EIEE50
MCID: EPL183
MIFTS: 35

Epileptic Encephalopathy, Early Infantile, 50 (EIEE50)

Categories: Bone diseases, Ear diseases, Eye diseases, Fetal diseases, Genetic diseases, Liver diseases, Mental diseases, Metabolic diseases, Nephrological diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Epileptic Encephalopathy, Early Infantile, 50

MalaCards integrated aliases for Epileptic Encephalopathy, Early Infantile, 50:

Name: Epileptic Encephalopathy, Early Infantile, 50 56 73 29 6
Carbohydrate Deficient Glycoprotein Syndrome Type Iz 12 52 58
Congenital Disorder of Glycosylation Type 1z 12 52 58
Cdg Syndrome Type Iz 12 52 58
Cdg-Iz 12 52 58
Cdg1z 52 58 73
Early Infantile Epileptic Encephalopathy 50 12 15
Cad-Cdg 52 58
Eiee50 56 73
Congenital Disorder of Glycosylation, Type Iz, Formerly; Cdg1z, Formerly 56
Congenital Disorder of Glycosylation, Type Iz, Formerly 56
Encephalopathy, Epileptic, Early Infantile,, Type 50 39
Congenital Disorder of Glycosylation Type Iz 52
Early Infantile Epileptic Encephalopathy-50 52
Congenital Disorder of Glycosylation 1z 73
Cdg1z, Formerly 56

Characteristics:

Orphanet epidemiological data:

58
cad-cdg
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
death in early childhood may occur
onset in infancy (up to 2 years)
favorable response to treatment with oral uridine


HPO:

31
epileptic encephalopathy, early infantile, 50:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset progressive


Classifications:

Orphanet: 58  
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:0080419
OMIM 56 616457
OMIM Phenotypic Series 56 PS308350
ICD10 via Orphanet 33 E77.8
Orphanet 58 ORPHA448010

Summaries for Epileptic Encephalopathy, Early Infantile, 50

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 448010 Definition CAD-CDG is a rare congenital disorder of glycosylation caused by mutations in the CAD gene and characterized by epileptic encephalopathy , global developmental delay , normocytic anemia and anisopoikilocytosis. Loss of acquired skills in early childhood is present and natural disease course can be lethal in early childhood. Visit the Orphanet disease page for more resources.

MalaCards based summary : Epileptic Encephalopathy, Early Infantile, 50, also known as carbohydrate deficient glycoprotein syndrome type iz, is related to hemolytic anemia and congenital dyserythropoietic anemia. An important gene associated with Epileptic Encephalopathy, Early Infantile, 50 is CAD (Carbamoyl-Phosphate Synthetase 2, Aspartate Transcarbamylase, And Dihydroorotase). Affiliated tissues include brain, bone marrow and bone, and related phenotypes are global developmental delay and developmental regression

Disease Ontology : 12 An early infantile epileptic encephalopathy characterized by delayed psychomotor development, early-onset seizures, severe developmental regression, and normocytic anemia that has material basis in homozygous or compound heterozygous mutation in the CAD gene on chromosome 2p23.

OMIM : 56 Early infantile epileptic encephalopathy-50 is an autosomal recessive progressive neurodegenerative neurometabolic disorder characterized by delayed psychomotor development, early-onset seizures, severe developmental regression, and normocytic anemia. Onset is within the first years of life. Evidence suggests that affected children can have a favorable response to treatment with uridine (summary by Koch et al., 2017). For a discussion of genetic heterogeneity of early infantile epileptic encephalopathy, see 308350. (616457)

UniProtKB/Swiss-Prot : 73 Epileptic encephalopathy, early infantile, 50: A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. EIEE50 is an autosomal recessive, progressive disease with onset in infancy and favorable response to treatment with oral uridine.

