MLD
MCID: MTC003
MIFTS: 70

Metachromatic Leukodystrophy (MLD) malady

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Eye diseases, Metabolic diseases

Aliases & Classifications for Metachromatic Leukodystrophy

Aliases & Descriptions for Metachromatic Leukodystrophy:

Name: Metachromatic Leukodystrophy 54 38 12 23 50 24 25 51 56 13 14
Arylsulfatase a Deficiency 12 23 50 24 56 66 69
Mld 12 50 24 25 56 66
Arsa Deficiency 23 50 24 25 66
Leukodystrophy Metachromatic 50 66 29 52
Sulfatide Lipidosis 50 25 66
Cerebral Sclerosis Diffuse Metachromatic Form 50 66
Metachromatic Leukoencephalopathy 50 25
Cerebroside Sulfatase Deficiency 50 66
Leukodystrophy, Metachromatic 42 69
Sulfatidosis 25 69
Cerebral Sclerosis, Diffuse, Metachromatic Form 25
Metachromatic Leukodystrophy Late Infantile 66
Leukodystrophy Metachromatic Late Infantile 52
Cerebroside Sulphatase Deficiency Disease 25
Metachromatic Leukodystrophy Juvenile 66
Leukodystrophy Metachromatic Juvenile 52
Metachromatic Leukodystrophy, Infant 69
Deficiency of Cerebroside-Sulfatase 12
Arylsulfatase a Deficiency Disease 25
Metachromatic Leukodystrophy Adult 66
Leukodystrophy Metachromatic Adult 52
Scholz Cerebral Sclerosis 12
Sulfatide Lipoidosis 12
Greenfield Disease 25
Arylsulfatase a 13

Characteristics:

Orphanet epidemiological data:

56
metachromatic leukodystrophy
Inheritance: Autosomal recessive; Prevalence: 1-9/100000 (Europe),1-9/1000000 (Europe),1-9/100000 (Netherlands),1-9/100000 (Portugal),1-9/1000000 (Germany),1-9/100000 (Turkey),1-9/100000 (Australia),1-9/1000000 (Czech Republic),1-9/1000000 (Poland),1-9/100000 (United States),1-9/100000 (Worldwide),1-9/100000 (Sweden); Age of onset: Adolescent,Adult,Childhood,Infancy; Age of death: adolescent,adult,early childhood,late childhood,young Adult;

HPO:

32
metachromatic leukodystrophy:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 54 250100
Disease Ontology 12 DOID:10581
ICD10 33 E75.25 E75.29
MeSH 42 D007966
NCIt 47 C61251
Orphanet 56 ORPHA512
ICD10 via Orphanet 34 E75.2
MESH via Orphanet 43 C538597 D007966
UMLS via Orphanet 70 C0023522 C2713319
UMLS 69 C0023522

Summaries for Metachromatic Leukodystrophy

NINDS : 51 Metachromatic leukodystrophy (MLD) is one of a group of genetic disorders called the leukodystrophies, which are characterized by the toxic buildup of lipids (fatty materials such as oils and waxes) and other storage materials in cells in the white matter of the central nervous system and peripheral nerves.  The buildup of storage materials impairs the growth or development of the myelin sheath, the fatty covering that acts as an insulator around nerve fibers. (Myelin, which lends its color to the white matter of the brain, is a complex substance made up of a mixture of fats and proteins.)  MLD is one of several lipid storage diseases, which result in the harmful buildup of lipids in brain cells and other cells and tissues in the body.  People with lipid storage diseases either do not produce enough of one of the enzymes needed to break down (metabolize) lipids or they produce enzymes that do not work properly.  Some leukodystrophies are caused by genetic defects of enzymes that regulate the metabolism of fats needed in myelin synthesis.  MLD, which affects males and females, is cause by a deficiency of the enzyme arylsulfatase A.  MLD has three characteristic forms: late infantile, juvenile, and adult. Late infantile MLD typically begins between 12 and 20 months following birth.  Infants appear normal at first but develop difficulty walking after the first year of life and eventually lose the ability to walk.  Other symptoms include muscle wasting and weakness,developmental delays, progressive loss of vision leading to blindness, impaired swallowing, and dementia before age 2. Most children with this form of MLD die by age 5. Symptoms of the juvenile formof MLD (which begins between 3-10 years of age) include impaired school performance, mental deterioration, an inability to control movements, seizures, and dementia.  Symptoms continue to get worse, and death eventually occurs 10 to  20 years following disease onset..   The adult form commonly begins after age 16, with symptoms that include psychiatric disturbances, seizures, tremor, impaired concentration, depression, and dementia.  Death generally occurs within 6 to 14 years after onset of symptoms.

MalaCards based summary : Metachromatic Leukodystrophy, also known as arylsulfatase a deficiency, is related to fucosidosis and quadriplegia, and has symptoms including ataxia, seizures and joint stiffness. An important gene associated with Metachromatic Leukodystrophy is ARSA (Arylsulfatase A), and among its related pathways/superpathways are Sphingolipid metabolism and Lysosome. The drugs Busulfan and Cyclophosphamide have been mentioned in the context of this disorder. Affiliated tissues include brain, bone and spinal cord, and related phenotypes are behavior/neurological and growth/size/body region

Disease Ontology : 12 A sphingolipidosis characterized by the accumulation of sulfatides in cells, especially the myelin producing cells of the nervous system.

Genetics Home Reference : 25 Metachromatic leukodystrophy is an inherited disorder characterized by the accumulation of fats called sulfatides in cells. This accumulation especially affects cells in the nervous system that produce myelin, the substance that insulates and protects nerves. Nerve cells covered by myelin make up a tissue called white matter. Sulfatide accumulation in myelin-producing cells causes progressive destruction of white matter (leukodystrophy) throughout the nervous system, including in the brain and spinal cord (the central nervous system) and the nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound (the peripheral nervous system).

