New-onset refractory status epilepticus

Summary

New-onset refractory status epilepticus (MONDO:0018199) is a disease with 1 cohort gene and 1 clinical trial. Top therapeutic interventions include anakinra.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 37
• Clinical trials: 1

Clinical features

Signs & symptoms

Clinical features (HPO)

37 HPO clinical features (Orphanet curated; top 37 by frequency):

HPO ID	Term	Frequency
HP:0002133	Status epilepticus	Obligate (100%)
HP:0025373	Interictal EEG abnormality	Very frequent (80-99%)
HP:0032867	Refractory status epilepticus	Very frequent (80-99%)
HP:0032894	Seizure precipitated by febrile infection	Very frequent (80-99%)
HP:0001945	Fever	Frequent (30-79%)
HP:0002384	Focal impaired awareness seizure	Frequent (30-79%)
HP:0002457	Abnormal head movements	Frequent (30-79%)
HP:0002922	Increased CSF protein concentration	Frequent (30-79%)
HP:0002960	Autoimmunity	Frequent (30-79%)
HP:0004302	Functional motor deficit	Frequent (30-79%)
HP:0007183	Focal T2 hyperintense basal ganglia lesion	Frequent (30-79%)
HP:0007334	Bilateral tonic-clonic seizure with focal onset	Frequent (30-79%)
HP:0010845	EEG with generalized slow activity	Frequent (30-79%)
HP:0011117	Abnormal circulating interleukin concentration	Frequent (30-79%)
HP:0011154	Focal autonomic seizure	Frequent (30-79%)
HP:0011468	Facial tics	Frequent (30-79%)
HP:0012229	CSF pleocytosis	Frequent (30-79%)
HP:0020217	Focal aware motor seizure	Frequent (30-79%)
HP:0033716	EEG with frontal epileptiform discharges	Frequent (30-79%)
HP:0033717	EEG with temporal epileptiform discharges	Frequent (30-79%)
HP:0100543	Cognitive impairment	Frequent (30-79%)
HP:0410263	Brain imaging abnormality	Frequent (30-79%)
HP:0000708	Atypical behavior	Occasional (5-29%)
HP:0001289	Confusion	Occasional (5-29%)
HP:0002283	Global brain atrophy	Occasional (5-29%)
HP:0002315	Headache	Occasional (5-29%)
HP:0002383	Infectious encephalitis	Occasional (5-29%)
HP:0010841	Multifocal epileptiform discharges	Occasional (5-29%)
HP:0010850	EEG with spike-wave complexes	Occasional (5-29%)
HP:0011198	EEG with generalized epileptiform discharges	Occasional (5-29%)
HP:0012378	Fatigue	Occasional (5-29%)
HP:0012696	Abnormal thalamic MRI signal intensity	Occasional (5-29%)
HP:0030915	Cerebellar edema	Occasional (5-29%)
HP:0031358	Vegetative state	Occasional (5-29%)
HP:0032794	Myoclonic seizure	Occasional (5-29%)
HP:0012751	Abnormal basal ganglia MRI signal intensity	Very rare (<1-4%)
HP:0031475	Status epilepticus without prominent motor symptoms	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	new-onset refractory status epilepticus
Mondo ID	MONDO:0018199
Orphanet	363558
UMLS	C4749462
MedGen	1657271
GARD	0012244
Is cancer (heuristic)	no

Also known as: De novo cryptogenic refractory multifocal febrile status epilepticus · New onset refractory status epilepticus · NORSE · Norse

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › epilepsy › epilepsy syndrome › childhood-onset epilepsy syndrome › new-onset refractory status epilepticus

Related subtypes (15): self-limited childhood occipital epilepsy, Landau-Kleffner syndrome, rolandic epilepsy-paroxysmal exercise-induced dystonia-writer’s cramp syndrome, perioral myoclonia with absences, cryptogenic late-onset epileptic spasms, rolandic epilepsy-speech dyspraxia syndrome, early-onset epileptic encephalopathy and intellectual disability due to GRIN2A mutation, familial partial epilepsy, acute encephalopathy with biphasic seizures and late reduced diffusion, atypical childhood epilepsy with centrotemporal spikes, Sunflower syndrome, childhood-onset genetic generalized epilepsy syndrome, childhood-onset idiopathic generalized epilepsy syndrome, childhood-onset epilepsy syndrome with developmental and/or epileptic encephalopathy, childhood-onset self-limited focal epilepsy syndrome

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3359048	NC_012920.1(MT-TW):m.5513G>A	MT-TW	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MT-TW	Orphanet:255210	Mitochondrial DNA-associated Leigh syndrome
MT-TW	Orphanet:550	MELAS

Cohort genes → proteins

1 cohort genes, 0 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MT-TW	HGNC:7501	ENSG00000210117		mitochondrially encoded tRNA-Trp (UGA/G)	clinvar

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MT-TW	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
leukocyte	1
monocyte	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MT-TW	114	ubiquitous	yes	sural nerve, monocyte, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MT-TW	0

Structural data

PDB: 0 · AlphaFold-only: 0 · No structure: 1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MT-TW	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	MT-TW

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
MT-TW	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07281027	PHASE3	NOT_YET_RECRUITING	COMparison Between Anakinra and Tocilizumab in NORSE - COMBAT-NORSE

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ANAKINRA	4	1
CHEMBL5220618	0	1