Related Diseases for Epileptic Encephalopathy, Early Infantile, 50

Diseases in the Early Infantile Epileptic Encephalopathy family:

Epileptic Encephalopathy, Early Infantile, 9 Epileptic Encephalopathy, Early Infantile, 8
Epileptic Encephalopathy, Early Infantile, 2 Epileptic Encephalopathy, Early Infantile, 36
Epileptic Encephalopathy, Early Infantile, 1 Epileptic Encephalopathy, Early Infantile, 6
Epileptic Encephalopathy, Early Infantile, 3 Epileptic Encephalopathy, Early Infantile, 4
Epileptic Encephalopathy, Early Infantile, 39 Epileptic Encephalopathy, Early Infantile, 5
Epileptic Encephalopathy, Early Infantile, 7 Epileptic Encephalopathy, Early Infantile, 11
Epileptic Encephalopathy, Early Infantile, 12 Epileptic Encephalopathy, Early Infantile, 13
Epileptic Encephalopathy, Early Infantile, 14 Epileptic Encephalopathy, Early Infantile, 15
Epileptic Encephalopathy, Early Infantile, 16 Epileptic Encephalopathy, Early Infantile, 17
Epileptic Encephalopathy, Early Infantile, 18 Epileptic Encephalopathy, Early Infantile, 19
Epileptic Encephalopathy, Early Infantile, 21 Epileptic Encephalopathy, Early Infantile, 23
Epileptic Encephalopathy, Early Infantile, 24 Epileptic Encephalopathy, Early Infantile, 26
Epileptic Encephalopathy, Early Infantile, 27 Epileptic Encephalopathy, Early Infantile, 28
Epileptic Encephalopathy, Early Infantile, 29 Epileptic Encephalopathy, Early Infantile, 30
Epileptic Encephalopathy, Early Infantile, 31 Epileptic Encephalopathy, Early Infantile, 32
Epileptic Encephalopathy, Early Infantile, 33 Epileptic Encephalopathy, Early Infantile, 50
Epileptic Encephalopathy, Early Infantile, 34 Epileptic Encephalopathy, Early Infantile, 35
Epileptic Encephalopathy, Early Infantile, 37 Epileptic Encephalopathy, Early Infantile, 38
Epileptic Encephalopathy, Early Infantile, 40 Epileptic Encephalopathy, Early Infantile, 41
Epileptic Encephalopathy, Early Infantile, 42 Epileptic Encephalopathy, Early Infantile, 43
Epileptic Encephalopathy, Early Infantile, 44 Epileptic Encephalopathy, Early Infantile, 45
Epileptic Encephalopathy, Early Infantile, 46 Epileptic Encephalopathy, Early Infantile, 47
Epileptic Encephalopathy, Early Infantile, 48 Epileptic Encephalopathy, Early Infantile, 49
Epileptic Encephalopathy, Early Infantile, 51 Epileptic Encephalopathy, Early Infantile, 52
Epileptic Encephalopathy, Early Infantile, 53 Epileptic Encephalopathy, Early Infantile, 54
Epileptic Encephalopathy, Early Infantile, 55 Epileptic Encephalopathy, Early Infantile, 56
Epileptic Encephalopathy, Early Infantile, 57 Epileptic Encephalopathy, Early Infantile, 58
Epileptic Encephalopathy, Early Infantile, 59 Epileptic Encephalopathy, Early Infantile, 60
Epileptic Encephalopathy, Early Infantile, 61 Epileptic Encephalopathy, Early Infantile, 62
Epileptic Encephalopathy, Early Infantile, 63 Epileptic Encephalopathy, Early Infantile, 64
Epileptic Encephalopathy, Early Infantile, 65 Epileptic Encephalopathy, Early Infantile, 66
Epileptic Encephalopathy, Early Infantile, 67 Epileptic Encephalopathy, Early Infantile, 68
Epileptic Encephalopathy, Early Infantile, 69 Epileptic Encephalopathy, Early Infantile, 70
Epileptic Encephalopathy, Early Infantile, 71 Epileptic Encephalopathy, Early Infantile, 72
Epileptic Encephalopathy, Early Infantile, 73 Epileptic Encephalopathy, Early Infantile, 74
Epileptic Encephalopathy, Early Infantile, 75 Epileptic Encephalopathy, Early Infantile, 76
Epileptic Encephalopathy, Early Infantile, 77 Epileptic Encephalopathy, Early Infantile, 78
Epileptic Encephalopathy, Early Infantile, 79 Epileptic Encephalopathy, Early Infantile, 80
Epileptic Encephalopathy, Early Infantile, 81 Epileptic Encephalopathy, Early Infantile, 82
Epileptic Encephalopathy, Early Infantile, 83 Epileptic Encephalopathy, Early Infantile, 84
Epileptic Encephalopathy, Early Infantile, 86 Arx-Related Epileptic Encephalopathy

Diseases related to Epileptic Encephalopathy, Early Infantile, 50 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 hemolytic anemia 9.6 PKLR PIEZO1
2 congenital dyserythropoietic anemia 9.5 SEC23B PKLR
3 congenital nonspherocytic hemolytic anemia 9.5 PKLR PIEZO1
4 pyruvate kinase deficiency of red cells 9.5 PKLR PIEZO1
5 hemochromatosis, type 1 9.2 PKLR PIEZO1
6 congenital hemolytic anemia 9.1 SEC23B PKLR PIEZO1
7 hereditary spherocytosis 9.1 SEC23B PKLR PIEZO1

Graphical network of the top 20 diseases related to Epileptic Encephalopathy, Early Infantile, 50:



Diseases related to Epileptic Encephalopathy, Early Infantile, 50

Symptoms & Phenotypes for Epileptic Encephalopathy, Early Infantile, 50

Human phenotypes related to Epileptic Encephalopathy, Early Infantile, 50:

31 (show all 15)
# Description HPO Frequency HPO Source Accession
1 global developmental delay 31 HP:0001263
2 developmental regression 31 HP:0002376
3 anemia 31 HP:0001903
4 hyperammonemia 31 HP:0001987
5 acanthocytosis 31 HP:0001927
6 broad-based gait 31 HP:0002136
7 status epilepticus 31 HP:0002133
8 generalized hypotonia 31 HP:0001290
9 renal tubular acidosis 31 HP:0001947
10 brain atrophy 31 HP:0012444
11 poor speech 31 HP:0002465
12 anisopoikilocytosis 31 HP:0004823
13 epileptic encephalopathy 31 HP:0200134
14 abnormal glycosylation 31 HP:0012345
15 schistocytosis 31 HP:0001981

Symptoms via clinical synopsis from OMIM:

56
Hematology:
anemia
acanthocytosis
anisopoikilocytosis
schistocytosis
dyserythropoietic bone marrow biopsy

Laboratory Abnormalities:
serum transferrin glycosylation is normal
hyperammonemia, mild (patient a)
red blood cell proteins show abnormal glycosylation (patient a)

Genitourinary Kidneys:
renal tubular acidosis (patient a)

Neurologic Central Nervous System:
status epilepticus
poor speech
epileptic encephalopathy
hypotonia
seizures, refractory
more
Abdomen Gastrointestinal:
pan-disaccharidase deficiency (patient a)

Clinical features from OMIM:

616457

GenomeRNAi Phenotypes related to Epileptic Encephalopathy, Early Infantile, 50 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-159 9.28 CAD
2 Increased shRNA abundance (Z-score > 2) GR00366-A-208 9.28 SEC23B
3 Increased shRNA abundance (Z-score > 2) GR00366-A-27 9.28 SEC23B
4 Increased shRNA abundance (Z-score > 2) GR00366-A-5 9.28 CAD
5 Increased shRNA abundance (Z-score > 2) GR00366-A-51 9.28 CAD
6 Increased shRNA abundance (Z-score > 2) GR00366-A-89 9.28 CAD SEC23B
7 Increased shRNA abundance (Z-score > 2) GR00366-A-91 9.28 CAD
8 Increased shRNA abundance (Z-score > 2) GR00366-A-93 9.28 CAD

