MLD
MCID: MTC003
MIFTS: 70

Metachromatic Leukodystrophy (MLD)

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

Aliases & Classifications for Metachromatic Leukodystrophy

MalaCards integrated aliases for Metachromatic Leukodystrophy:

Name: Metachromatic Leukodystrophy 56 12 24 52 25 53 58 73 36 29 13 6 15 37
Arylsulfatase a Deficiency 56 12 74 24 52 58 73 71
Mld 56 12 52 25 58 73
Arsa Deficiency 56 24 52 25 73
Leukodystrophy, Metachromatic 74 43 39 71
Sulfatide Lipidosis 56 52 25 73
Cerebral Sclerosis, Diffuse, Metachromatic Form 56 25 73
Metachromatic Leukoencephalopathy 56 52 25
Cerebroside Sulfatase Deficiency 56 52 73
Pseudoarylsulfatase a Deficiency 73 6 71
Metachromatic Leukodystrophy, Late Infantile 73 6
Metachromatic Leukodystrophy Variant 6 71
Leukodystrophy Metachromatic 52 54
Sulfatidosis 25 71
Cerebral Sclerosis Diffuse Metachromatic Form 52
Leukodystrophy Metachromatic Late Infantile 54
Metachromatic Leukodystrophy, Juvenile Type 6
Cerebroside Sulphatase Deficiency Disease 25
Metachromatic Leukodystrophy, Adult Type 6
Metachromatic Leukodystrophy, Juvenile 73
Leukodystrophy Metachromatic Juvenile 54
Metachromatic Leukodystrophy, Infant 71
Deficiency of Cerebroside-Sulfatase 12
Metachromatic Leukodystrophy, Adult 73
Arylsulfatase a Deficiency Disease 25
Leukodystrophy Metachromatic Adult 54
Scholz Cerebral Sclerosis 12
Sulfatide Lipoidosis 12
Greenfield Disease 25

Characteristics:

Orphanet epidemiological data:

58
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;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
late infantile onset 6-24 months
juvenile onset 4 years to puberty
adult onset after puberty
adult onset form usually presents with psychiatric manifestations
pseudoarylsulfatase a deficiency is an allelic disorder with reduced levels of arsa activity, but no neurologic manifestations


HPO:

31
metachromatic leukodystrophy:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Inborn errors of metabolism


Summaries for Metachromatic Leukodystrophy

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). In people with metachromatic leukodystrophy, white matter damage causes progressive deterioration of intellectual functions and motor skills, such as the ability to walk. Affected individuals also develop loss of sensation in the extremities (peripheral neuropathy), incontinence, seizures, paralysis, an inability to speak, blindness, and hearing loss. Eventually they lose awareness of their surroundings and become unresponsive. While neurological problems are the primary feature of metachromatic leukodystrophy, effects of sulfatide accumulation on other organs and tissues have been reported, most often involving the gallbladder. The most common form of metachromatic leukodystrophy, affecting about 50 to 60 percent of all individuals with this disorder, is called the late infantile form. This form of the disorder usually appears in the second year of life. Affected children lose any speech they have developed, become weak, and develop problems with walking (gait disturbance). As the disorder worsens, muscle tone generally first decreases, and then increases to the point of rigidity. Individuals with the late infantile form of metachromatic leukodystrophy typically do not survive past childhood. In 20 to 30 percent of individuals with metachromatic leukodystrophy, onset occurs between the age of 4 and adolescence. In this juvenile form, the first signs of the disorder may be behavioral problems and increasing difficulty with schoolwork. Progression of the disorder is slower than in the late infantile form, and affected individuals may survive for about 20 years after diagnosis. The adult form of metachromatic leukodystrophy affects approximately 15 to 20 percent of individuals with the disorder. In this form, the first symptoms appear during the teenage years or later. Often behavioral problems such as alcoholism, drug abuse, or difficulties at school or work are the first symptoms to appear. The affected individual may experience psychiatric symptoms such as delusions or hallucinations. People with the adult form of metachromatic leukodystrophy may survive for 20 to 30 years after diagnosis. During this time there may be some periods of relative stability and other periods of more rapid decline. Metachromatic leukodystrophy gets its name from the way cells with an accumulation of sulfatides appear when viewed under a microscope. The sulfatides form granules that are described as metachromatic, which means they pick up color differently than surrounding cellular material when stained for examination.

