Leukoencephalopathy, Progressive, Infantile-Onset, with or Without Deafness disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

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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:

MalaCards categories:
Global: Genetic diseases

See all MalaCards categories (disease lists)

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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.

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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

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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	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)

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

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

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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

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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

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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	Vargas A...Celis L	33260297	2020
2	Biallelic KARS pathogenic variants cause an early-onset progressive leukodystrophy. ⁵⁷	Itoh M...Kato Y	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	Ruzzenente B...Metodiev MD	30252186	2018
4	KARS-related diseases: progressive leukoencephalopathy with brainstem and spinal cord calcifications as new phenotype and a review of literature. ⁵⁷	Ardissone A...Ghezzi D	29615062	2018
5	Mutations in KARS cause early-onset hearing loss and leukoencephalopathy: Potential pathogenic mechanism. ⁵⁷	Zhou XL...Yang T	28887846	2017
6	A Comprehensive Genomic Analysis Reveals the Genetic Landscape of Mitochondrial Respiratory Chain Complex Deficiencies. ⁵⁷	Kohda M...Okazaki Y	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	McMillan HJ...Geraghty MT	25330800	2015
8	Progressive leukoencephalopathy with intracranial calcification, congenital deafness, and developmental deterioration. ⁵⁷	Kuki I...Itoh M	21964701	2011
9	Spinal cord calcification in an early-onset progressive leukoencephalopathy. ⁵⁷	Orcesi S...Balottin U	21427441	2011
10	A novel neurological disorder with progressive CNS calcification, deafness, renal tubular acidosis, and microcytic anemia. ⁵⁷	Yoshimura M...Takeshita K	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	Bakhvalov SA...Morozova OV	12924100	2003
12	Effects of metals on the total lipid content in the gypsy moth (Lymantria dispar, Lymantriidae, Lepid.) and its hemolymph. ⁶²	Ortel J	7579926	1995
13	Skin-piercing blood-sucking moths II: Studies on a further 3 adult Calyptra [Calpe] sp. (Lepid., Noctuidae). ⁶²	Banziger H	35931	1979
14	[Immunization experiments for producing antibody-like substances in caterpillars of Mamestra brassicae L. (Insecta, Lepid., Noct.)]. ⁶²	Luther P...Fischer G	1211001	1975
15	Skin-piercing blood-sucking moths I: ecological and ethological studies on Calpe eustrigata (Lepid., noctuidae). ⁶²	Banziger H	240258	1975
16	Insect neurometamorphosis. V. Fine structure of axons and neuroglia in the transforming interganglionic connectives of Galleria mellonella (L.) (Lepid optera). ⁶²	Tung AS...Pipa RL	4338500	1972
17	Lepid content of conidia of neurospora crassa. ⁶²	Bianchi DE...Turian G	6060645	1967
18	Observations on feeding habits of adult Westermanniinae (Lepid., Noctuidae) in Cambodia. ⁶²	BUETTIKER W	13805734	1959
19	Die Entwicklung des Genitalapparates bei triploiden Intersexen von Solenobia triquetrella F. R. (Lepid. Psychidae) Deutung des Intersexualitätsphänomens. ⁶²	Seiler J...Rainer M	28354755	1958
20	Die Fortpflanzungsbiologie der Solenobien (Lepid. psychidae), Verhalten bei Artkreuzungen und F1-Resultate. ⁶²	Seiler J...Puchta O	28354017	1956
21	[New chromosome formulas of the genus Erebia (Lepid. Rhopal)]. ⁶²	DE LESSE H	13107127	1953

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

Genes related to Leukoencephalopathy, Progressive, Infantile-Onset, with or Without Deafness (1 elite genes):

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubMed IDs
1	KARS1	Lysyl-TRNA Synthetase 1	Protein Coding	1308.29	Molecular basis known ⁵⁷ Pathogenic ⁵ Causative variation ⁷³ Genetic Tests ²⁸ GeneCards inferred via : Disorders (show sections)

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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

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

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

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

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

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

¹ BitterDB

² CDC

³ Cell Signaling Technology

⁴ ClinicalTrials

⁵ ClinVar

⁶ CNVD

⁷ Cochrane Library

⁸ Cosmic

⁹ dbSNP

¹⁰ DGIdb

¹¹ Disease Ontology

¹² diseasecard

¹³ DiseaseEnhancer

¹⁴ DISEASES

¹⁵ DrugBank

¹⁶ EFO

¹⁷ ExPASy

¹⁸ FMA

¹⁹ GARD

²⁰ GeneAnalytics

²¹ GeneCards

²² GeneGo (Thomson Reuters)

²³ GeneHancer via GeneCards

²⁴ GeneReviews

²⁵ GenomeRNAi

²⁶ GEO DataSets

²⁷ GO

²⁸ GTR

²⁹ HMDB

³⁰ HPO

³¹ ICD10

³² ICD10 via Orphanet

³³ ICD11

³⁴ ICD9CM

³⁵ IUPHAR

³⁶ LifeMap

³⁷ LncRNADisease

³⁸ LOVD

³⁹ MalaCards

⁴⁰ MedGen

⁴¹ MedlinePlus

⁴² MedlinePlus Genetics

⁴³ MeSH

⁴⁴ MESH via Orphanet

⁴⁵ MGI

⁴⁶ miR2Disease

⁴⁷ NCBI Bookshelf

⁴⁸ NCI

⁴⁹ NCIt

⁵⁰ NDF-RT

⁵¹ NIH Clinical Center

⁵² NINDS

⁵³ Novoseek

⁵⁴ Novus Biologicals

⁵⁵ ODiseA

⁵⁶ OMIM via Orphanet

⁵⁷ OMIM® (Updated 08-Dec-2022)

⁵⁸ Orphanet

⁵⁹ PathCards

⁶⁰ PharmGKB

⁶¹ PubChem

⁶² PubMed

⁶³ PubMed Health

⁶⁴ QIAGEN

⁶⁵ R&D Systems

⁶⁶ Reactome

⁶⁷ Sino Biological

⁶⁸ SNOMED-CT

⁶⁹ SNOMED-CT via HPO

⁷⁰ Tocris

⁷¹ UMLS

⁷² UMLS via Orphanet

⁷³ UniProtKB/Swiss-Prot

⁷⁴ WikiPathways

⁷⁵ Wikipedia

LEPID MCID: LKN032 MIFTS: 26	Leukoencephalopathy, Progressive, Infantile-Onset, with or Without Deafness (LEPID) Categories: Genetic diseases	Data Licensing For inquiries, contact: [email protected]
Genes Variations Tissues Related diseases Publications Symptoms & Phenotypes Expand all tables

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

Aliases & Classifications for Leukoencephalopathy, Progressive, Infantile-Onset, with or...

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

Characteristics:

Inheritance:

OMIM®:

Classifications:

External Ids:

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

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:

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

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

Symptoms via clinical synopsis from OMIM®:

Clinical features from OMIM®:

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

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

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

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

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

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

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

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

Genes related to Leukoencephalopathy, Progressive, Infantile-Onset, with or Without Deafness (1 elite genes):

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

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

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

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

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...