LEPID
MCID: LKN032
MIFTS: 26

Leukoencephalopathy, Progressive, Infantile-Onset, with or Without Deafness (LEPID)

Categories: Genetic diseases
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Aliases & Classifications for Leukoencephalopathy, Progressive, Infantile-Onset, with or...

MalaCards integrated aliases for Leukoencephalopathy, Progressive, Infantile-Onset, with or Without Deafness:

Name: Leukoencephalopathy, Progressive, Infantile-Onset, with or Without Deafness 57 73 28 5
Lepid 57 73
Leukoencephalopathy, Progressive, Infantile-Onset, with/without Deafness 38

Characteristics:


Inheritance:

Autosomal recessive 57

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
progressive disorder
onset in infancy or early childhood
neurologic regression associated with infection or fever
premature death is common


Classifications:



Summaries for Leukoencephalopathy, Progressive, Infantile-Onset, with or...

OMIM®: 57 Infantile-onset progressive leukoencephalopathy with or without deafness (LEPID) is an autosomal recessive complex neurodegenerative disorder with onset of symptoms in infancy or early childhood. Most patients present with sensorineural deafness or hypoacousia and global developmental delay. Affected individuals show episodic regression with progressive motor deterioration resulting in spastic tetraplegia and loss of ambulation, as well as impaired intellectual development with poor or absent speech. Additional more variable features may include poor overall growth with microcephaly, seizures, visual loss, microcytic anemia, and hepatic enlargement or abnormal liver enzymes. Brain imaging shows deep white matter abnormalities consistent with a progressive leukoencephalopathy. The brain and spinal cord are usually both involved; calcifications of these regions are often observed. Laboratory studies show increased serum lactate and deficiencies of mitochondrial respiratory chain complexes, consistent with global mitochondrial dysfunction. Early death often occurs (summary by Itoh et al., 2019). (619147) (Updated 08-Dec-2022)

MalaCards based summary: Leukoencephalopathy, Progressive, Infantile-Onset, with or Without Deafness, also known as lepid, is related to hereditary mixed polyposis syndrome and eye disease. An important gene associated with Leukoencephalopathy, Progressive, Infantile-Onset, with or Without Deafness is KARS1 (Lysyl-TRNA Synthetase 1). Affiliated tissues include spinal cord, liver and brain, and related phenotypes are failure to thrive and nystagmus

UniProtKB/Swiss-Prot: 73 An autosomal recessive, complex neurodegenerative disorder apparent from infancy. LEPID is characterized by early-onset progressive leukoencephalopathy with brainstem and spinal cord calcifications, sensorineural deafness in most patients, global developmental delay with cognitive impairment and poor or absent speech, developmental regression, and neurologic deterioration. Additional more variable features may include poor overall growth with microcephaly, seizures, visual loss, microcytic anemia, and hepatic enlargement or abnormal liver enzymes. Premature death is common.

Related Diseases for Leukoencephalopathy, Progressive, Infantile-Onset, with or...

Diseases related to Leukoencephalopathy, Progressive, Infantile-Onset, with or Without Deafness via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 hereditary mixed polyposis syndrome 10.0
2 eye disease 10.0

Symptoms & Phenotypes for Leukoencephalopathy, Progressive, Infantile-Onset, with or...

Human phenotypes related to Leukoencephalopathy, Progressive, Infantile-Onset, with or Without Deafness:

