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IllnessEpilepsies, metabolic; differentialdiagnosis

Summary

Short information

Comprehensive differential diagnostic panel for Epilepsies, metabolic comprising 8 or 82 curated genes (43 guideline-curated) according to the clinical signs

ID
EP0374
Number of genes
58 Accredited laboratory test
Examined sequence length
14,4 kb (Core-/Core-canditate-Genes)
87,4 kb (Extended panel: incl. additional genes)
Analysis Duration
on request
Material
  • EDTA-anticoagulated blood (3-5 ml)
Diagnostic indications

NGS +

[[Sanger]]

 

Gene panel

Selected genes

NameExon Length (bp)OMIM-GReferenz-Seq.Heredity
ALDH7A11620NM_001182.5AR
CLN31317NM_001042432.2AR
FOLR1774NM_016725.3AR
GAMT711NM_000156.6AR
GLDC3063NM_000170.3AR
POLG3720NM_002693.3AR, AD
SLC2A11479
  • No OMIM-Gs linked
NM_006516.4AD, AR
TPP11692NM_000391.4AR
ABAT1503NM_000663.5AR
AGK1269NM_018238.4AR
ALDH5A11608NM_001080.3AR
AMT1212NM_000481.4AR
ATP7A4503NM_000052.7XLR
BCKDK1098NM_001122957.4AR
BOLA3324NM_212552.3AR
CLN51077NM_006493.4AR
CLN6936NM_017882.3AR
CLN8861NM_018941.4AR
COQ8A1944NM_020247.5AR
CTSD1239NM_001909.5AR
CTSF1455NM_003793.4AR
DGUOK834NM_080916.3AR
DHFR564NM_000791.4AR
DNAJC5597NM_025219.3AD
FBXL41866NM_012160.5AR
FH1533NM_000143.4AR
GALC2058NM_000153.4AR
GATM1272NM_001482.3AR
GCSH522NM_004483.5AR
GLRX5474NM_016417.3AR
GPHN2310NM_020806.5AR, AD
GRN1782NM_002087.4AR
HCFC16108NM_005334.3XLR
HLCS2181NM_000411.8AR
IBA571071NM_001010867.4AR
KCTD7870NM_153033.5AR
L2HGDH1392NM_024884.3AR
LIAS990NM_001278590.2AR
MFSD81557NM_152778.3AR
MOCS11158NM_001075098.4AR
MOCS2567NM_004531.5AR
MPV17531NM_002437.5AR
NFU1765NM_001002755.4AR
OPA12883NM_015560.3AR, Mult
PNPO786NM_018129.4AR
PPT1921NM_000310.4AR
RRM2B1272NM_015713.5AR, AD
SLC25A4897NM_001151.4AR
SLC6A92121NM_201649.4AR
SLC8A12907NM_001112800.2AD
SUCLA21392NM_003850.3AR
SUCLG11041NM_003849.4AR
SUOX1638NM_000456.3AR
TANGO21252NM_152906.7AR
TBC1D241680NM_001199107.2AR
TFAM645NM_001270782.2AR
TWNK2055NM_021830.5AR
TYMP1449NM_001953.5AR

Informations about the disease

Clinical Comment

Neuro-metabolic epilepsies are inherited disorders with predominantly epileptic manifestations, or the epilepsy is part of a complex neurologic phenotype. Several of these disorders are treatable, but there are no specific clinical or electrographic features suggestive of metabolic epilepsies. Metabolic disorders can cause seizures in three different ways: Deficiency of substrates essential for neuro-cellular metabolism or membrane function, intracellular accumulation of neurotoxic substances, and alteration of intracellular osmolality in the brain. Thus, about half of the approximately 400 inborn errors of metabolism, i.e., manifold mutations in nearly 900 genes, may be associated with epilepsies. A search of the OMIM, PubMed and MEDLINE databases reveals that the majority of inborn errors of metabolism in epilepsy are transmitted in autosomal recessive manner (87%), whereas 6% are inherited in mitochondrial, 4% in X-linked and 3% in autosomal dominant manner. According to different study results, the DNA diagnostic yield can vary between 25-65% and more, so that nevertheless inconspicuous genetic findings do not mean a secure exclusion of the clinical suspected diagnoses.

