis, Stickler syndrome type 3 (non-ocular)||AD/AR||17||51|
|CTSC||Periodontitis, juvenile, Haim-Munk syndrome, Papillon-Lefevre syndrome||AR||15||91|
|CTSD||Ceroid lipofuscinosis, neuronal||AR||11||15|
|DYM||Dyggve-Melchior-Clausen dysplasia, Smith-McCort dysplasia||AR||20||28|
|ETFA||Glutaric aciduria, Multiple acyl-CoA dehydrogenase deficiency||AR||7||28|
|ETFB||Glutaric aciduria, Multiple acyl-CoA dehydrogenase deficiency||AR||7||13|
|ETFDH||Glutaric aciduria, Multiple acyl-CoA dehydrogenase deficiency||AR||36||168|
|FH||Hereditary leiomyomatosis and renal cell cancer||AD||89||161|
|FOLR1||Cerebral folate deficiency||AR||4||24|
|GAA||Glycogen storage disease||AR||79||503|
|GALNS||Mucopolysaccharidosis (Morquio syndrome)||AR||38||328|
|GAMT||Guanidinoacetate methyltransferase deficiency||AR||12||53|
|GLB1||GM1-gangliosidosis, Mucopolysaccharidosis (Morquio syndrome)||AR||53||211|
|GNE||Inclusion body myopathy, Nonaka myopathy, Sialuria||AD/AR||32||193|
|GNS||Mucopolysaccharidosis (Sanfilippo syndrome)||AR||6||25|
|HEXA||Tay-Sachs disease, GM2-gangliosidosis, Hexosaminidase A deficiency||AR||69||182|
|HGSNAT||Mucopolysaccharidosis (Sanfilippo syndrome), Retinitis pigmentosa||AR||17||66|
|HRAS||Costello syndrome, Congenital myopathy with excess of muscle spindles||AD||30||26|
|LAMA2||Muscular dystrophy, congenital merosin-deficient, Schizophrenia||AD/AR||72||225|
|LDB3||Dilated cardiomyopathy (DCM), Myopathy, myofibrillar||AD||10||11|
|LIPA||Wolman disease, Cholesterol ester storage disease||AR||11||59|
|MFSD8||Ceroid lipofuscinosis, neuronal||AR||19||41|
|MOCS1||Molybdenum cofactor deficiency||AR||7||32|
|MOCS2||Molybdenum cofactor deficiency||AR||8||12|
|NAGLU||Mucopolysaccharidosis (Sanfilippo syndrome)||AR||25||156|
|PEX3||Zellweger syndrome, Peroxisome biogenesis disorder||AR||2||7|
|PEX5||Adrenoleukodystrophy, neonatal, Rhizomelic chondrodysplasia punctata, Zellweger syndrome, Peroxisome biogenesis disorder||AR||4||14|
|PEX10||Adrenoleukodystrophy, neonatal, Zellweger syndrome, Peroxisome biogenesis disorder, Ataxia||AR||17||29|
|PEX12||Zellweger syndrome, Peroxisome biogenesis disorder||AR||15||34|
|PEX13||Adrenoleukodystrophy, neonatal, Zellweger syndrome, Peroxisome biogenesis disorder||AR||4||10|
|PEX16||Zellweger syndrome, Peroxisome biogenesis disorder||AR||6||11|
|PEX26||Adrenoleukodystrophy, neonatal, Zellweger syndrome, Peroxisome biogenesis disorder||AR||10||23|
|PGK1||Phosphoglycerate kinase 1 deficiency||XL||14||26|
|PPT1||Ceroid lipofuscinosis, neuronal||AR||72||77|
|PSAP||Krabbe disease, atypical, Metachromatic leukodystrophy due to saposin-b deficiency, Combined saposin deficiency, Gaucher disease, atypical, due to saposin C deficiency||AR||15||24|
|SGSH||Mucopolysaccharidosis (Sanfilippo syndrome)||AR||19||143|
|SLC17A5||Sialuria, Finnish (Salla disease), Infantile sialic acid storage disorder||AR||22||33|
|SUMF1||Multiple sulfatase deficiency||AR||18||51|
|TCF4||Corneal dystrophy, Fuchs endothelial, Pitt-Hopkins syndrome||AD||51||129|
|TPP1||Ceroid lipofuscinosis, neuronal, Spinocerebellar ataxia||AR||33||109|
- * Some regions of the gene are duplicated in the genome leading to limited sensitivity within the regions. Thus, low-quality variants are filtered out from the duplicated regions and only high-quality variants confirmed by other methods are reported out. Read more.
Gene, refers to HGNC approved gene symbol; Inheritance to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL); ClinVar, refers to a number of variants in the gene classified as pathogenic or likely pathogenic in ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/); HGMD, refers to a number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD, http://www.hgmd.cf.ac.uk/ac/). The list of associated (gene specific) phenotypes are generated from CDG (http://research.nhgri.nih.gov/CGD/) or Orphanet (http://www.orpha.net/) databases.
