PLDECO
MCID: LKD026
MIFTS: 26

Leukodystrophy, Progressive, Early Childhood-Onset (PLDECO)

Categories: Eye diseases, Genetic diseases, Nephrological diseases, Neuronal diseases, Rare diseases
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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 73 38
Alkaline Ceramidase 3 Deficiency 58 28 5
Pldeco 57 73
Acer3-Related Early Childhood-Onset Progressive Leukodystrophy 58
Leukodystrophy Due to Alkaline Ceramidase 3 Deficiency 58

Characteristics:


Inheritance:

Autosomal recessive 57

Prevelance:

Alkaline Ceramidase 3 Deficiency: <1/1000000 (Worldwide) 58

Age Of Onset:

Alkaline Ceramidase 3 Deficiency: Infancy 58

OMIM®:

57 (Updated 08-Dec-2022)
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:

30
leukodystrophy, progressive, early childhood-onset:
Onset and clinical course progressive


Classifications:

Orphanet: 58  
Rare neurological diseases


Summaries for Leukodystrophy, Progressive, Early Childhood-Onset

Orphanet: 58 A rare genetic leukodystrophy characterized by infantile onset of stagnation and regression of motor and language development resulting in complete lack of communication and purposeful movement. Further neurological manifestations include truncal hypotonia, appendicular spasticity, dystonia, optic disc pallor, peripheral neuropathy, and neurogenic bladder. Patients also present multiple contractures, late-onset relative macrocephaly, short stature, and facial dysmorphism (including coarse facial features, sloping forehead, thick eyebrows, low-set ears, prominent nose, flat philtrum, and prominent lower lip). Brain imaging at advanced stages shows diffuse abnormal white matter signal and severe atrophy. Sural nerve biopsy reveals decreased myelination.

MalaCards based summary: Leukodystrophy, Progressive, Early Childhood-Onset, also known as alkaline ceramidase 3 deficiency, is related to aceruloplasminemia and colitis. An important gene associated with Leukodystrophy, Progressive, Early Childhood-Onset is ACER3 (Alkaline Ceramidase 3). Affiliated tissues include brain, and related phenotypes are intellectual disability and spasticity

UniProtKB/Swiss-Prot: 73 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.

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 aceruloplasminemia 10.3
2 colitis 10.1

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

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

30 (show all 22)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 30 HP:0001249
2 spasticity 30 HP:0001257
3 developmental regression 30 HP:0002376
4 coarse facial features 30 HP:0000280
5 smooth philtrum 30 HP:0000319
6 thick eyebrow 30 HP:0000574
7 short stature 30 HP:0004322
8 flexion contracture 30 HP:0001371
9 thick lower lip vermilion 30 HP:0000179
10 developmental stagnation 30 HP:0007281
11 low-set ears 30 HP:0000369
12 areflexia 30 HP:0001284
13 dystonia 30 HP:0001332
14 peripheral neuropathy 30 HP:0009830
15 sloping forehead 30 HP:0000340
16 optic disc pallor 30 HP:0000543
17 leukodystrophy 30 HP:0002415
18 prominent nose 30 HP:0000448
19 cerebral atrophy 30 HP:0002059
20 relative macrocephaly 30 HP:0004482
21 hypoplasia of the corpus callosum 30 HP:0002079
22 neurogenic bladder 30 HP:0000011

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
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 08-Dec-2022)

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

Genetic tests related to Leukodystrophy, Progressive, Early Childhood-Onset:

# Genetic test Affiliating Genes
1 Alkaline Ceramidase 3 Deficiency 28 ACER3

Anatomical Context for Leukodystrophy, Progressive, Early Childhood-Onset

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

MalaCards : 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. 57 5
26792856 2016
2
Correction: Alkaline Ceramidase 3 Deficiency Results in Purkinje Cell Degeneration and Cerebellar Ataxia Due to Dyshomeostasis of Sphingolipids in the Brain. 62
29360825 2018
3
Alkaline ceramidase 3 deficiency aggravates colitis and colitis-associated tumorigenesis in mice by hyperactivating the innate immune system. 62
26938296 2016
4
Alkaline Ceramidase 3 Deficiency Results in Purkinje Cell Degeneration and Cerebellar Ataxia Due to Dyshomeostasis of Sphingolipids in the Brain. 62
26474409 2015

Variations for Leukodystrophy, Progressive, Early Childhood-Onset

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

5
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ACER3 NM_018367.7(ACER3):c.566G>A (p.Trp189Ter) SNV Pathogenic
996745 rs1949342923 GRCh37: 11:76726128-76726128
GRCh38: 11:77015084-77015084
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.587G>A (p.Cys196Tyr) SNV Pathogenic
1030362 rs782435086 GRCh37: 11:76726149-76726149
GRCh38: 11:77015105-77015105
4 ACER3 NM_018367.7(ACER3):c.98A>G (p.Glu33Gly) SNV Pathogenic
446204 rs1554988032 GRCh37: 11:76572118-76572118
GRCh38: 11:76861074-76861074
5 ACER3 NM_018367.7(ACER3):c.475C>T (p.Arg159Ter) SNV Likely Pathogenic
928843 rs782329790 GRCh37: 11:76709843-76709843
GRCh38: 11:76998799-76998799
6 ACER3 NM_018367.7(ACER3):c.292T>C (p.Tyr98His) SNV Uncertain Significance
988591 rs1948442632 GRCh37: 11:76687357-76687357
GRCh38: 11:76976313-76976313
7 ACER3 NM_018367.7(ACER3):c.53T>C (p.Leu18Pro) SNV Uncertain Significance
988663 rs1944923735 GRCh37: 11:76572073-76572073
GRCh38: 11:76861029-76861029
8 ACER3 NM_018367.7(ACER3):c.238T>C (p.Phe80Leu) SNV Uncertain Significance
1236177 GRCh37: 11:76670046-76670046
GRCh38: 11:76959002-76959002

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

73
# Symbol AA change Variation ID SNP ID
1 ACER3 p.Glu33Gly VAR_081205 rs1554988032

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

GO Terms for Leukodystrophy, Progressive, Early Childhood-Onset

Sources for Leukodystrophy, Progressive, Early Childhood-Onset

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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