PEBEL2
MCID: ENC066
MIFTS: 25

Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or Leukoencephalopathy, 2 (PEBEL2)

Categories: Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or...

MalaCards integrated aliases for Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or Leukoencephalopathy, 2:

Name: Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or Leukoencephalopathy, 2 57 72 29 6
Pebel2 57 72
Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or Leukoencephalopathy, Type 2 39
Nad Hx Dehydratase Deficiency 58
Carkd Deficiency 58

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy or early childhood
death in early childhood
episodic regression associated with illness, fever, stress


HPO:

31
encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 2:
Onset and clinical course death in infancy
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or...

OMIM® : 57 Early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy-2 (PEBEL2) is an autosomal recessive severe neurometabolic disorder characterized by rapidly progressive neurologic deterioration that is usually associated with a febrile illness. Affected infants tend to show normal early development followed by acute psychomotor regression with ataxia, hypotonia, and sometimes seizures, resulting in death in the first years of life. Brain imaging shows multiple abnormalities, including brain edema and signal abnormalities in the cortical and subcortical regions (summary by Van Bergen et al., 2019). For a discussion of genetic heterogeneity of PEBEL, see PEBEL1 (617186). (618321) (Updated 20-May-2021)

MalaCards based summary : Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or Leukoencephalopathy, 2, is also known as pebel2. An important gene associated with Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or Leukoencephalopathy, 2 is NAXD (NAD(P)HX Dehydratase). Affiliated tissues include brain, bone marrow and bone, and related phenotypes are hearing impairment and ophthalmoplegia

UniProtKB/Swiss-Prot : 72 Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 2: An autosomal recessive severe neurometabolic disorder characterized by severe leukoencephalopathy usually associated with a trivial febrile illness. Affected infants tend to show normal early development followed by acute psychomotor regression with ataxia, hypotonia, respiratory insufficiency, and seizures. Disease course is rapidly progressive, leading to coma, global brain atrophy, and death in the first years of life. Brain imaging shows multiple abnormalities, including brain edema and signal abnormalities in the cortical and subcortical regions.

Related Diseases for Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or...

Diseases in the Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or Leukoencephalopathy, 1 family:

Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or Leukoencephalopathy, 2

Symptoms & Phenotypes for Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or...

Human phenotypes related to Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or Leukoencephalopathy, 2:

31 (show all 21)
# Description HPO Frequency HPO Source Accession
1 hearing impairment 31 very rare (1%) HP:0000365
2 ophthalmoplegia 31 very rare (1%) HP:0000602
3 cardiomyopathy 31 very rare (1%) HP:0001638
4 pancytopenia 31 very rare (1%) HP:0001876
5 seizure 31 very rare (1%) HP:0001250
6 ataxia 31 HP:0001251
7 chorea 31 HP:0002072
8 developmental regression 31 HP:0002376
9 vomiting 31 HP:0002013
10 irritability 31 HP:0000737
11 dystonia 31 HP:0001332
12 skin rash 31 HP:0000988
13 lethargy 31 HP:0001254
14 encephalopathy 31 HP:0001298
15 cerebral atrophy 31 HP:0002059
16 diarrhea 31 HP:0002014
17 abnormality of the cerebral white matter 31 HP:0002500
18 loss of speech 31 HP:0002371
19 cerebral edema 31 HP:0002181
20 gliosis 31 HP:0002171
21 neurodegeneration 31 HP:0002180

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
ataxia
chorea
developmental regression
irritability
dystonia
more
Skin Nails Hair Skin:
skin rash
skin lesions
epidermolysis
affects groin and axillae

Head And Neck Ears:
hearing loss (in some patients)

Hematology:
pancytopenia (in some patients)
hypocellular bone marrow (in some patients)

Laboratory Abnormalities:
patient cells may show abnormalities in mitochondrial respiration

Abdomen Gastrointestinal:
vomiting
diarrhea

Head And Neck Eyes:
ophthalmoplegia (in some patients)

Cardiovascular Heart:
cardiomyopathy (in some patients)

Metabolic Features:
metabolic decompensation

Clinical features from OMIM®:

618321 (Updated 20-May-2021)

Drugs & Therapeutics for Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or...

Search Clinical Trials , NIH Clinical Center for Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or Leukoencephalopathy, 2

Genetic Tests for Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or...

Genetic tests related to Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or Leukoencephalopathy, 2:

# Genetic test Affiliating Genes
1 Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or Leukoencephalopathy, 2 29 NAXD

Anatomical Context for Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or...

MalaCards organs/tissues related to Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or Leukoencephalopathy, 2:

40
Brain, Bone Marrow, Bone

Publications for Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or...

Articles related to Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or Leukoencephalopathy, 2:

# Title Authors PMID Year
1
NAD(P)HX dehydratase protein-truncating mutations are associated with neurodevelopmental disorder exacerbated by acute illness. 57 6
32462209 2020
2
NAD(P)HX dehydratase (NAXD) deficiency: a novel neurodegenerative disorder exacerbated by febrile illnesses. 6 57
30576410 2019
3
Reply: NAD(P)HX dehydratase protein-truncating mutations are associated with neurodevelopmental disorder exacerbated by acute illness. 57
32462208 2020

Variations for Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or...

ClinVar genetic disease variations for Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or Leukoencephalopathy, 2:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 NAXD NM_001242882.1(NAXD):c.839+1G>T SNV Pathogenic 617756 rs1566623786 GRCh37: 13:111289597-111289597
GRCh38: 13:110637250-110637250
2 NAXD NM_001242882.1(NAXD):c.948_949insTT (p.Ala317fs) Insertion Pathogenic 617757 rs778824382 GRCh37: 13:111290833-111290834
GRCh38: 13:110638486-110638487
3 NAXD NM_001242883.1(NAXD):c.57-5083G>A SNV Pathogenic 617758 rs1566614549 GRCh37: 13:111274703-111274703
GRCh38: 13:110622356-110622356
4 NAXD NM_001242883.1(NAXD):c.57-5216_57-5213del Deletion Pathogenic 617759 rs773887880 GRCh37: 13:111274567-111274570
GRCh38: 13:110622220-110622223
5 NAXD NM_018210.4(NAXD):c.-30del Deletion Pathogenic 978059 GRCh37: 13:111267992-111267992
GRCh38: 13:110615645-110615645
6 NAXD NM_001242882.1(NAXD):c.922C>T (p.Arg308Cys) SNV Likely pathogenic 617755 rs767778853 GRCh37: 13:111290807-111290807
GRCh38: 13:110638460-110638460
7 NAXD NM_001242882.2(NAXD):c.181G>C (p.Val61Leu) SNV Uncertain significance 1031245 GRCh37: 13:111274697-111274697
GRCh38: 13:110622350-110622350
8 NAXD NM_001242882.2(NAXD):c.923G>A (p.Arg308His) SNV Uncertain significance 1031246 GRCh37: 13:111290808-111290808
GRCh38: 13:110638461-110638461
9 NAXD NM_001242882.2(NAXD):c.46G>A (p.Val16Ile) SNV Uncertain significance 1031247 GRCh37: 13:111267994-111267994
GRCh38: 13:110615647-110615647

UniProtKB/Swiss-Prot genetic disease variations for Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or Leukoencephalopathy, 2:

72
# Symbol AA change Variation ID SNP ID
1 NAXD p.Gly81Ser VAR_082224
2 NAXD p.Arg326Cys VAR_082225

Expression for Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or...

Search GEO for disease gene expression data for Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or Leukoencephalopathy, 2.

Pathways for Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or...

GO Terms for Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or...

Sources for Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or...

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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