References: https://www.ncbi.nlm.nih.gov/books/NBK1195/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369901/

 

Synonyms
  • Allelic: Anemia, sideroblastic, 3, pyridoxine-refractory (GLRX5)
  • Allelic: Aphasia, primary progressive (GRN)
  • Allelic: Behr syndrome (OPA1)
  • Allelic: Charcot-Marie-Tooth disease, axonal, type 2EE (MPV17)
  • Allelic: Deafness, AD 65 (TBC1D24)
  • Allelic: Deafness, AR 86 (TBC1D24)
  • Allelic: Dystonia 9 (SLC2A1)
  • Allelic: Fanconi renotubular syndrome 1 (GATM)
  • Allelic: Frontotemporal lobar degeneration with ubiquitin-positive inclusions (GRN)
  • Allelic: Glaucoma, normal tension, susceptibility to (OPA1)
  • Allelic: Leiomyomatosis + renal cell cancer (FH)
  • Allelic: Macular dystrophy with central cone involvement (MFSD8)
  • Allelic: Mitochondrial DNA depletion syndrome 2, myopathic type (TK2)
  • Allelic: Optic atrophy 1 (OPA1)
  • Allelic: Optic atrophy plus syndrome (OPA1)
  • Allelic: Perrault syndrome 5 (TWNK)
  • Allelic: Portal hypertension, noncirrhotic, 1 (DGUOK)
  • Allelic: Progressive external ophthalmoplegia with mitochondrial DNA deletions, AR 4 (DGUOK)
  • Allelic: Progressive external ophthalmoplegia, AD 1 (POLG)
  • Allelic: Progressive external ophthalmoplegia, AR 1 (POLG)
  • Allelic: Spastic paraplegia 74, AR (IBA57)
  • Branched-chain ketoacid dehydrogenase kinase deficiency (BCKDK)
  • Cerebral creatine deficiency syndrome 2 (GAMT)
  • Cerebral creatine deficiency syndrome 3 (GATM)
  • Ceroid lipofuscinosis, neuronal, 1 (PPT1)
  • Ceroid lipofuscinosis, neuronal, 10 (CTSD)
  • Ceroid lipofuscinosis, neuronal, 11 (GRN)
  • Ceroid lipofuscinosis, neuronal, 13, Kufs type, AD (CTSF)
  • Ceroid lipofuscinosis, neuronal, 2 (TPP1)
  • Ceroid lipofuscinosis, neuronal, 3 (CLN3)
  • Ceroid lipofuscinosis, neuronal, 4, Kufs type (DNAJC5)
  • Ceroid lipofuscinosis, neuronal, 5 (CLN5)
  • Ceroid lipofuscinosis, neuronal, 6A (CLN6)
  • Ceroid lipofuscinosis, neuronal, 6B, Kufs type (CLN6)
  • Ceroid lipofuscinosis, neuronal, 7 (MFSD8)
  • Ceroid lipofuscinosis, neuronal, 8 (CLN8)
  • Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant (CLN8)
  • Coenzyme Q10 deficiency, primary, 4 (COQ8A)
  • Constitutional megaloblastic anemia with severe neurologic disease (DHFR)
  • DOORS [Deafness, Onychodystrophy, Osteodystrophy, mental Retard.] syndrome (TBC1D24)
  • Developmental + epileptic encephalopathy 16 (TBC1D24)
  • Epilepsy, idiopathic generalized, susceptibility to, 12 (SLC2A1)
  • Epilepsy, progressive myoclonic 3, with/-out intracellular inclusions (KCTD7)
  • Epilepsy, pyridoxine-dependent (ALDH7A1)
  • Epilepsy, rolandic, with proxysmal exercise-induce dystonia + writer's cramp (TBC1D24)
  • Epilepsy-associated gene [Lit.] (SLC8A9)
  • Fumarase deficiency (FH)
  • GABA-transaminase deficiency (ABAT)
  • GLUT1 deficiency syndrome 1, infantile onset, severe (SLC2A1)
  • GLUT1 deficiency syndrome 2, childhood onset (SLC2A1)
  • Glycine encephalopathy (GCSH)
  • Glycine encephalopathy (GLDC)
  • Glycine encephalopathy with normal serum glycine (SLC6A9)
