Metabolic Epilepsy Panel

PLUSbpg-method Plus Analysis combines Sequence + Del/Dup (CNV) Analysis providing increased diagnostic yield in certain clinical conditions, where the underlying genetic defect may be detectable by either of the analysis methods. Results in 3–4 weeks. SEQbpg-method Our Sequence Analysis is based on a proprietary targeted sequencing method OS-Seq™ and offers panels targeted for genes associated with certain phenotypes. A standard way to analyze NGS data for finding the genetic cause for Mendelian disorders. Results in 3–4 weeks. DEL/DUPbpg-method Targeted Del/Dup (CNV) analysis is used to detect bigger disease causing deletions or duplications from the disease-associated genes. Results in 3–4 weeks.

Test code: NE1601

The Blueprint Genetics Metabolic Epilepsy Panel is a 30 gene test for genetic diagnostics of patients with clinical suspicion of inherited metabolic disorder causing epileptic seizures.

The mainstay of diagnosis of inborn errors of metabolism (IEMs) is biochemical investigation as metabolites may be assayed in blood, urine, or CSF. Genetic diagnosis constitutes the first line of investigation in those instances where there are no characteristic metabolites or diagnostic enzyme assay available. In several instances, it confirms the diagnosis suggested by biochemical analysis. Genetic testing is leading to expansion of the epileptic phenotypes of many of the genetic and indeed the metabolic epilepsies. It is important to recognize and diagnose this group of disorders, since they may be treatable, and there are significant implications for genetic counseling. This panel is part of the Comprehensive Epilepsy Panel.

About Metabolic Epilepsy

Epileptic seizures are a frequent symptom in metabolic disease, having been reported in more than 200 different inborn errors of metabolism (IEMs), and seizures are a relatively common reason for referral to the metabolic paediatrician or biochemical geneticist (PubMed: 22998469). As an example, GLUT1 deficiency syndrome is known to be a cause of drug-resistant childhood absence epilepsy and of adult-onset absence epilepsy with a normal CSF glucose. Molecular genetic analysis of the SLC2A1 gene is considered the standard criterion for diagnosis of GLUT1 deficiency syndrome. Epilepsy in GLUT1 deficiency is drug resistant and may be aggravated by fasting and by AEDs that inhibit GLUT1. GLUT1 deficiency is eminently treatable with the ketogenic diet, which should be commenced at the earliest opportunity and continued until at least adolescence.


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:

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Genes in the Metabolic Epilepsy Panel and their clinical significance
Gene Associated phenotypes Inheritance ClinVar HGMD
ADSL Adenylosuccinase deficiency AR 22 53
AGA Aspartylglucosaminuria AR 29 35
ALDH5A1 Succinic semialdehyde dehydrogenase deficiency AR 8 67
ALDH7A1 Epilepsy, pyridoxine-dependent AR 29 110
AMT Glycine encephalopathy AR 26 51
ARG1 Hyperargininemia AR 13 52
BTD Biotinidase deficiency AR 165 231
DPYD 5-fluorouracil toxicity AD/AR 10 96
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/AR 89 161
GAMT Guanidinoacetate methyltransferase deficiency AR 12 53
GCDH Glutaric aciduria AR 36 198
GCH1 Dopa-Responsive Dystonia Hyperphenylalaninemia, BH4-deficient, GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia AD/AR 25 229
GLDC Glycine encephalopathy AR 89 214
GNE Inclusion body myopathy, Nonaka myopathy, Sialuria AD/AR 32 193
GPHN Hyperekplexia, Molybdenum cofactor deficiency AD/AR 25 20
L2HGDH L-2-hydroxyglutaric aciduria AR 8 75
MOCS1 Molybdenum cofactor deficiency AR 7 32
MTHFR Homocystinuria due to MTHFR deficiency AR 51 127
PGK1 Phosphoglycerate kinase 1 deficiency XL 14 26
PNPO Pyridoxamine 5'-phosphate oxidase deficiency AR 14 28
PRODH* Hyperprolinemia AR 19 26
PTS Hyperphenylalaninemia, BH4-deficient AR 11 84
QDPR Hyperphenylalaninemia, BH4-deficient AR 8 55
SLC2A1 Stomatin-deficient cryohydrocytosis with neurologic defects, Epilepsy, idiopathic generalized, GLUT1 deficiency syndrome AD/AR 65 253
SLC25A15* Hyperornithinemia-hyperammonemia-homocitrullinemia syndrome AR 18 35
SLC46A1 Folate malabsorption AR 17 19
SUOX Sulfocysteinuria AR 6 26

*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 (; HGMD, refers to a number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD, The list of associated (gene specific) phenotypes are generated from CDG ( or Orphanet ( databases.

Blueprint Genetics offers a comprehensive Metabolic Epilepsy Panel that covers classical genes associated with 4-hydroxybutyric aciduria, 6-pyruvoyl-tetrahydropterin synthase deficiency, adenylosuccinate lyase deficiency, argininemia, aspartylglucosaminuria, biotinidase deficiency, dihydropteridine reductase deficiency, dihydropyrimidine dehydrogenase deficiency, GLUT1 deficiency syndrome, GTP cyclohydrolase I deficiency, glutaryl-CoA dehydrogenase deficiency, glycine encephalopathy, glycogen storage disease due to phosphoglycerate kinase 1 deficiency, guanidinoacetate methyltransferase deficiency, hereditary folate malabsorption, hereditary pheochromocytoma-paraganglioma, homocystinuria due to methylene tetrahydrofolate reductase deficiency, hyperornithinemia-hyperammonemia-homocitrullinuria, hyperprolinemia type 1, inherited metabolic disorder causing epileptic seizures, isolated sulfite oxidase deficiency, l-2-hydroxyglutaric aciduria, multiple acyl-CoA dehydrogenation deficiency, pyridoxal phosphate-responsive seizures, pyridoxine-dependent epilepsy, sialuria, sulfite oxidase deficiency due to molybdenum cofactor deficiency type A and sulfite oxidase deficiency due to molybdenum cofactor deficiency type C. 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.

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. Average sensitivity and specificity in Blueprint NGS Panels is 99.3% and 99.9% for detecting SNPs. Sensitivity to for indels vary depending on the size of the alteration: 1-10bps (96.0%), 11-20 bps (88.4%) and 21-30 bps (66.7%). The longest detected indel was 46 bps by sequence analysis. Detection limit for Del/Dup (CNV) analysis varies through the genome depending on exon size, sequencing coverage and sequence content. The sensitivity is 71.5% for single exon deletions and duplications and 99% for three exons’ deletions and duplications. We have validated the assays for different starting materials including EDTA-blood, isolated DNA (no FFPE) and saliva that all provide high-quality results. 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.

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 (, the NHLBI GO Exome Sequencing Project (ESP;, the Exome Aggregation Consortium (ExAC;, ClinVar database of genotype-phenotype associations ( and the Human Gene Mutation Database ( The consequence of variants in coding and splice regions are estimated using the following in silico variant prediction tools: SIFT (, Polyphen (, and Mutation Taster (

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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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.

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