Drugs & Therapeutics for Epileptic Encephalopathy, Early Infantile, 50

Search Clinical Trials , NIH Clinical Center for Epileptic Encephalopathy, Early Infantile, 50

Genetic Tests for Epileptic Encephalopathy, Early Infantile, 50

Genetic tests related to Epileptic Encephalopathy, Early Infantile, 50:

# Genetic test Affiliating Genes
1 Epileptic Encephalopathy, Early Infantile, 50 29 CAD

Anatomical Context for Epileptic Encephalopathy, Early Infantile, 50

MalaCards organs/tissues related to Epileptic Encephalopathy, Early Infantile, 50:

40
Brain, Bone Marrow, Bone, Testes

Publications for Epileptic Encephalopathy, Early Infantile, 50

Articles related to Epileptic Encephalopathy, Early Infantile, 50:

# Title Authors PMID Year
1
CAD mutations and uridine-responsive epileptic encephalopathy. 6 56
28007989 2017
2
Biallelic mutations in CAD, impair de novo pyrimidine biosynthesis and decrease glycosylation precursors. 56 6
25678555 2015
3
Early infantile epileptic encephalopathy associated with a high voltage gated calcium channelopathy. 6
23339110 2013
4
Early forebrain wiring: genetic dissection using conditional Celsr3 mutant mice. 6
18487195 2008
5
Multi-gene panel testing improves diagnosis and management of patients with hereditary anemias. 61
29396846 2018

Variations for Epileptic Encephalopathy, Early Infantile, 50

ClinVar genetic disease variations for Epileptic Encephalopathy, Early Infantile, 50:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 CAD NM_004341.5(CAD):c.571C>T (p.Arg191Ter)SNV Pathogenic 801658 2:27445462-27445462 2:27222594-27222594
2 CAD NM_004341.5(CAD):c.1843-1G>ASNV Pathogenic 203465 rs769567624 2:27448998-27448998 2:27226130-27226130
3 CAD NM_004341.5(CAD):c.6071G>A (p.Arg2024Gln)SNV Pathogenic 203466 2:27464966-27464966 2:27242098-27242098
4 CAD NM_004341.5(CAD):c.5365C>T (p.Arg1789Ter)SNV Pathogenic 374831 rs62130681 2:27462310-27462310 2:27239442-27239442
5 CAD NM_004341.5(CAD):c.98T>G (p.Met33Arg)SNV Pathogenic/Likely pathogenic 374829 rs751610198 2:27440760-27440760 2:27217892-27217892
6 CAD NM_004341.5(CAD):c.1843-3C>TSNV Likely pathogenic 374830 rs1057519262 2:27448996-27448996 2:27226128-27226128
7 CAD NM_004341.5(CAD):c.5429G>A (p.Arg1810Gln)SNV Likely pathogenic 422220 rs139332887 2:27462599-27462599 2:27239731-27239731
8 CAD NM_004341.5(CAD):c.4930T>C (p.Phe1644Leu)SNV Likely benign 788724 2:27461368-27461368 2:27238500-27238500

UniProtKB/Swiss-Prot genetic disease variations for Epileptic Encephalopathy, Early Infantile, 50:

73
# Symbol AA change Variation ID SNP ID
1 CAD p.Arg2024Gln VAR_073955 rs763410987

Expression for Epileptic Encephalopathy, Early Infantile, 50

Search GEO for disease gene expression data for Epileptic Encephalopathy, Early Infantile, 50.

Pathways for Epileptic Encephalopathy, Early Infantile, 50

GO Terms for Epileptic Encephalopathy, Early Infantile, 50

Biological processes related to Epileptic Encephalopathy, Early Infantile, 50 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 metabolic process GO:0008152 8.62 PKLR CAD

Sources for Epileptic Encephalopathy, Early Infantile, 50

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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