NIH Rare Diseases : 50 metachromatic leukodystrophy is an inherited condition characterized by the accumulation of fats called sulfatides in cells, especially cells of the nervous system. this accumulation results in progressive destruction of white matter of the brain, which consists of nerve fibers covered by myelin. affected individuals experience progressive deterioration of intellectual functions and motor skills, such as the ability to walk. they also develop loss of sensation in the extremities, incontinence, seizures, paralysis, inability to speak, blindness, and hearing loss. eventually they lose awareness of their surroundings and become unresponsive. this condition is inherited in an autosomal recessive pattern and is caused by mutations in the arsa and psap genes. last updated: 9/19/2014

OMIM : 54 The metachromatic leukodystrophies comprise several allelic disorders. Kihara (1982) recognized 5 allelic forms of MLD:... (250100) more...

UniProtKB/Swiss-Prot : 66 Leukodystrophy metachromatic: A leukodystrophy due to a lysosomal storage defect. Characterized by intralysosomal storage of cerebroside-3-sulfate in neural and non- neural tissues, with a diffuse loss of myelin in the central nervous system. Progressive demyelination causes a variety of neurological symptoms, including gait disturbances, ataxias, optical atrophy, dementia, seizures, and spastic tetraparesis. Three forms of the disease can be distinguished according to the age at onset: late- infantile, juvenile and adult.

Wikipedia : 71 Metachromatic leukodystrophy (MLD, also called arylsulfatase A deficiency) is a lysosomal storage... more...

GeneReviews: NBK1130

Related Diseases for Metachromatic Leukodystrophy

Diseases in the Metachromatic Leukodystrophy family:

Metachromatic Leukodystrophy, Adult Form Metachromatic Leukodystrophy, Late Infantile Form
Metachromatic Leukodystrophy, Juvenile Form

Diseases related to Metachromatic Leukodystrophy via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 71)
id Related Disease Score Top Affiliating Genes
1 fucosidosis 30.1 HEXA MAL
2 quadriplegia 29.7 ARSB ARSH HEXA
3 mannosidosis 29.5 ARSA ARSB GALC HEXA
4 metachromatic leukodystrophy due to sap-b deficiency 12.4
5 metachromatic leukodystrophy, adult form 12.0
6 metachromatic leukodystrophy, late infantile form 12.0
7 metachromatic leukodystrophy, juvenile form 12.0
8 leukodystrophy 11.8
9 multiple sulfatase deficiency 11.6
10 sphingolipidosis 11.0
11 dementia 10.3
12 cerebritis 10.3
13 neuropathy 10.3
14 diffuse large b-cell lymphoma of the central nervous system 10.2 ARSA PSAP
15 follicular cholangitis and pancreatitis 10.2 ARSA PSAP
16 primary cutaneous anaplastic large cell lymphoma 10.2 ARSA PSAP
17 spina bifida occulta 10.2 ARSA PSAP
18 huntington disease-like 2 10.2 ARSA ARSH
19 adrenoleukodystrophy 10.2
20 serous or mucinous cystadenoma of childhood 10.2 GALC PSAP
21 krabbe disease 10.1
22 hematopoietic stem cell transplantation 10.1
23 neuronitis 10.1
24 lipid pneumonia 10.1 ARSB ARSH
25 muscle disorders 10.1 ARSH SUMF1
26 ectodermal dysplasia, hypohidrotic, with immune deficiency 10.1 ARSH SUMF1
27 leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism 10.1 ARSH PSAP
28 partial motor epilepsy 10.1 HEXA PSAP
29 hypertelorism, preauricular sinus, punctal pits, and deafness 10.1 ARSA GALC PSAP
30 neurosarcoidosis 10.1 ARSB ARSH
31 chondrodysplasia punctata, x-linked recessive 10.0 ARSH SUMF1
32 glioma susceptibility 4 10.0 ARSA HEXA PSAP
33 hypothalamic disease 10.0 ARSA HEXA PSAP
34 alzheimer disease 10.0
35 tay-sachs disease 10.0
36 schizophrenia 10.0
37 nervous system disease 10.0
38 neuronopathy, distal hereditary motor, type iic 9.9 ARSA ARSB ARSH SUMF1
39 obesity 9.9 ARSA ARSB ARSH SUMF1
40 spondyloenchondrodysplasia with immune dysregulation 9.9 HEXA PSAP
41 gaucher disease, type ii 9.9 ARSA GALC HEXA PSAP
42 dysostosis 9.9 ARSA GALC HEXA PSAP
43 mononeuritis of lower limb 9.9 ARSA GALC HEXA PSAP
44 aspartylglucosaminuria 9.8
45 early-onset familial alzheimer disease 9.8
46 conduct disorder 9.8
47 pseudoarylsulfatase a deficiency 9.8
48 ataxia 9.8
49 polyneuropathy 9.8
50 spasticity 9.8

Graphical network of the top 20 diseases related to Metachromatic Leukodystrophy:



Diseases related to Metachromatic Leukodystrophy

Symptoms & Phenotypes for Metachromatic Leukodystrophy

Symptoms by clinical synopsis from OMIM:

250100

Clinical features from OMIM:

250100

Human phenotypes related to Metachromatic Leukodystrophy:

