PLDECO
MCID: LKD026
MIFTS: 24

Leukodystrophy, Progressive, Early Childhood-Onset (PLDECO)

Categories: Genetic diseases, Neuronal diseases, Rare diseases

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:

Orphanet: 58  
Rare neurological diseases


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

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

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

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

31 (show all 22)
# Description HPO Frequency 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)

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

Search Clinical Trials , NIH Clinical Center 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:

40
Brain

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
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
29360825 2018
3
Alkaline ceramidase 3 deficiency aggravates colitis and colitis-associated tumorigenesis in mice by hyperactivating the innate immune system. 61
26938296 2016
4
Alkaline Ceramidase 3 Deficiency Results in Purkinje Cell Degeneration and Cerebellar Ataxia Due to Dyshomeostasis of Sphingolipids in the Brain. 61
26474409 2015

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

Expression for Leukodystrophy, Progressive, Early Childhood-Onset

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

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

GO Terms for Leukodystrophy, Progressive, Early Childhood-Onset

Sources for Leukodystrophy, Progressive, Early Childhood-Onset

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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