PEBEL1
MCID: ENC069
MIFTS: 24

Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or Leukoencephalopathy, 1 (PEBEL1)

Categories: Genetic diseases, Neuronal 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, 1:

Name: Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or Leukoencephalopathy, 1 57
Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or Leukoencephalopathy 57 74 29 6 17
Pebel 57 74 37
Pebel1 57

Characteristics:

OMIM:

57
Miscellaneous:
rapidly progressive
death in early childhood
onset usually associated with febrile illness
onset in first years of life after normal development
undulating course (in some patients)

Inheritance:
autosomal recessive


HPO:

32
encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1:
Clinical modifier death in infancy
Inheritance autosomal recessive inheritance
Onset and clinical course rapidly progressive


Classifications:



External Ids:

KEGG 37 H02262
MeSH 44 D020271

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

OMIM : 57 Early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy-1 (PEBEL1) 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, respiratory insufficiency, and seizures, resulting in coma 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 (summary by Kremer et al., 2016). (617186)

MalaCards based summary : Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or Leukoencephalopathy, 1, also known as encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, is related to encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 2. An important gene associated with Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or Leukoencephalopathy, 1 is NAXE (NAD(P)HX Epimerase). Affiliated tissues include brain and skin, and related phenotypes are brain atrophy and nystagmus

KEGG : 37
Early-onset progressive encephalopathy with brain edema and leukoencephalopathy (PEBEL) is an autosomal recessive infancy-onset disease characterized by ataxia, cerebellar edema, spinal myelopathy, and skin lesions. It is induced by febrile infections, leading to coma and finally to death within the first 3 years of life. NAXE mutations disrupt the cellular NAD(P)HX repair system and cause PEBEL.

UniProtKB/Swiss-Prot : 74 Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy: 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

Diseases related to Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or Leukoencephalopathy, 1 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 2 11.3

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, 1:

32 (show all 19)
# Description HPO Frequency HPO Source Accession
1 brain atrophy 32 HP:0012444
2 nystagmus 32 HP:0000639
3 seizures 32 HP:0001250
4 ataxia 32 HP:0001251
5 tremor 32 HP:0001337
6 developmental regression 32 HP:0002376
7 generalized hypotonia 32 HP:0001290
8 strabismus 32 HP:0000486
9 increased serum lactate 32 HP:0002151
10 lactic acidosis 32 HP:0003128
11 coma 32 HP:0001259
12 cerebral edema 32 HP:0002181
13 encephalopathy 32 HP:0001298
14 leukoencephalopathy 32 HP:0002352
15 increased csf lactate 32 HP:0002490
16 skin erosion 32 HP:0200041
17 tetraparesis 32 HP:0002273
18 cerebellar edema 32 HP:0030915
19 myelopathy 32 HP:0002196

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
brain atrophy
seizures
ataxia
tremor
coma
more
Laboratory Abnormalities:
increased serum lactate
increased csf lactate

Skin Nails Hair Skin:
skin erosion
skin blistering
erythematous bullous skin lesions

Respiratory:
respiratory failure due to hypotonia

Head And Neck Eyes:
nystagmus
strabismus

Metabolic Features:
lactic acidosis

Muscle Soft Tissue:
hypotonia
mitochondrial dysfunction seen on muscle biopsy (in some patients)

Clinical features from OMIM:

617186

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, 1

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, 1:

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

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, 1:

41
Brain, Skin

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

Articles related to Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or Leukoencephalopathy, 1:

# Title Authors PMID Year
1
NAXE Mutations Disrupt the Cellular NAD(P)HX Repair System and Cause a Lethal Neurometabolic Disorder of Early Childhood. 8 71
27616477 2016
2
Homozygous mutation in the APOA1BP is associated with a lethal infantile leukoencephalopathy. 8
27122014 2016
3
New perspective in diagnostics of mitochondrial disorders: two years' experience with whole-exome sequencing at a national paediatric centre. 71
27290639 2016

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, 1:

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 NAXE NM_144772.3(NAXE): c.177C> A (p.Tyr59Ter) single nucleotide variant Pathogenic rs371872027 1:156561773-156561773 1:156591981-156591981
2 NAXE NM_144772.3(NAXE): c.196C> T (p.Gln66Ter) single nucleotide variant Pathogenic rs759251812 1:156561906-156561906 1:156592114-156592114
3 NAXE NM_144772.3(NAXE): c.516+1G> A single nucleotide variant Pathogenic rs139093330 1:156562463-156562463 1:156592671-156592671
4 NAXE NM_144772.3(NAXE): c.804_807delinsA (p.Lys270del) indel Pathogenic rs886041062 1:156563813-156563816 1:156594021-156594024
5 NAXE NM_144772.3(NAXE): c.743del (p.Ala248fs) deletion Pathogenic rs886041063 1:156563752-156563752 1:156593960-156593960
6 NAXE NM_144772.3(NAXE): c.653A> T (p.Asp218Val) single nucleotide variant Pathogenic rs886041064 1:156563336-156563336 1:156593544-156593544
7 NAXE NM_144772.3(NAXE): c.326dup (p.Thr110fs) duplication Uncertain significance 1:156562191-156562191 1:156592399-156592399

UniProtKB/Swiss-Prot genetic disease variations for Encephalopathy, Progressive, Early-Onset, with Brain Edema and/or Leukoencephalopathy, 1:

74
# Symbol AA change Variation ID SNP ID
1 NAXE p.Ala94Asp VAR_077991 rs879255647
2 NAXE p.Asp218Val VAR_077992 rs886041064

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, 1.

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
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
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36 IUPHAR
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46 MGI
49 NCI
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51 NDF-RT
54 NINDS
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57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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