56 32 (show all 43)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ataxia 56 32 Very frequent (99-80%) HP:0001251
2 seizures 56 32 Very frequent (99-80%) HP:0001250
3 joint stiffness 56 32 Frequent (79-30%) HP:0001387
4 muscle weakness 56 32 Very frequent (99-80%) HP:0001324
5 amaurosis fugax 56 32 Frequent (79-30%) HP:0100576
6 nystagmus 56 32 Frequent (79-30%) HP:0000639
7 intellectual disability 56 32 Very frequent (99-80%) HP:0001249
8 muscular hypotonia 56 32 Frequent (79-30%) HP:0001252
9 spasticity 56 32 Frequent (79-30%) HP:0001257
10 gait disturbance 56 32 Very frequent (99-80%) HP:0001288
11 hyperreflexia 56 32 Frequent (79-30%) HP:0001347
12 neurological speech impairment 56 32 Very frequent (99-80%) HP:0002167
13 developmental regression 56 32 Very frequent (99-80%) HP:0002376
14 behavioral abnormality 56 32 Very frequent (99-80%) HP:0000708
15 optic atrophy 56 32 Frequent (79-30%) HP:0000648
16 peripheral neuropathy 56 32 Very frequent (99-80%) HP:0009830
17 decreased nerve conduction velocity 56 32 Very frequent (99-80%) HP:0000762
18 genu recurvatum 56 32 Very frequent (99-80%) HP:0002816
19 reduced tendon reflexes 56 32 Frequent (79-30%) HP:0001315
20 aganglionic megacolon 56 32 Occasional (29-5%) HP:0002251
21 coma 56 32 Very frequent (99-80%) HP:0001259
22 dystonia 32 HP:0001332
23 emotional lability 32 HP:0000712
24 dysarthria 32 HP:0001260
25 chorea 32 HP:0002072
26 tetraplegia 32 HP:0002445
27 hallucinations 32 HP:0000738
28 spastic tetraplegia 32 HP:0002510
29 babinski sign 32 HP:0003487
30 abnormality of the musculature 56 Occasional (29-5%)
31 mental deterioration 32 HP:0001268
32 hyporeflexia 32 HP:0001265
33 cholecystitis 32 HP:0001082
34 bulbar palsy 32 HP:0001283
35 increased csf protein 32 HP:0002922
36 loss of speech 32 HP:0002371
37 urinary incontinence 32 HP:0000020
38 abnormality of the cerebral white matter 32 HP:0002500
39 progressive peripheral neuropathy 32 HP:0007133
40 gallbladder dysfunction 32 HP:0005609
41 peripheral demyelination 32 HP:0011096
42 delusions 32 HP:0000746
43 emg 32 HP:0003445

UMLS symptoms related to Metachromatic Leukodystrophy:


ataxia, seizures, muscle weakness

MGI Mouse Phenotypes related to Metachromatic Leukodystrophy:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.01 ARSA ARSB GALC HEXA PLP1 PSAP
2 growth/size/body region MP:0005378 9.91 ARSB GALC HEXA PLP1 PSAP SLC6A4
3 nervous system MP:0003631 9.81 ARSA ARSB GALC HEXA MAL PLP1
4 hearing/vestibular/ear MP:0005377 9.72 ARSA ARSB HEXA PLP1 PSAP
5 muscle MP:0005369 9.65 ARSB GALC PLP1 PSAP SLC6A4
6 skeleton MP:0005390 9.43 ARSB GALC HEXA PLP1 PSAP SUMF1
7 vision/eye MP:0005391 9.1 PSAP ARSB GALC HEXA MAL PLP1

Drugs & Therapeutics for Metachromatic Leukodystrophy

Drugs for Metachromatic Leukodystrophy (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 58)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Busulfan Approved, Investigational Phase 2, Phase 3 55-98-1 2478
2
Cyclophosphamide Approved, Investigational Phase 2, Phase 3 50-18-0, 6055-19-2 2907
3
Methylprednisolone Approved, Vet_approved Phase 2, Phase 3 83-43-2 6741
4
Prednisolone Approved, Vet_approved Phase 2, Phase 3 50-24-8 5755
5 Alkylating Agents Phase 2, Phase 3
6 Antilymphocyte Serum Phase 2, Phase 3
7 Antineoplastic Agents, Alkylating Phase 2, Phase 3
8 Antirheumatic Agents Phase 2, Phase 3
9 Immunosuppressive Agents Phase 2, Phase 3
10 Methylprednisolone acetate Phase 2, Phase 3
11 Methylprednisolone Hemisuccinate Phase 2, Phase 3
12 Prednisolone acetate Phase 2, Phase 3
13 Prednisolone hemisuccinate Phase 2, Phase 3
14 Prednisolone phosphate Phase 2, Phase 3
15
alemtuzumab Approved, Investigational Phase 2 216503-57-0
16
Benzocaine Approved Phase 2 1994-09-7, 94-09-7 2337
17
Clofarabine Approved, Investigational Phase 2 123318-82-1 119182
18
Cyclosporine Approved, Investigational, Vet_approved Phase 2 79217-60-0, 59865-13-3 5284373 6435893
19
Hydroxyurea Approved Phase 2 127-07-1 3657
20
Melphalan Approved Phase 2 148-82-3 4053 460612
21
Miconazole Approved, Investigational, Vet_approved Phase 2 22916-47-8 4189
22
Mycophenolate mofetil Approved, Investigational Phase 2 128794-94-5 5281078
23
Mycophenolic acid Approved Phase 2 24280-93-1 446541
24
Acetylcysteine Approved, Investigational Phase 2 616-91-1 12035
25
Celecoxib Approved, Investigational Phase 2 169590-42-5 2662
26
Fludarabine Approved Phase 2 21679-14-1, 75607-67-9 30751
27
rituximab Approved Phase 2 174722-31-7 10201696
28
Thiotepa Approved Phase 2 52-24-4 5453
29
Acetaminophen Approved Phase 2 103-90-2 1983
30
Diphenhydramine Approved Phase 2 58-73-1, 147-24-0 3100
31
Epinephrine Approved, Vet_approved Phase 2 51-43-4 5816
32
Promethazine Approved Phase 2 60-87-7 4927
33
Vidarabine Approved Phase 2 24356-66-9 32326 21704
34
Mesna Approved Phase 2 3375-50-6 598
35 tannic acid Approved, Nutraceutical Phase 2
36
Vitamin E Approved, Nutraceutical, Vet_approved Phase 2 59-02-9 14985
37 Antifungal Agents Phase 2
38 Anti-Infective Agents Phase 2
39 Antimetabolites Phase 2
40 Antimetabolites, Antineoplastic Phase 2
41 Calcineurin Inhibitors Phase 2
42 Dermatologic Agents Phase 2
43 Nucleic Acid Synthesis Inhibitors Phase 2
44 Anti-Bacterial Agents Phase 2
45 Antibiotics, Antitubercular Phase 2
46 N-monoacetylcystine Phase 2
47 Thioctic Acid Phase 2
48 Tocopherols Phase 2
49 Tocotrienols Phase 2
50 Vitamins Phase 2