  • Hyperglycinemia, lactic acidosis + seizures (LIAS)
  • Krabbe disease (GALC)
  • L-2-hydroxyglutaric aciduria (L2HGDH)
  • Megaloblastic anemia with severe neurologic disease (DHFR)
  • Metabolic encephalomyopathic crises, recurrent, rhabdomyol., cardiac arrhythmias, neurodeg. (TANGO2)
  • Metabolic encephalomyopathic crises, recurrent, rhabdomyolysis, cardiac arrhyth., neurodeg. (TANGO2)
  • Methylmalonic acidemia + homocysteinemia, cblX type (HCFC1)
  • Mitochondrial DNA depletion syndrome 1, MNGIE type (TYMP)
  • Mitochondrial DNA depletion syndrome 12A, cardiomyopathic type, AD (SLC25A4
  • Mitochondrial DNA depletion syndrome 12B, cardiomyopathic type, AR (SLC25A4)
  • Mitochondrial DNA depletion syndrome 13, encephalomyopathic type (FBXL4)
  • Mitochondrial DNA depletion syndrome 14, encephalocardiomyopathic type (OPA1)
  • Mitochondrial DNA depletion syndrome 15, hepatocerebral type (TFAM)
  • Mitochondrial DNA depletion syndrome 3, hepatocerebral type (DGUOK)
  • Mitochondrial DNA depletion syndrome 4A, Alpers type (POLG)
  • Mitochondrial DNA depletion syndrome 4B, MNGIE type (POLG)
  • Mitochondrial DNA depletion syndrome 5, encephalomyopathic +/- methylmalonic aciduria (SULC2)
  • Mitochondrial DNA depletion syndrome 6, hepatocerebral type (MPV17)
  • Mitochondrial DNA depletion syndrome 7, hepatocerebral type (TWNK)
  • Mitochondrial DNA depletion syndrome 8A, encephalomyopathic type with renal tubulopathy (RRM2B)
  • Mitochondrial DNA depletion syndrome 8B, MNGIE type (RRM2B)
  • Mitochondrial DNA depletion syndrome 9, encephalomyopathic type with methylmalonic aciduria (SUCLG1)
  • Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE] (POLG)
  • Molybdenum cofactor deficiency A (MOCS1)
  • Molybdenum cofactor deficiency B (MOCS2)
  • Molybdenum cofactor deficiency C (GPHN)
  • Multiple mitochondrial dysfunctions syndrome 1 (NFU1)
  • Multiple mitochondrial dysfunctions syndrome 2 with hyperglycinemia (BOLA3)
  • Multiple mitochondrial dysfunctions syndrome 3 (IBA57)
  • Myoclonic epilepsy, infantile, familial (TBC1D24)
  • Neurodegeneration due to cerebral folate transport deficiency (FOLR1)
  • Progressive external ophthalmoplegia with mitochondrial DNA deletions, AD 2 (SLC25A4)
  • Progressive external ophthalmoplegia with mitochondrial DNA deletions, AD 3 (TWNK)
  • Progressive external ophthalmoplegia with mitochondrial DNA deletions, AD 5 (RRM2B)
  • Progressive external ophthalmoplegia with mitochondrial DNA deletions, AR 2 (RNASEH1)
  • Progressive external ophthalmoplegia with mitochondrial DNA deletions, AR 3 (TK2)
  • Pyridoxamine 5'-phosphate oxidase deficiency (PNPO)
  • Sengers syndrome (AGK)
  • Spasticity, childhood-onset, with hyperglycinemia (GLRX5)
  • Spinocerebellar ataxia, autosomal recessive 7 (TPP1)
  • Stomatin-deficient cryohydrocytosis with neurologic defects (SLC2A1)
  • Succinic semialdehyde dehydrogenase deficiency (ALDH5A1)
  • Sulfite oxidase deficiency (SUOX)
Heredity, heredity patterns etc.
  • AD
  • AR
  • Mult
  • XLR
OMIM-Ps
  • Multiple OMIM-Ps
ICD10 Code