Blueprint Genetics offers a comprehensive lysosomal disorders and mucopolysaccharidosis panel that covers classical genes associated with glycoprotein storage disorders, lipid storage disorders, lysosomal storage diseases (LSDs), mucolipidoses and mucopolysaccharidoses. The genes are carefully selected based on the existing scientific evidence, our experience and most current mutation databases. Candidate genes are excluded from this first-line diagnostic test. The test does not recognise balanced translocations or complex inversions, and it may not detect low-level mosaicism. The test should not be used for analysis of sequence repeats or for diagnosis of disorders caused by mutations in the mitochondrial DNA.
Please see our latest validation report showing sensitivity and specificity for SNPs and indels, sequencing depth, % of the nucleotides reached at least 15x coverage etc. If the Panel is not present in the report, data will be published when the Panel becomes available for ordering. Analytical validation is a continuous process at Blueprint Genetics. Our mission is to improve the quality of the sequencing process and each modification is followed by our standardized validation process. All the Panels available for ordering have sensitivity and specificity higher than > 0.99 to detect single nucleotide polymorphisms and a high sensitivity for indels ranging 1-19 bp. The diagnostic yield varies substantially depending on the used assay, referring healthcare professional, hospital and country. Blueprint Genetics’ Plus Analysis (Seq+Del/Dup) maximizes the chance to find molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be cost-effective first line test if your patient’s phenotype is suggestive for a specific mutation profile. Detection limit for Del/Dup analysis varies through the genome from one to six exon Del/Dups depending on exon size, sequencing coverage and sequence content.
The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. The highest relevance in the reported variants is achieved through elimination of false positive findings based on variability data for thousands of publicly available human reference sequences and validation against our in-house curated mutation database as well as the most current and relevant human mutation databases. Reference databases currently used are the 1000 Genomes Project (http://www.1000genomes.org), the NHLBI GO Exome Sequencing Project (ESP; http://evs.gs.washington.edu/EVS), the Exome Aggregation Consortium (ExAC; http://exac.broadinstitute.org), ClinVar database of genotype-phenotype associations (http://www.ncbi.nlm.nih.gov/clinvar) and the Human Gene Mutation Database (http://www.hgmd.cf.ac.uk). The consequence of variants in coding and splice regions are estimated using the following in silico variant prediction tools: SIFT (http://sift.jcvi.org), Polyphen (http://genetics.bwh.harvard.edu/pph2/), and Mutation Taster (http://www.mutationtaster.org).
Through our online ordering and statement reporting system, Nucleus, the customer can access specific details of the analysis of the patient. This includes coverage and quality specifications and other relevant information on the analysis. This represents our mission to build fully transparent diagnostics where the customer gains easy access to crucial details of the analysis process.
In addition to our cutting-edge patented sequencing technology and proprietary bioinformatics pipeline, we also provide the customers with the best-informed clinical report on the market. Clinical interpretation requires fundamental clinical and genetic understanding. At Blueprint Genetics our geneticists and clinicians, who together evaluate the results from the sequence analysis pipeline in the context of phenotype information provided in the requisition form, prepare the clinical statement. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals, even without training in genetics.
Variants reported in the statement are always classified using the Blueprint Genetics Variant Classification Scheme modified from the ACMG guidelines (Richards et al. 2015), which has been developed by evaluating existing literature, databases and with thousands of clinical cases analyzed in our laboratory. Variant classification forms the corner stone of clinical interpretation and following patient management decisions. Our statement also includes allele frequencies in reference populations and in silico predictions. We also provide PubMed IDs to the articles or submission numbers to public databases that have been used in the interpretation of the detected variants. In our conclusion, we summarize all the existing information and provide our rationale for the classification of the variant.
A final component of the analysis is the Sanger confirmation of the variants classified as likely pathogenic or pathogenic. This does not only bring confidence to the results obtained by our NGS solution but establishes the mutation specific test for family members. Sanger sequencing is also used occasionally with other variants reported in the statement. In the case of variant of uncertain significance (VUS) we do not recommend risk stratification based on the genetic finding. Furthermore, in the case VUS we do not recommend use of genetic information in patient management or genetic counseling. For some cases Blueprint Genetics offers a special free of charge service to investigate the role of identified VUS.
We constantly follow genetic literature adapting new relevant information and findings to our diagnostics. Relevant novel discoveries can be rapidly translated and adopted into our diagnostics without delay. These processes ensure that our diagnostic panels and clinical statements remain the most up-to-date on the market.
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ICD & CPT codes
Commonly used ICD-10 codes when ordering the Lysosomal Disorders and Mucopolysaccharidosis Panel
|E75||Lipid storage disorders|
|E77||Glycoprotein storage disorders|
Accepted sample types
- EDTA blood, min. 1 ml
- Purified DNA, min. 5μg
- Saliva (Oragene DNA OG-500 kit)
Label the sample tube with your patient’s name, date of birth and the date of sample collection.
Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue.