Leukodystrophy, Progressive, Early Childhood-Onset disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

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Aliases & Classifications for Leukodystrophy, Progressive, Early Childhood-Onset

MalaCards integrated aliases for Leukodystrophy, Progressive, Early Childhood-Onset:

Name: Leukodystrophy, Progressive, Early Childhood-Onset ⁵⁷ ⁷²

Alkaline Ceramidase 3 Deficiency ⁵⁸ ⁶

Pldeco ⁵⁷ ⁷²

Acer3-Related Early Childhood-Onset Progressive Leukodystrophy ⁵⁸

Leukodystrophy Due to Alkaline Ceramidase 3 Deficiency ⁵⁸

Early Childhood-Onset Progressive Leukodystrophy ³⁶

Characteristics:

OMIM®:

⁵⁷ (Updated 05-Apr-2021)

Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
onset between 6 and 12 months of age
patients are severely impaired, needing mechanical ventilation and feeding tube
two sibs of ashkenazi jewish descent have been reported (last curated november 2017)

HPO:

³¹

leukodystrophy, progressive, early childhood-onset:
Inheritance autosomal recessive inheritance
Onset and clinical course progressive

Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases
Anatomical: Neuronal diseases

See all MalaCards categories (disease lists)

Orphanet: ⁵⁸

Rare neurological diseases

External Ids:

OMIM® ⁵⁷ 617762

KEGG ³⁶ H02468

MeSH ⁴⁴ D020279

Orphanet ⁵⁸ ORPHA502444

MedGen ⁴¹ C4540358 CN603947

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Summaries for Leukodystrophy, Progressive, Early Childhood-Onset

UniProtKB/Swiss-Prot : ⁷² Leukodystrophy, progressive, early childhood-onset: A form of leukodystrophy, a disorder of myelin production or maintenance affecting the central nervous system. PELCO features include neurological regression between 6 and 13 months of age, truncal hypotonia, appendicular spasticity, dystonia, optic disk pallor, peripheral neuropathy and neurogenic bladder. Brain imaging shows progressive diffuse abnormal white matter signals, cerebral atrophy, and thin corpus callosum. Sural nerve biopsy shows decreased myelination. PLDECO inheritance is autosomal recessive.

MalaCards based summary : Leukodystrophy, Progressive, Early Childhood-Onset, also known as alkaline ceramidase 3 deficiency, is related to ataxia and polyneuropathy, adult-onset and colitis. An important gene associated with Leukodystrophy, Progressive, Early Childhood-Onset is ACER3 (Alkaline Ceramidase 3), and among its related pathways/superpathways is Sphingolipid metabolism. Affiliated tissues include brain, and related phenotypes are intellectual disability and spasticity

KEGG : ³⁶ Early childhood-onset progressive leukodystrophy (PLDECO) is a rare autosomal recessive disorder caused by deficiency of the alkaline ceramidase. Mutations in the ACER3 gene result in inactivation of ACER3, leading to the accumulation of various sphingolipids in blood and probably in brain.

More information from OMIM: 617762

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Related Diseases for Leukodystrophy, Progressive, Early Childhood-Onset

Diseases related to Leukodystrophy, Progressive, Early Childhood-Onset via text searches within MalaCards or GeneCards Suite gene sharing:

#	Related Disease	Score	Top Affiliating Genes
1	ataxia and polyneuropathy, adult-onset	10.3
2	colitis	10.1

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Symptoms & Phenotypes for Leukodystrophy, Progressive, Early Childhood-Onset

Human phenotypes related to Leukodystrophy, Progressive, Early Childhood-Onset:

³¹ (show all 22)

#	Description	HPO Source Accession
1	intellectual disability ³¹	HP:0001249
2	spasticity ³¹	HP:0001257
3	developmental regression ³¹	HP:0002376
4	coarse facial features ³¹	HP:0000280
5	smooth philtrum ³¹	HP:0000319
6	thick eyebrow ³¹	HP:0000574
7	short stature ³¹	HP:0004322
8	flexion contracture ³¹	HP:0001371
9	thick lower lip vermilion ³¹	HP:0000179
10	developmental stagnation ³¹	HP:0007281
11	low-set ears ³¹	HP:0000369
12	areflexia ³¹	HP:0001284
13	dystonia ³¹	HP:0001332
14	peripheral neuropathy ³¹	HP:0009830
15	sloping forehead ³¹	HP:0000340
16	hypoplasia of the corpus callosum ³¹	HP:0002079
17	optic disc pallor ³¹	HP:0000543
18	leukodystrophy ³¹	HP:0002415
19	prominent nose ³¹	HP:0000448
20	cerebral atrophy ³¹	HP:0002059
21	relative macrocephaly ³¹	HP:0004482
22	neurogenic bladder ³¹	HP:0000011

Symptoms via clinical synopsis from OMIM®:

⁵⁷ (Updated 05-Apr-2021)

Neurologic Central Nervous System:
intellectual disability
spasticity
developmental regression
developmental stagnation
dystonia
more

Growth Height:
short stature

Neurologic Peripheral Nervous System:
areflexia
peripheral neuropathy
sural nerve biopsy shows decreased myelination

Head And Neck Nose:
prominent nose

Head And Neck Head:
macrocephaly, relative

Muscle Soft Tissue:
hypotonia, axial

Laboratory Abnormalities:
increased plasma levels of certain ceramides
increased plasma levels of complex sphingolipids

Head And Neck Face:
coarse facial features
sloping forehead
flat philtrum

Head And Neck Ears:
low-set ears

Head And Neck Eyes:
optic disc pallor
thick eyebrows

Genitourinary Bladder:
neurogenic bladder

Skeletal:
contractures

Head And Neck Mouth:
prominent lower lip

Clinical features from OMIM®:

617762 (Updated 05-Apr-2021)

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Drugs & Therapeutics for Leukodystrophy, Progressive, Early Childhood-Onset

Search Clinical Trials , NIH Clinical Center for Leukodystrophy, Progressive, Early Childhood-Onset

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Genetic Tests for Leukodystrophy, Progressive, Early Childhood-Onset

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Anatomical Context for Leukodystrophy, Progressive, Early Childhood-Onset

MalaCards organs/tissues related to Leukodystrophy, Progressive, Early Childhood-Onset:

⁴⁰

Brain

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Publications for Leukodystrophy, Progressive, Early Childhood-Onset

Articles related to Leukodystrophy, Progressive, Early Childhood-Onset:

#	Title	Authors	PMID	Year
1	Deficiency of the alkaline ceramidase ACER3 manifests in early childhood by progressive leukodystrophy. ⁶ ⁵⁷	Edvardson S...Elpeleg O	26792856	2016
2	Correction: Alkaline Ceramidase 3 Deficiency Results in Purkinje Cell Degeneration and Cerebellar Ataxia Due to Dyshomeostasis of Sphingolipids in the Brain. ⁶¹	Wang K...Mao C	29360825	2018
3	Alkaline ceramidase 3 deficiency aggravates colitis and colitis-associated tumorigenesis in mice by hyperactivating the innate immune system. ⁶¹	Wang K...Mao C	26938296	2016
4	Alkaline Ceramidase 3 Deficiency Results in Purkinje Cell Degeneration and Cerebellar Ataxia Due to Dyshomeostasis of Sphingolipids in the Brain. ⁶¹	Wang K...Mao C	26474409	2015

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Genes for Leukodystrophy, Progressive, Early Childhood-Onset

Genes related to Leukodystrophy, Progressive, Early Childhood-Onset (1 elite genes):

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubMed IDs
1	ACER3	Alkaline Ceramidase 3	Protein Coding	1641.69	Molecular basis known ⁵⁷ Pathogenic ⁶ Causative germline mutation ⁵⁸ Causative variation ⁷² Unconfirmed association ⁵⁷ Likely pathogenic ⁶ GeneCards inferred via : Disorders Variants (show sections)	26792856

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Variations for Leukodystrophy, Progressive, Early Childhood-Onset

ClinVar genetic disease variations for Leukodystrophy, Progressive, Early Childhood-Onset:

⁶

#	Gene	Name	Type	Significance	ClinVarId	dbSNP ID	Position
1	ACER3	NM_018367.7(ACER3):c.98A>G (p.Glu33Gly)	SNV	Pathogenic	446204	rs1554988032	GRCh37: 11:76572118-76572118 GRCh38: 11:76861074-76861074
2	ACER3	NM_018367.7(ACER3):c.607C>T (p.Arg203Ter)	SNV	Pathogenic	548629	rs782709009	GRCh37: 11:76727726-76727726 GRCh38: 11:77016682-77016682
3	ACER3	NM_018367.7(ACER3):c.566G>A (p.Trp189Ter)	SNV	Pathogenic	996745		GRCh37: 11:76726128-76726128 GRCh38: 11:77015084-77015084
4	ACER3	NM_018367.7(ACER3):c.587G>A (p.Cys196Tyr)	SNV	Pathogenic	1030362		GRCh37: 11:76726149-76726149 GRCh38: 11:77015105-77015105
5	ACER3	NM_018367.7(ACER3):c.475C>T (p.Arg159Ter)	SNV	Likely pathogenic	928843		GRCh37: 11:76709843-76709843 GRCh38: 11:76998799-76998799
6	ACER3	NM_018367.7(ACER3):c.292T>C (p.Tyr98His)	SNV	Uncertain significance	988591		GRCh37: 11:76687357-76687357 GRCh38: 11:76976313-76976313
7	ACER3	NM_018367.7(ACER3):c.53T>C (p.Leu18Pro)	SNV	Uncertain significance	988663		GRCh37: 11:76572073-76572073 GRCh38: 11:76861029-76861029

UniProtKB/Swiss-Prot genetic disease variations for Leukodystrophy, Progressive, Early Childhood-Onset:

⁷²

#	Symbol	AA change	Variation ID	SNP ID
1	ACER3	p.Glu33Gly	VAR_081205	rs155498803

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Expression for Leukodystrophy, Progressive, Early Childhood-Onset

Search GEO for disease gene expression data for Leukodystrophy, Progressive, Early Childhood-Onset.

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Pathways for Leukodystrophy, Progressive, Early Childhood-Onset

Pathways related to Leukodystrophy, Progressive, Early Childhood-Onset according to KEGG:

³⁶

#	Name	Kegg Source Accession
1	Sphingolipid metabolism	hsa00600

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GO Terms for Leukodystrophy, Progressive, Early Childhood-Onset

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Sources for Leukodystrophy, Progressive, Early Childhood-Onset

¹ BioSystems

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⁵ ClinicalTrials

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²⁴ GeneHancer via GeneCards

²⁵ GeneReviews

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²⁷ GEO DataSets

²⁸ GO

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³⁰ HMDB

³¹ HPO

³² ICD10

³³ ICD10 via Orphanet

³⁴ ICD9CM

³⁵ IUPHAR

³⁶ KEGG

³⁷ LifeMap

³⁸ LncRNADisease

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⁴⁰ MalaCards

⁴¹ MedGen

⁴² MedlinePlus

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⁴⁴ MeSH

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⁵² NIH Clinical Center

⁵³ NINDS

⁵⁴ Novoseek

⁵⁵ Novus Biologicals

⁵⁶ OMIM via Orphanet

⁵⁷ OMIM® (Updated 05-Apr-2021)

⁵⁸ Orphanet

⁵⁹ PathCards

⁶⁰ PharmGKB

⁶¹ PubMed

⁶² PubMed Health

⁶³ QIAGEN

⁶⁴ R&D Systems

⁶⁵ Reactome

⁶⁶ Sino Biological

⁶⁷ SNOMED-CT

⁶⁸ SNOMED-CT via HPO

⁶⁹ Tocris

⁷⁰ UMLS

⁷¹ UMLS via Orphanet

⁷² UniProtKB/Swiss-Prot

⁷³ Wikipedia

Leukodystrophy, Progressive, Early Childhood-Onset (PLDECO)

Aliases & Classifications for Leukodystrophy, Progressive, Early Childhood-Onset

MalaCards integrated aliases for Leukodystrophy, Progressive, Early Childhood-Onset:

Characteristics:

OMIM®:

HPO:

Classifications:

External Ids:

Summaries for Leukodystrophy, Progressive, Early Childhood-Onset

Related Diseases for Leukodystrophy, Progressive, Early Childhood-Onset

Diseases related to Leukodystrophy, Progressive, Early Childhood-Onset via text searches within MalaCards or GeneCards Suite gene sharing:

Symptoms & Phenotypes for Leukodystrophy, Progressive, Early Childhood-Onset

Human phenotypes related to Leukodystrophy, Progressive, Early Childhood-Onset:

Symptoms via clinical synopsis from OMIM®:

Clinical features from OMIM®:

Drugs & Therapeutics for Leukodystrophy, Progressive, Early Childhood-Onset

Genetic Tests for Leukodystrophy, Progressive, Early Childhood-Onset

Anatomical Context for Leukodystrophy, Progressive, Early Childhood-Onset

MalaCards organs/tissues related to Leukodystrophy, Progressive, Early Childhood-Onset:

Publications for Leukodystrophy, Progressive, Early Childhood-Onset

Articles related to Leukodystrophy, Progressive, Early Childhood-Onset:

Genes for Leukodystrophy, Progressive, Early Childhood-Onset

Genes related to Leukodystrophy, Progressive, Early Childhood-Onset (1 elite genes):

Variations for Leukodystrophy, Progressive, Early Childhood-Onset

ClinVar genetic disease variations for Leukodystrophy, Progressive, Early Childhood-Onset:

UniProtKB/Swiss-Prot genetic disease variations for Leukodystrophy, Progressive, Early Childhood-Onset:

Expression for Leukodystrophy, Progressive, Early Childhood-Onset

Pathways for Leukodystrophy, Progressive, Early Childhood-Onset

Pathways related to Leukodystrophy, Progressive, Early Childhood-Onset according to KEGG:

GO Terms for Leukodystrophy, Progressive, Early Childhood-Onset

Sources for Leukodystrophy, Progressive, Early Childhood-Onset