MalaCards based summary : Metachromatic Leukodystrophy, also known as arylsulfatase a deficiency, is related to metachromatic leukodystrophy, late infantile form and metachromatic leukodystrophy, juvenile form, and has symptoms including seizures, muscle weakness and ataxia. 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 bone marrow, and related phenotypes are behavioral abnormality and developmental regression

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

NIH Rare Diseases : 52 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 .

OMIM : 56 The metachromatic leukodystrophies comprise several allelic disorders. Kihara (1982) recognized 5 allelic forms of MLD: late infantile, juvenile, and adult forms, partial cerebroside sulfate deficiency, and pseudoarylsulfatase A deficiency; and 2 nonallelic forms: metachromatic leukodystrophy due to saposin B deficiency (249900) and multiple sulfatase deficiency or juvenile sulfatidosis (272200), a disorder that combines features of a mucopolysaccharidosis with those of metachromatic leukodystrophy. (250100)

NINDS : 53 Metachromatic leukodystrophy (MLD) is one of a group of genetic disorders 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. MLD, which affects males and females, is cause by a deficiency of the enzyme arylsulfatase A.   MLD has three characteristic forms: 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. Juvenile formof MLD (which begins between 3-10 years of age) includes 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..    Adult MLD 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.

KEGG : 36 Metachromatic leukodystrophy (MLD) is an autosomal recessive demyelinating lysosomal storage disease caused by deficiency of lysosomal arylsulfatase A (ARSA). The enzyme defect results in the accumulation of sulfatide in the central and peripheral nervous systems and extensive white matter damage and loss of both cognitive and motor functions. Mutated PSAP gene resulting in sphingolipid activator protein B deficiency is known to cause MLD variant in which ARSA is normal.

UniProtKB/Swiss-Prot : 73 Metachromatic leukodystrophy: An autosomal recessive disease caused by abnormal intralysosomal accumulation of cerebroside-3-sulfate in central and peripheral nervous systems, as well as other organs. MLD is clinically characterized by leukodystrophy, progressive demyelination and a variety of neurological symptoms, including gait disturbances, ataxias, optical atrophy, dementia, seizures, and spastic tetraparesis. Decreased arylsulfatase A activity is detected in urine, leukocytes, and fibroblasts of affected individuals. Several forms of the disease can be distinguished according to the age at onset and disease severity: late infantile, juvenile and adult forms, partial cerebroside sulfate deficiency, and pseudoarylsulfatase A deficiency. Individuals with pseudoarylsulfatase A deficiency have low arylsulfatase A activity but lack neurological manifestations and are apparently healthy.