Interventional clinical trials:

(show all 30)
id Name Status NCT ID Phase
1 Stem Cell Transplant for Inborn Errors of Metabolism Completed NCT00176904 Phase 2, Phase 3
2 ALD-101 Adjuvant Therapy of Unrelated Umbilical Cord Blood Transfusion (UCBT) in Patients With Inherited Metabolic Diseases Terminated NCT00654433 Phase 3
3 Multicenter Study of HGT-1110 Administered Intrathecally in Children With Metachromatic Leukodystrophy (MLD) Completed NCT01510028 Phase 1, Phase 2
4 Long-term Metazym Treatment of Patients With Late Infantile Metachromatic Leukodystrophy (MLD) Completed NCT00633139 Phase 1, Phase 2
5 Efficacy METAZYM for the Treatment Metachromatic Leukodystrophy Treated With Hematopoietic Stem Cell Transplantation Completed NCT01303146 Phase 2
6 HSCT for High Risk Inherited Inborn Errors Completed NCT00383448 Phase 2
7 Intracerebral Gene Therapy for Children With Early Onset Forms of Metachromatic Leukodystrophy Recruiting NCT01801709 Phase 1, Phase 2
8 Autologous Hematopoietic Stem Cell Gene Therapy for Metachromatic Leukodystrophy and Adrenoleukodystrophy Recruiting NCT02559830 Phase 1, Phase 2
9 MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis Recruiting NCT02171104 Phase 2
10 Reduced Intensity Conditioning for Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT Recruiting NCT01962415 Phase 2
11 Gene Therapy for Metachromatic Leukodystrophy Active, not recruiting NCT01560182 Phase 2
12 Phase I/II Pilot Study of Mixed Chimerism to Treat Inherited Metabolic Disorders Active, not recruiting NCT01372228 Phase 1, Phase 2
13 Allogeneic Bone Marrow Transplant for Inherited Metabolic Disorders Active, not recruiting NCT01043640 Phase 2
14 Open-Label Extension Study Evaluating Safety and Efficacy of HGT-1110 in Patients With Metachromatic Leukodystrophy Enrolling by invitation NCT01887938 Phase 1, Phase 2
15 Open-Label Extension Study of Recombinant Human Arylsulfatase A (HGT-1111) in Late Infantile MLD Terminated NCT00681811 Phase 2
16 Metazym for the Treatment of Patients With Late Infantile Metachromatic Leukodystrophy (MLD) Completed NCT00418561 Phase 1
17 UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells Recruiting NCT02254863 Phase 1
18 Human Placental-Derived Stem Cell Transplantation Recruiting NCT01586455 Phase 1
19 Fetal Umbilical Cord Blood (UCB) Transplant for Lysosomal Storage Diseases Withdrawn NCT01003912 Phase 1
20 Study of Pulmonary Complications in Pediatric Patients With Storage Disorders Undergoing Allogeneic Hematopoietic Stem Cell Transplantation Unknown status NCT00005900
21 Imaging Study of the White Matter Lesions in Children With Metachromatic Leucodystrophy Completed NCT01325025
22 Effect of Warfarin in the Treatment of Metachromatic Leukodystrophy Completed NCT00683189
23 Stem Cell Transplantation (SCT) for Genetic Diseases Completed NCT00004378
24 Reduced-Intensity Hematopoietic Stem Cell Transplant for High Risk Lysosomal and Peroxisomal Disorders Completed NCT01626092
25 Biomarker for Metachromatic Leukodystrophy Disease Recruiting NCT01536327
26 Biomarker for GM1/GM2 - Gangliosidoses Recruiting NCT02298647
27 The Natural History of Metachromatic Leukodystrophy Active, not recruiting NCT00639132
28 Allogeneic Stem Cell Transplantation for the Treatment of Multiple Sclerosis (Compassionate Use) No longer available NCT02084121
29 Single Patient Expanded Access Protocol: Metabolic Boost No longer available NCT02021266
30 Natural History Study of Children With Metachromatic Leukodystrophy Terminated NCT01963650

Search NIH Clinical Center for Metachromatic Leukodystrophy

Cell-based therapeutics:


LifeMap Discovery
Data from LifeMap, the Embryonic Development and Stem Cells Database
Read about Metachromatic Leukodystrophy cell therapies at LifeMap Discovery.