Bioinformatics and clinical interpretation

Test-Stärken

  • DAkkS-akkreditiertes Labor
  • EU-Richtlinie für IVD in Umsetzung
  • Qualitäts-kontrolliert arbeitendes Personal
  • Leistungsstarke Sequenzierungstechnologien, fortschrittliche Target-Anreicherungsmethoden und Präzisions-Bioinformatik-Pipelines sorgen für überragende analytische Leistung
  • Sorgfältige Kuratierung klinisch relevanter und wissenschaftlich begründeter Gen-Panels
  • eine Vielzahl nicht Protein-kodierender Varianten, die in unseren klinischen NGS-Tests mit erfasst werden
  • unser strenges Variantenklassifizierungsschema nach ACMG-Kriterien
  • unser systematischer klinischer Interpretations-Workflow mit proprietärer Software ermöglicht die genaue und nachvollziehbare Verarbeitung von NGS-Daten
  • unsere umfassenden klinischen Aussagen

Testeinschränkungen

  • Gene mit eingeschränkter Abdeckung werden gekennzeichnet
  • Gene mit kompletten oder partiellen Duplikationen werden gekennzeichnet
  • es wird angenommen, dass ein Gen suboptimal abgedeckt ist, wenn >90% der Nukleotide des Gens bei einem Mapping-Qualitätsfaktor von >20 (MQ>20) nicht abgedeckt sind
  • die Sensitivität der Diagnostik zur Erkennung von Varianten mit genannten Testeinschränkungen ist möglicherweise begrenzt bei:
  • Gen-Konversionen
  • komplexe Inversionen
  • Balancierte Translokationen
  • Mitochondriale Varianten
  • Repeat-Expansionen, sofern nicht anders dokumentiert
  • nicht kodierende Varianten, die Krankheiten verursachen, die von diesem Panel nicht mit abgedeckt werden
  • niedriger Mosaik-Status
  • Repeat-Blöcke von Mononukleotiden
  • Indels >50bp (Insertionen-Deletionen)
  • Deletionen oder Duplikationen einzelner Exons
  • Varianten innerhalb von Pseudogenen
  • die analytische Sensitivität kann geringer ausfallen werden, wenn die DNA nicht von amedes genetics extrahiert wurde

Laboratory requirement

  • Die in grün gezeigten Gene sind kuratiert und werden als Gen-Panel untersucht. Eine Erweiterung des Panels (blau gezeigte Gene, jeweils ebenfalls kuratiert) kann auf Anfrage erfolgen. Sofern unter "Erweitertes Panel" ein Minuszeichen angezeigt wird, sind nur Core-/Basis-Gene verfügbar.

  • Für die Anforderung einer genetischen Untersuchung senden Sie uns bitte die Krankheits-ID auf einem Überweisungsschein. Bitte die Material-Angabe beachten.

  • Für privat versicherte Patienten empfehlen wir einen Antrag auf Kostenübernahme bei der Krankenversicherung.

  • Die Untersuchung wird auch für Selbstzahler angeboten.