30 (show all 32)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 failure to thrive 30 Very rare (1%) HP:0001508
2 nystagmus 30 Very rare (1%) HP:0000639
3 cerebral calcification 30 Very rare (1%) HP:0002514
4 hypothyroidism 30 Very rare (1%) HP:0000821
5 hypotonia 30 Very rare (1%) HP:0001252
6 developmental regression 30 Very rare (1%) HP:0002376
7 global developmental delay 30 Very rare (1%) HP:0001263
8 delayed skeletal maturation 30 Very rare (1%) HP:0002750
9 microcephaly 30 Very rare (1%) HP:0000252
10 vomiting 30 Very rare (1%) HP:0002013
11 renal insufficiency 30 Very rare (1%) HP:0000083
12 spastic tetraplegia 30 Very rare (1%) HP:0002510
13 absent speech 30 Very rare (1%) HP:0001344
14 growth delay 30 Very rare (1%) HP:0001510
15 narrow mouth 30 Very rare (1%) HP:0000160
16 long philtrum 30 Very rare (1%) HP:0000343
17 increased serum lactate 30 Very rare (1%) HP:0002151
18 hypospadias 30 Very rare (1%) HP:0000047
19 severe global developmental delay 30 Very rare (1%) HP:0011344
20 congenital sensorineural hearing impairment 30 Very rare (1%) HP:0008527
21 leukoencephalopathy 30 Very rare (1%) HP:0002352
22 increased serum pyruvate 30 Very rare (1%) HP:0003542
23 small for gestational age 30 Very rare (1%) HP:0001518
24 hyperalaninemia 30 Very rare (1%) HP:0003348
25 akinesia 30 Very rare (1%) HP:0002304
26 hypochromic microcytic anemia 30 Very rare (1%) HP:0004840
27 ketosis 30 Very rare (1%) HP:0001946
28 decreased activity of mitochondrial respiratory chain 30 Very rare (1%) HP:0008972
29 decreased csf biopterin level 30 Very rare (1%) HP:0040209
30 delayed ability to walk 30 Very rare (1%) HP:0031936
31 mild proteinuria 30 Very rare (1%) HP:0012595
32 generalized tonic seizure 30 Very rare (1%) HP:0010818

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Growth Other:
failure to thrive
poor overall growth

Neurologic Central Nervous System:
developmental regression
global developmental delay
seizures
impaired intellectual development
cortical atrophy
more
Hematology:
microcytic anemia

Abdomen Gastrointestinal:
feeding difficulties

Head And Neck Ears:
sensorineural deafness

Cardiovascular Heart:
hypertrophic cardiomyopathy (in some patients)

Head And Neck Face:
dysmorphic facial features, nonspecific

Head And Neck Eyes:
nystagmus
poor visual fixation
visual impairment (in some patients)

Abdomen Liver:
hepatomegaly

Laboratory Abnormalities:
increased serum lactate
increased serum pyruvate
abnormal liver enzymes (in some patients)
decreased activities of mitochondrial respiratory enzyme complexes

Metabolic Features:
metabolic acidosis

Head And Neck Head:
microcephaly (in some patients)

Genitourinary Kidneys:
renal tubular acidosis (in some patients)

Clinical features from OMIM®:

619147 (Updated 08-Dec-2022)

Drugs & Therapeutics for Leukoencephalopathy, Progressive, Infantile-Onset, with or...

Search Clinical Trials, NIH Clinical Center for Leukoencephalopathy, Progressive, Infantile-Onset, with or Without Deafness

Genetic Tests for Leukoencephalopathy, Progressive, Infantile-Onset, with or...

Genetic tests related to Leukoencephalopathy, Progressive, Infantile-Onset, with or Without Deafness:

# Genetic test Affiliating Genes
1 Leukoencephalopathy, Progressive, Infantile-Onset, with or Without Deafness 28 KARS1

Anatomical Context for Leukoencephalopathy, Progressive, Infantile-Onset, with or...

Organs/tissues related to Leukoencephalopathy, Progressive, Infantile-Onset, with or Without Deafness:

MalaCards : Spinal Cord, Liver, Brain, Skin

Publications for Leukoencephalopathy, Progressive, Infantile-Onset, with or...

Articles related to Leukoencephalopathy, Progressive, Infantile-Onset, with or Without Deafness:

(show all 21)
# Title Authors PMID Year
1
Progressive Early-Onset Leukodystrophy Related to Biallelic Variants in the KARS Gene: The First Case Described in Latin America. 57
33260297 2020
2
Biallelic KARS pathogenic variants cause an early-onset progressive leukodystrophy. 57
30715177 2019
3
Inhibition of mitochondrial translation in fibroblasts from a patient expressing the KARS p.(Pro228Leu) variant and presenting with sensorineural deafness, developmental delay, and lactic acidosis. 57
30252186 2018
4
KARS-related diseases: progressive leukoencephalopathy with brainstem and spinal cord calcifications as new phenotype and a review of literature. 57
29615062 2018
5
Mutations in KARS cause early-onset hearing loss and leukoencephalopathy: Potential pathogenic mechanism. 57
28887846 2017
6
A Comprehensive Genomic Analysis Reveals the Genetic Landscape of Mitochondrial Respiratory Chain Complex Deficiencies. 57
26741492 2016
7
Congenital Visual Impairment and Progressive Microcephaly Due to Lysyl-Transfer Ribonucleic Acid (RNA) Synthetase (KARS) Mutations: The Expanding Phenotype of Aminoacyl-Transfer RNA Synthetase Mutations in Human Disease. 57
25330800 2015
8
Progressive leukoencephalopathy with intracranial calcification, congenital deafness, and developmental deterioration. 57
21964701 2011
9
Spinal cord calcification in an early-onset progressive leukoencephalopathy. 57
21427441 2011
10
A novel neurological disorder with progressive CNS calcification, deafness, renal tubular acidosis, and microcytic anemia. 57
9112970 1997
11
[Connection of virus carriage and acute infection, caused by nuclear polyhedrosis virus in native populations of silkworm (Lymantria dispar L., Lym. Lepid.)]. 62
12924100 2003
12
Effects of metals on the total lipid content in the gypsy moth (Lymantria dispar, Lymantriidae, Lepid.) and its hemolymph. 62
7579926 1995
13
Skin-piercing blood-sucking moths II: Studies on a further 3 adult Calyptra [Calpe] sp. (Lepid., Noctuidae). 62
35931 1979
14
[Immunization experiments for producing antibody-like substances in caterpillars of Mamestra brassicae L. (Insecta, Lepid., Noct.)]. 62
1211001 1975
15
Skin-piercing blood-sucking moths I: ecological and ethological studies on Calpe eustrigata (Lepid., noctuidae). 62
240258 1975
16
Insect neurometamorphosis. V. Fine structure of axons and neuroglia in the transforming interganglionic connectives of Galleria mellonella (L.) (Lepid optera). 62
4338500 1972
17
Lepid content of conidia of neurospora crassa. 62
6060645 1967
18
Observations on feeding habits of adult Westermanniinae (Lepid., Noctuidae) in Cambodia. 62
13805734 1959
19
Die Entwicklung des Genitalapparates bei triploiden Intersexen von Solenobia triquetrella F. R. (Lepid. Psychidae) Deutung des Intersexualitätsphänomens. 62
28354755 1958
20
Die Fortpflanzungsbiologie der Solenobien (Lepid. psychidae), Verhalten bei Artkreuzungen und F1-Resultate. 62
28354017 1956
21
[New chromosome formulas of the genus Erebia (Lepid. Rhopal)]. 62
13107127 1953

Variations for Leukoencephalopathy, Progressive, Infantile-Onset, with or...

ClinVar genetic disease variations for Leukoencephalopathy, Progressive, Infantile-Onset, with or Without Deafness:

5
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 KARS1 NM_005548.3(KARS1):c.1312C>T (p.Arg438Trp) SNV Pathogenic
997976 rs761527468 GRCh37: 16:75665092-75665092
GRCh38: 16:75631194-75631194
2 KARS1 NM_005548.3(KARS1):c.1573G>A (p.Glu525Lys) SNV Pathogenic
997977 rs770522582 GRCh37: 16:75662589-75662589
GRCh38: 16:75628691-75628691
3 KARS1 NM_005548.3(KARS1):c.433T>C (p.Tyr145His) SNV Uncertain Significance
60752 rs397514745 GRCh37: 16:75670401-75670401
GRCh38: 16:75636503-75636503
4 KARS1 NM_005548.3(KARS1):c.1181T>A (p.Ile394Asn) SNV Uncertain Significance
1679325 GRCh37: 16:75665385-75665385
GRCh38: 16:75631487-75631487

UniProtKB/Swiss-Prot genetic disease variations for Leukoencephalopathy, Progressive, Infantile-Onset, with or Without Deafness:

73
# Symbol AA change Variation ID SNP ID
1 KARS1 p.Arg477His VAR_079744 rs778748895
2 KARS1 p.Gly189Asp VAR_085387
3 KARS1 p.Pro200Leu VAR_085388
4 KARS1 p.Leu568Phe VAR_085391

Expression for Leukoencephalopathy, Progressive, Infantile-Onset, with or...

Search GEO for disease gene expression data for Leukoencephalopathy, Progressive, Infantile-Onset, with or Without Deafness.

Pathways for Leukoencephalopathy, Progressive, Infantile-Onset, with or...

GO Terms for Leukoencephalopathy, Progressive, Infantile-Onset, with or...

Sources for Leukoencephalopathy, Progressive, Infantile-Onset, with or...

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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