Cochrane evidence based reviews: leukodystrophy, metachromatic

Genetic Tests for Metachromatic Leukodystrophy

Genetic tests related to Metachromatic Leukodystrophy:

id Genetic test Affiliating Genes
1 Metachromatic Leukodystrophy 29
2 Arylsulfatase a Deficiency 24 ARSA

Anatomical Context for Metachromatic Leukodystrophy

MalaCards organs/tissues related to Metachromatic Leukodystrophy:

39
Brain, Bone, Spinal Cord, Bone Marrow, Skin, Liver, Eye

Publications for Metachromatic Leukodystrophy

Articles related to Metachromatic Leukodystrophy:

(show top 50) (show all 551)
id Title Authors Year
1
Quantification of plasma sulfatides by mass spectrometry: Utility for metachromatic leukodystrophy. ( 28088283 )
2017
2
Gallbladder abnormalities in children with metachromatic leukodystrophy. ( 27993207 )
2017
3
Generation of Human Induced Pluripotent Stem Cell-Derived Bona Fide Neural Stem Cells for Ex Vivo Gene Therapy of Metachromatic Leukodystrophy. ( 28191778 )
2017
4
Thickening of the peripheral nerves in metachromatic leukodystrophy. ( 27538671 )
2016
5
Metachromatic leukodystrophy: Biochemical characterization of two (p.307Glua89Lys, p.318Trpa89Cys) arylsulfatase A mutations. ( 27904824 )
2016
6
Efficacy of hematopoietic cell transplantation in metachromatic leukodystrophy: the Dutch experience. ( 27118454 )
2016
7
Classical case of late-infantile form of metachromatic leukodystrophy. ( 27365977 )
2016
8
Late-Onset Metachromatic Leukodystrophy with Early Onset Dementia Associated with a Novel Missense Mutation in the Arylsulfatase A Gene. ( 26890752 )
2016
9
Whole-exome sequencing identifies compound heterozygous mutations in ARSA of two siblings presented with atypical onset of metachromatic leukodystrophy from a Chinese pedigree. ( 27374302 )
2016
10
Sulfatide Analysis by Mass Spectrometry for Screening of Metachromatic Leukodystrophy in Dried Blood and Urine Samples. ( 26585924 )
2016
11
Lentiviral haemopoietic stem-cell gene therapy in early-onset metachromatic leukodystrophy: an ad-hoc analysis of a non-randomised, open-label, phase 1/2 trial. ( 27289174 )
2016
12
Metachromatic Leukodystrophy: An Assessment of Disease Burden. ( 27389394 )
2016
13
Long-term Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Juvenile Metachromatic Leukodystrophy Compared With Nontransplanted Control Patients. ( 27400410 )
2016
14
Immunostaining of Sulfatide-Storing Macrophages in Gallbladder of a Patient With Metachromatic Leukodystrophy. ( 27640320 )
2016
15
Generation of Human Induced Pluripotent Stem Cell-Derived Bona Fide Neural Stem Cells for Ex Vivo Gene Therapy of Metachromatic Leukodystrophy. ( 27638920 )
2016
16
Cerebral Spinal Fluid levels of Cytokines are elevated in Patients with Metachromatic Leukodystrophy. ( 27079147 )
2016
17
Infantile metachromatic leukodystrophy in an 18 month old girl. ( 27654749 )
2016
18
Gallbladder and the risk of polyps and carcinoma in metachromatic leukodystrophy. ( 27261095 )
2016
19
Neurological outcomes after hematopoietic stem cell transplantation for cerebral X-linked adrenoleukodystrophy, late onset metachromatic leukodystrophy and Hurler syndrome. ( 27991992 )
2016
20
Diffusion-weighted magnetic resonance imaging findings in a case of metachromatic leukodystrophy. ( 27606023 )
2016
21
Gene therapy for metachromatic leukodystrophy. ( 27638601 )
2016
22
Acetobacter indonesiensis Bacteremia in Child with Metachromatic Leukodystrophy. ( 27533630 )
2016
23
Long-term outcomes after allogeneic hematopoietic stem cell transplantation for metachromatic leukodystrophy: the largest single-institution cohort report. ( 26245762 )
2015
24
Late infantile metachromatic leukodystrophy: Clinical manifestations of five Taiwanese patients and Genetic features in Asia. ( 26553228 )
2015
25
Genotypic characterization of Brazilian patients with infantile and juvenile forms of metachromatic leukodystrophy. ( 25965562 )
2015
26
Abnormalities of acid-base balance and predisposition to metabolic acidosis in Metachromatic Leukodystrophy patients. ( 25796965 )
2015
27
Arylsulfatase A Overexpressing Human iPSC-derived Neural Cells Reduce CNS Sulfatide Storage in a Mouse Model of Metachromatic Leukodystrophy. ( 26061647 )
2015
28
Mutation Update of ARSA and PSAP Genes Causing Metachromatic Leukodystrophy. ( 26462614 )
2015
29
The clinical features and diagnosis of Metachromatic leukodystrophy: A case series of Iranian Pediatric Patients. ( 26401154 )
2015
30
Multidetector CT diagnosis of massive hemobilia due to gallbladder polyposis in a child with metachromatic leukodystrophy. ( 26160127 )
2015
31
Sulfatide levels correlate with severity of neuropathy in metachromatic leukodystrophy. ( 26000324 )
2015
32
Pathology of the Gallbladder in a Child with Metachromatic Leukodystrophy. ( 25569213 )
2015
33
Biochemical and Genetic Analysis of Seven Korean Individuals With Suspected Metachromatic Leukodystrophy. ( 26131420 )
2015
34
Enzyme replacement in the CSF to treat metachromatic leukodystrophy in mouse model using single intracerebroventricular injection of self-complementary AAV1 vector. ( 26283284 )
2015
35
Anti-inflammatory therapy with simvastatin improves neuroinflammation and CNS function in a mouse model of metachromatic leukodystrophy. ( 25896249 )
2015
36
Volumetric MRI data correlate to disease severity in metachromatic leukodystrophy. ( 26401514 )
2015
37
Outcome of Early Juvenile Onset Metachromatic Leukodystrophy After Unrelated Cord Blood Transplantation: A Case Series and Review of the Literature. ( 26187619 )
2015
38
Metachromatic leukodystrophy: Disease spectrum and approaches for treatment. ( 25987178 )
2015
39
Intracerebral gene therapy using AAVrh.10-hARSA recombinant vector to treat patients with early-onset forms of metachromatic leukodystrophy: preclinical feasibility and safety assessments in non-human primates. ( 25758611 )
2015
40
A Rare Case of Metachromatic Leukodystrophy Confirmed by Arylsulfatase A. ( 26620033 )
2015
41
Lentivector integration sites in ependymal cells from a model of metachromatic leukodystrophy: non-B DNA as a new factor influencing integration. ( 25158091 )
2014
42
A 5-Year-Old Male Child With Late Infantile Metachromatic Leukodystrophy: A Case Report. ( 25117420 )
2014
43
A new analytical bench assay for the determination of arylsulfatase a activity toward galactosyl-3-sulfate ceramide: implication for metachromatic leukodystrophy diagnosis. ( 24294900 )
2014
44
The Complementary Role of the Kinect Virtual Reality Game Training in a Patient With Metachromatic Leukodystrophy. ( 24412636 )
2014
45
Metachromatic leukodystrophy presenting as bipolar disorder. ( 25237139 )
2014
46
A novel homozygous splicing mutation in PSAP gene causes metachromatic leukodystrophy in two Moroccan brothers. ( 24478108 )
2014
47
Kidney transplantation from a deceased donor with metachromatic leukodystrophy. ( 24686430 )
2014
48
Ultra-performance liquid chromatography/tandem mass spectrometry for determination of sulfatides in dried blood spots from patients with metachromatic leukodystrophy. ( 24519821 )
2014
49
[Analysis of phenotype and genotype in a family with late infantile metachromatic leukodystrophy]. ( 25297594 )
2014
50
Hematopoietic SCT: a useful treatment for late metachromatic leukodystrophy. ( 24797185 )
2014

Variations for Metachromatic Leukodystrophy

UniProtKB/Swiss-Prot genetic disease variations for Metachromatic Leukodystrophy:

66 (show top 50) (show all 97)
id Symbol AA change Variation ID SNP ID
1 ARSA p.Pro82Leu VAR_007244 rs6151411
2 ARSA p.Arg84Gln VAR_007245 rs74315458
3 ARSA p.Gly86Asp VAR_007246 rs74315460
4 ARSA p.Ser95Asn VAR_007247 rs199476363
5 ARSA p.Ser96Phe VAR_007248 rs74315456
6 ARSA p.Ser96Leu VAR_007249 rs199476371
7 ARSA p.Gly99Asp VAR_007250 rs74315455
8 ARSA p.Gly119Arg VAR_007251 rs199476364
9 ARSA p.Gly122Ser VAR_007252 rs74315461
10 ARSA p.Leu135Pro VAR_007253 rs121434215
11 ARSA p.Pro136Leu VAR_007254 rs74315462
12 ARSA p.Asp152Tyr VAR_007255 rs199476365
13 ARSA p.Gly154Asp VAR_007256 rs74315463
14 ARSA p.Pro155Arg VAR_007257 rs74315464
15 ARSA p.Pro167Arg VAR_007258 rs74315465
16 ARSA p.Asp169Asn VAR_007259 rs74315466
17 ARSA p.Cys172Tyr VAR_007260 rs199476381
18 ARSA p.Ile179Ser VAR_007261 rs74315457
19 ARSA p.Tyr201Cys VAR_007263 rs199476345
20 ARSA p.Ala212Val VAR_007264 rs74315467
21 ARSA p.Ala224Val VAR_007265 rs74315468
22 ARSA p.Pro231Thr VAR_007266 rs74315469
23 ARSA p.Arg244Cys VAR_007267 rs74315470
24 ARSA p.Arg244His VAR_007268 rs199476366
25 ARSA p.Gly245Arg VAR_007269 rs74315471
26 ARSA p.Ser250Tyr VAR_007270 rs199476367
27 ARSA p.Thr274Met VAR_007271 rs74315472
28 ARSA p.Arg288Cys VAR_007272 rs74315473
29 ARSA p.Ser295Tyr VAR_007273 rs74315474
30 ARSA p.Gly309Ser VAR_007274 rs74315459
31 ARSA p.Arg311Gln VAR_007275 rs199476382
32 ARSA p.Ala314Thr VAR_007276 rs199476368
33 ARSA p.Asp335Val VAR_007277 rs74315475
34 ARSA p.Lys367Asn VAR_007279 rs199476369
35 ARSA p.Arg370Gln VAR_007280 rs74315477
36 ARSA p.Arg370Trp VAR_007281 rs74315476
37 ARSA p.Pro377Leu VAR_007282 rs74315478
38 ARSA p.Glu382Lys VAR_007283 rs74315479
39 ARSA p.Arg384Cys VAR_007284 rs199476370
40 ARSA p.Arg390Gln VAR_007285 rs199476391
41 ARSA p.Arg390Trp VAR_007286 rs74315480
42 ARSA p.His397Tyr VAR_007288 rs199476376
43 ARSA p.Pro426Leu VAR_007291 rs28940893
44 ARSA p.Cys300Phe VAR_008132 rs74315484
45 ARSA p.Pro425Thr VAR_008133 rs74315485
46 ARSA p.Ala18Asp VAR_054164 rs199476339
47 ARSA p.Asp29Asn VAR_054165 rs199476346
48 ARSA p.Asp30His VAR_054166 rs199476340
49 ARSA p.Gly32Ser VAR_054167 rs199476350
50 ARSA p.Leu68Pro VAR_054168 rs199476351

ClinVar genetic disease variations for Metachromatic Leukodystrophy:

6 (show top 50) (show all 67)
id Gene Variation Type Significance SNP ID Assembly Location
1 ARSA NM_000487.5(ARSA): c.465+1G> A single nucleotide variant Pathogenic rs80338815 GRCh37 Chromosome 22, 51065593: 51065593
2 ARSA NM_000487.5(ARSA): c.1283C> T (p.Pro428Leu) single nucleotide variant Pathogenic rs28940893 GRCh37 Chromosome 22, 51063820: 51063820
3 ARSA NM_000487.5(ARSA): c.293C> T (p.Ser98Phe) single nucleotide variant Pathogenic/Likely pathogenic rs74315456 GRCh37 Chromosome 22, 51065766: 51065766
4 ARSA ARSA, 11-BP DEL, EX8 deletion Pathogenic
5 ARSA ARSA, 1-BP DEL, 447C deletion Pathogenic
6 ARSA NM_000487.5(ARSA): c.542T> G (p.Ile181Ser) single nucleotide variant Pathogenic rs74315457 GRCh37 Chromosome 22, 51065404: 51065404
7 ARSA NM_000487.5(ARSA): c.1210+1G> A single nucleotide variant Pathogenic rs80338820 GRCh37 Chromosome 22, 51064006: 51064006
8 ARSA NM_000487.5(ARSA): c.931G> A (p.Gly311Ser) single nucleotide variant Pathogenic rs74315459 GRCh37 Chromosome 22, 51064630: 51064630
9 ARSA ARSA, 1-BP DEL, 297C deletion Pathogenic
10 ARSA NM_000487.5(ARSA): c.467G> A (p.Gly156Asp) single nucleotide variant Pathogenic rs74315463 GRCh37 Chromosome 22, 51065479: 51065479
11 ARSA NM_000487.5(ARSA): c.506C> G (p.Pro169Arg) single nucleotide variant Pathogenic rs74315465 GRCh37 Chromosome 22, 51065440: 51065440
12 ARSA NM_000487.5(ARSA): c.641C> T (p.Ala214Val) single nucleotide variant Pathogenic rs74315467 GRCh37 Chromosome 22, 51065305: 51065305
13 ARSA NM_000487.5(ARSA): c.697C> A (p.Pro233Thr) single nucleotide variant Pathogenic rs74315469 GRCh37 Chromosome 22, 51065176: 51065176
14 ARSA NM_000487.5(ARSA): c.736C> T (p.Arg246Cys) single nucleotide variant Pathogenic/Likely pathogenic rs74315470 GRCh37 Chromosome 22, 51065137: 51065137
15 ARSA NM_000487.5(ARSA): c.739G> A (p.Gly247Arg) single nucleotide variant Pathogenic rs74315471 GRCh37 Chromosome 22, 51065134: 51065134
16 ARSA NM_000487.5(ARSA): c.827C> T (p.Thr276Met) single nucleotide variant Pathogenic/Likely pathogenic rs74315472 GRCh37 Chromosome 22, 51065046: 51065046
17 ARSA NM_000487.5(ARSA): c.868C> T (p.Arg290Cys) single nucleotide variant Pathogenic/Likely pathogenic rs74315473 GRCh37 Chromosome 22, 51064693: 51064693
18 ARSA NM_000487.5(ARSA): c.1010A> T (p.Asp337Val) single nucleotide variant Pathogenic/Likely pathogenic rs74315475 GRCh37 Chromosome 22, 51064461: 51064461
19 ARSA NM_000487.5(ARSA): c.1114C> T (p.Arg372Trp) single nucleotide variant Pathogenic/Likely pathogenic rs74315476 GRCh37 Chromosome 22, 51064103: 51064103
20 ARSA NM_000487.5(ARSA): c.1150G> A (p.Glu384Lys) single nucleotide variant Pathogenic rs74315479 GRCh37 Chromosome 22, 51064067: 51064067
21 ARSA ARSA, 3-BP DEL, PHE398DEL deletion Pathogenic
22 ARSA NM_000487.5(ARSA): c.1232C> T (p.Thr411Ile) single nucleotide variant Pathogenic rs74315481 GRCh37 Chromosome 22, 51063871: 51063871
23 ARSA NM_000487.5(ARSA): c.410T> C (p.Leu137Pro) single nucleotide variant Pathogenic rs121434215 GRCh37 Chromosome 22, 51065649: 51065649
24 ARSA NM_000487.5(ARSA): c.862A> C (p.Thr288Pro) single nucleotide variant Pathogenic rs28940894 GRCh37 Chromosome 22, 51064699: 51064699
25 ARSA NM_000487.5(ARSA): c.763G> A (p.Glu255Lys) single nucleotide variant Pathogenic/Likely pathogenic rs74315483 GRCh37 Chromosome 22, 51065110: 51065110
26 ARSA NM_000487.5(ARSA): c.1229C> T (p.Thr410Ile) single nucleotide variant Pathogenic rs28940895 GRCh37 Chromosome 22, 51063874: 51063874
27 ARSA NM_000487.5(ARSA): c.905G> T (p.Cys302Phe) single nucleotide variant Pathogenic rs74315484 GRCh37 Chromosome 22, 51064656: 51064656
28 ARSA NM_000487.5(ARSA): c.1279C> A (p.Pro427Thr) single nucleotide variant Pathogenic rs74315485 GRCh37 Chromosome 22, 51063824: 51063824
29 ARSA NM_000487.5(ARSA): c.257G> A (p.Arg86Gln) single nucleotide variant Pathogenic rs74315458 GRCh37 Chromosome 22, 51065802: 51065802
30 ARSA NM_000487.5(ARSA): c.769G> C (p.Asp257His) single nucleotide variant Pathogenic rs80338819 GRCh37 Chromosome 22, 51065104: 51065104
31 ARSA NM_000487.5(ARSA): c.1175G> A (p.Arg392Gln) single nucleotide variant Likely pathogenic rs199476391 GRCh37 Chromosome 22, 51064042: 51064042
32 ARSA NM_000487.5(ARSA): c.256C> T (p.Arg86Trp) single nucleotide variant Pathogenic rs199476352 GRCh37 Chromosome 22, 51065803: 51065803
33 ARSA NM_000487.5(ARSA): c.737G> A (p.Arg246His) single nucleotide variant Pathogenic rs199476366 GRCh37 Chromosome 22, 51065136: 51065136
34 ARSA NM_000487.5(ARSA): c.883G> A (p.Gly295Ser) single nucleotide variant Pathogenic/Likely pathogenic rs199476349 GRCh37 Chromosome 22, 51064678: 51064678
35 ARSA NM_000487.5(ARSA): c.899T> C (p.Leu300Ser) single nucleotide variant Pathogenic rs199476389 GRCh37 Chromosome 22, 51064662: 51064662
36 ARSA NM_000487.5(ARSA): c.1108-2A> G single nucleotide variant Pathogenic rs398123411 GRCh37 Chromosome 22, 51064111: 51064111
37 ARSA NM_000487.5(ARSA): c.1125_1126delCT (p.Phe376Leufs) deletion Pathogenic rs398123412 GRCh37 Chromosome 22, 51064091: 51064092
38 ARSA NM_000487.5(ARSA): c.195delC (p.Tyr65Terfs) deletion Pathogenic rs398123414 GRCh37 Chromosome 22, 51066013: 51066013
39 ARSA NM_000487.5(ARSA): c.34delG (p.Ala12Profs) deletion Pathogenic rs398123415 GRCh37 Chromosome 22, 51066174: 51066174
40 ARSA NM_000487.5(ARSA): c.583delT (p.Trp195Glyfs) deletion Pathogenic rs398123416 GRCh37 Chromosome 22, 51065363: 51065363
41 ARSA NM_000487.5(ARSA): c.986C> T (p.Thr329Ile) single nucleotide variant Pathogenic rs398123418 GRCh37 Chromosome 22, 51064485: 51064485
42 ARSA NM_000487.5(ARSA): c.991G> T (p.Glu331Ter) single nucleotide variant Pathogenic rs398123419 GRCh37 Chromosome 22, 51064480: 51064480
43 ARSA NM_000487.5(ARSA): c.1489_1492dupCCCC (p.Arg498Profs) duplication Likely pathogenic rs774153480 GRCh38 Chromosome 22, 50625183: 50625186
44 ARSA NM_000487.5(ARSA): c.1223_1231delGTGATACCA (p.Ser408_Thr410del) deletion Likely pathogenic rs765905826 GRCh37 Chromosome 22, 51063872: 51063880
45 ARSA NM_000487.5(ARSA): c.979+1G> A single nucleotide variant Likely pathogenic rs754722529 GRCh37 Chromosome 22, 51064581: 51064581
46 ARSA NM_000487.5(ARSA): c.304delC (p.Leu102Cysfs) deletion Likely pathogenic rs786204673 GRCh37 Chromosome 22, 51065755: 51065755
47 ARSA NM_000487.5(ARSA): c.240dupC (p.Gly81Argfs) duplication Likely pathogenic rs786204599 GRCh38 Chromosome 22, 50627391: 50627391
48 ARSA NM_000487.5(ARSA): c.1408_1418delGCAGCTGTGAC (p.Ala470Leufs) deletion Pathogenic rs80338823 GRCh37 Chromosome 22, 51063685: 51063695
49 ARSA NM_000487.5(ARSA): c.346C> T (p.Arg116Ter) single nucleotide variant Pathogenic rs761860059 GRCh37 Chromosome 22, 51065713: 51065713
50 ARSA NM_000487.5(ARSA): c.674_675dupAT (p.Ala226Metfs) duplication Likely pathogenic rs1057516373 GRCh38 Chromosome 22, 50626843: 50626844

Copy number variations for Metachromatic Leukodystrophy from CNVD:

7
id CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1 160376 22 14700000 51304566 Copy number ARSA Metachromatic leukodystrophy

Expression for Metachromatic Leukodystrophy

Search GEO for disease gene expression data for Metachromatic Leukodystrophy.

Pathways for Metachromatic Leukodystrophy

GO Terms for Metachromatic Leukodystrophy

Cellular components related to Metachromatic Leukodystrophy according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 endoplasmic reticulum lumen GO:0005788 9.46 ARSA ARSB ARSH SUMF1
2 lysosome GO:0005764 9.35 ARSA ARSB GALC HEXA PSAP
3 lysosomal lumen GO:0043202 9.02 ARSA ARSB GALC HEXA PSAP

Biological processes related to Metachromatic Leukodystrophy according to GeneCards Suite gene sharing:

(show all 12)
id Name GO ID Score Top Affiliating Genes
1 post-translational protein modification GO:0043687 9.62 ARSA ARSB ARSH SUMF1
2 central nervous system development GO:0007417 9.61 ARSA ARSB MAL
3 response to estrogen GO:0043627 9.51 ARSA ARSB
4 myelination GO:0042552 9.49 MAL PLP1
5 cellular response to organic substance GO:0071310 9.48 PSAP SLC6A4
6 sphingolipid metabolic process GO:0006665 9.46 GALC PSAP
7 response to nutrient GO:0007584 9.43 ARSA ARSB SLC6A4
8 chondroitin sulfate catabolic process GO:0030207 9.4 ARSB HEXA
9 response to pH GO:0009268 9.37 ARSA ARSB
10 metabolic process GO:0008152 9.35 ARSA ARSB ARSH GALC HEXA
11 glycosphingolipid metabolic process GO:0006687 9.17 ARSA ARSB ARSH GALC HEXA PSAP
12 response to methylmercury GO:0051597 9.16 ARSA ARSB

Molecular functions related to Metachromatic Leukodystrophy according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 hydrolase activity GO:0016787 9.65 ARSA ARSB ARSH GALC HEXA
2 structural constituent of myelin sheath GO:0019911 9.16 MAL PLP1
3 sulfuric ester hydrolase activity GO:0008484 9.13 ARSA ARSB ARSH
4 arylsulfatase activity GO:0004065 8.8 ARSA ARSB ARSH

Sources for Metachromatic Leukodystrophy

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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