Wikipedia : 74 Metachromatic leukodystrophy (MLD) is a lysosomal storage disease which is commonly listed in the family... 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 200)
# Related Disease Score Top Affiliating Genes
1 metachromatic leukodystrophy, late infantile form 34.7 PSAP ARSA
2 metachromatic leukodystrophy, juvenile form 34.6 PSAP ARSA
3 metachromatic leukodystrophy, adult form 34.5 PSAP ARSA
4 multiple sulfatase deficiency 33.9 SUMF1 STS ARSH ARSB ARSA
5 sphingolipidosis 33.3 PSAP IDUA HEXA GLA GALC ARSH
6 leukodystrophy 33.2 UGT8 SUMF1 SLC6A3 SCP2 PSAP PLP1
7 lysosomal storage disease 32.0 SUMF1 PSAP IDUA HEXA GLA GALC
8 krabbe disease 31.7 PSAP PLP1 IDUA GLA GALC CDH23
9 demyelinating disease 31.7 PLP1 MPZ GALC ARSA
10 hurler syndrome 31.6 IDUA ARSH ARSB
11 gangliosidosis 31.4 PSAP HEXA
12 gaucher disease, type i 31.2 PSAP IDUA HEXA GLA GALC ARSH
13 tay-sachs disease 31.2 PSAP IDUA HEXA GLA ARSH ARSA
14 lipid storage disease 31.2 PSAP GLA GALC ARSA
15 fabry disease 31.1 PSAP GLA ARSA
16 infantile krabbe disease 31.1 PSAP GALC
17 scheie syndrome 31.1 SUMF1 IDUA GLA ARSH ARSB ARSA
18 mucopolysaccharidoses 31.1 IDUA ARSH ARSB
19 dystonia 31.1 STS SLC6A3 SCP2 PLP1 GALC ARSA
20 combined saposin deficiency 31.1 PSAP GALC CDH23 ARSA
21 mucopolysaccharidosis-plus syndrome 31.1 SUMF1 IDUA HEXA GLA GALC ARSH
22 gaucher disease, atypical, due to saposin c deficiency 31.1 PSAP CDH23
23 aspartylglucosaminuria 31.1 PSAP IDUA ARSA
24 hydrocephalus 30.9 SUMF1 SLC6A3 ARSH ARSB ARSA
25 gm1 gangliosidosis 30.9 PSAP IDUA GLA GALC ARSH ARSA
26 ichthyosis 30.9 SUMF1 STS ERCC2 ARSH ARSB ARSA
27 hereditary neuropathies 30.8 PLP1 MPZ
28 ichthyosis, x-linked 30.7 SUMF1 STS ARSH
29 farber lipogranulomatosis 30.6 PSAP GALC
30 metachromatic leukodystrophy due to saposin b deficiency 13.0
31 metachromatic leukodystrophy, adult-onset, with normal arylsulfatase a 12.6
32 autosomal recessive disease 10.8
33 neuropathy 10.7
34 peripheral nervous system disease 10.7
35 papilloma 10.6
36 krabbe disease, atypical, due to saposin a deficiency 10.6 PSAP CDH23
37 retinitis pigmentosa-deafness syndrome 10.6 PSAP CDH23
38 polyneuropathy 10.6
39 mucopolysaccharidosis, type ivb 10.6 IDUA ARSH ARSB
40 mucopolysaccharidosis, type iiic 10.6 IDUA ARSH ARSB
41 niemann-pick disease 10.6 UGT8 PSAP PLP1
42 galactosialidosis 10.6 PSAP IDUA ARSH
43 mucopolysaccharidosis, type vii 10.6 IDUA ARSH ARSB ARSA
44 mucopolysaccharidosis, type iiid 10.6 SUMF1 IDUA ARSH ARSB
45 mucopolysaccharidosis, type iiib 10.6 SUMF1 IDUA ARSH ARSB
46 ataxia and polyneuropathy, adult-onset 10.6
47 adrenomyeloneuropathy 10.6
48 x-linked chondrodysplasia punctata 1 10.6 SUMF1 ARSA
49 mucopolysaccharidosis, type iiia 10.6 SUMF1 IDUA ARSH ARSB ARSA
50 gm1-gangliosidosis, type i 10.6 PSAP HEXA GLA ARSA

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



Diseases related to Metachromatic Leukodystrophy

Symptoms & Phenotypes for Metachromatic Leukodystrophy

Human phenotypes related to Metachromatic Leukodystrophy:

58 31 (show top 50) (show all 75)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 behavioral abnormality 58 31 hallmark (90%) Occasional (29-5%) HP:0000708
2 developmental regression 58 31 hallmark (90%) Frequent (79-30%) HP:0002376
3 muscle weakness 58 31 hallmark (90%) Frequent (79-30%) HP:0001324
4 gait disturbance 58 31 hallmark (90%) Frequent (79-30%) HP:0001288
5 ataxia 58 31 hallmark (90%) Frequent (79-30%) HP:0001251
6 peripheral neuropathy 58 31 hallmark (90%) Frequent (79-30%) HP:0009830
7 decreased nerve conduction velocity 58 31 hallmark (90%) Frequent (79-30%) HP:0000762
8 intellectual disability 31 hallmark (90%) HP:0001249
9 neurological speech impairment 31 hallmark (90%) HP:0002167
10 genu recurvatum 31 hallmark (90%) HP:0002816
11 coma 31 hallmark (90%) HP:0001259
12 seizure 31 hallmark (90%) HP:0001250
13 muscular hypotonia 31 frequent (33%) HP:0001252
14 joint stiffness 31 frequent (33%) HP:0001387
15 optic atrophy 31 frequent (33%) HP:0000648
16 spasticity 31 frequent (33%) HP:0001257
17 nystagmus 31 frequent (33%) HP:0000639
18 hyperreflexia 31 frequent (33%) HP:0001347
19 reduced tendon reflexes 31 frequent (33%) HP:0001315
20 amaurosis fugax 31 frequent (33%) HP:0100576
21 aganglionic megacolon 31 occasional (7.5%) HP:0002251
22 dysarthria 58 31 Occasional (29-5%) HP:0001260
23 dystonia 58 31 Occasional (29-5%) HP:0001332
24 hyporeflexia 58 31 Frequent (79-30%) HP:0001265
25 emotional lability 58 31 Occasional (29-5%) HP:0000712
26 urinary incontinence 58 31 Occasional (29-5%) HP:0000020
27 increased csf protein 58 31 Frequent (79-30%) HP:0002922
28 hearing impairment 58 Frequent (79-30%)
29 hallucinations 31 HP:0000738
30 seizures 58 Frequent (79-30%)
31 visual impairment 58 Frequent (79-30%)
32 abnormality of visual evoked potentials 58 Frequent (79-30%)
33 spastic tetraplegia 31 HP:0002510
34 feeding difficulties 58 Occasional (29-5%)
35 tremor 58 Occasional (29-5%)
36 abnormality of the stomach 58 Very rare (<4-1%)
37 bowel incontinence 58 Occasional (29-5%)
38 toe walking 58 Occasional (29-5%)
39 schizophrenia 58 Occasional (29-5%)
40 mental deterioration 31 HP:0001268
41 chorea 31 HP:0002072
42 psychosis 58 Occasional (29-5%)
43 progressive spasticity 58 Frequent (79-30%)
44 cholecystitis 31 HP:0001082
45 babinski sign 31 HP:0003487
46 dementia 58 Occasional (29-5%)
47 abnormality of the cerebral white matter 31 HP:0002500
48 decerebrate rigidity 58 Very rare (<4-1%)
49 gastrostomy tube feeding in infancy 58 Occasional (29-5%)
50 generalized hypotonia 31 HP:0001290

Symptoms via clinical synopsis from OMIM:

56
Neurologic Behavioral Psychiatric Manifestations:
hallucinations
emotional lability
delusions
behavioral disturbances
poor school performance
more
Head And Neck Eyes:
optic atrophy

Genitourinary Bladder:
urinary incontinence

Neurologic Peripheral Nervous System:
delayed nerve conduction velocity
demyelination
progressive polyneuropathy
emg shows neuropathic changes

Neurologic Central Nervous System:
seizures
muscle weakness
spastic tetraplegia
ataxia
dysarthria
more
Abdomen Biliary Tract:
cholecystitis
gallbladder dysfunction

Laboratory Abnormalities:
increased csf protein
metachromatic deposits (sulfatide-containing) in central and peripheral nervous systems and visceral organs
decreased arylsulfatase a (arsa) activity in urine, leukocytes, fibroblasts
increased urinary sulfatide excretion

Clinical features from OMIM:

250100

UMLS symptoms related to Metachromatic Leukodystrophy:


seizures, muscle weakness, ataxia

MGI Mouse Phenotypes related to Metachromatic Leukodystrophy:

45 (show all 16)
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.46 ARSA ARSB CDH23 ERCC2 GAL3ST1 GALC
2 growth/size/body region MP:0005378 10.37 ARSB CDH23 ERCC2 GALC GLA HEXA
3 homeostasis/metabolism MP:0005376 10.35 ARSA ARSB CDH23 ERCC2 GAL3ST1 GALC
4 cellular MP:0005384 10.33 ARSB CDH23 ERCC2 GAL3ST1 GALC GLA
5 immune system MP:0005387 10.27 ARSA CDH23 ERCC2 GALC GLA IDUA
6 hematopoietic system MP:0005397 10.24 ARSA ARSB CDH23 ERCC2 GALC IDUA
7 mortality/aging MP:0010768 10.22 CDH23 ERCC2 GAL3ST1 GALC GLA HEXA
8 nervous system MP:0003631 10.22 ARSA ARSB CDH23 ERCC2 GAL3ST1 GALC
9 craniofacial MP:0005382 10.08 ARSB CDH23 GALC HEXA IDUA SLC6A3
10 hearing/vestibular/ear MP:0005377 10.05 ARSA ARSB CDH23 HEXA IDUA PLP1
11 liver/biliary system MP:0005370 9.98 GALC GLA HEXA IDUA PSAP SCP2
12 muscle MP:0005369 9.91 ARSB GALC GLA IDUA PLP1 PSAP
13 reproductive system MP:0005389 9.9 ARSB CDH23 ERCC2 GAL3ST1 HEXA IDUA
14 renal/urinary system MP:0005367 9.8 ARSB GAL3ST1 GALC GLA HEXA IDUA
15 skeleton MP:0005390 9.7 ARSB CDH23 ERCC2 GALC HEXA IDUA
16 vision/eye MP:0005391 9.32 ARSB CDH23 ERCC2 GALC GLA HEXA

Drugs & Therapeutics for Metachromatic Leukodystrophy

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

(show all 50)
# 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 phosphate Approved, Vet_approved Phase 2, Phase 3 302-25-0
5
Methylprednisolone hemisuccinate Approved Phase 2, Phase 3 2921-57-5
6 Prednisolone acetate Approved, Vet_approved Phase 2, Phase 3 52-21-1
7
Prednisolone Approved, Vet_approved Phase 2, Phase 3 50-24-8 5755
8
Prednisolone hemisuccinate Experimental Phase 2, Phase 3 2920-86-7
9 Antirheumatic Agents Phase 2, Phase 3
10 Antilymphocyte Serum Phase 2, Phase 3
11 Methylprednisolone Acetate Phase 2, Phase 3
12
tannic acid Approved Phase 2 1401-55-4
13
Mesna Approved, Investigational Phase 2 3375-50-6 598
14
Clotrimazole Approved, Vet_approved Phase 2 23593-75-1 2812
15
Miconazole Approved, Investigational, Vet_approved Phase 2 22916-47-8 4189
16
Mycophenolic acid Approved Phase 2 24280-93-1 446541
17
Benzocaine Approved, Investigational Phase 2 94-09-7, 1994-09-7 2337
18
Clofarabine Approved, Investigational Phase 2 123318-82-1 119182
19
alemtuzumab Approved, Investigational Phase 2 216503-57-0
20
Hydroxyurea Approved Phase 2 127-07-1 3657
21
Melphalan Approved Phase 2 148-82-3 460612 4053
22
Celecoxib Approved, Investigational Phase 2 169590-42-5 2662
23
Acetylcysteine Approved, Investigational Phase 2 616-91-1 12035
24
Fludarabine Approved Phase 2 21679-14-1, 75607-67-9 30751
25
rituximab Approved Phase 2 174722-31-7 10201696
26
Tocopherol Approved, Investigational Phase 2 1406-66-2, 54-28-4 14986
27
Thiotepa Approved, Investigational Phase 2 52-24-4 5453
28
Vitamin E Approved, Nutraceutical, Vet_approved Phase 2 59-02-9 14985
29 Tocotrienol Investigational Phase 2 6829-55-6
30 Antitubercular Agents Phase 2
31 Anti-Infective Agents Phase 2
32 Anti-Bacterial Agents Phase 2
33 Dermatologic Agents Phase 2
34 Antifungal Agents Phase 2
35 Cyclosporins Phase 2
36 Calcineurin Inhibitors Phase 2
37 Antibiotics, Antitubercular Phase 2
38 Antimetabolites Phase 2
39 Antineoplastic Agents, Immunological Phase 2
40 Immunosuppressive Agents Phase 2
41 Alkylating Agents Phase 2
42 Immunologic Factors Phase 2
43 Alpha-lipoic Acid Phase 2
44 Vitamins Phase 2
45 Thioctic Acid Phase 2
46 Tocopherols Phase 2
47 Tocotrienols Phase 2
48 N-monoacetylcystine Phase 2
49
Warfarin Approved 81-81-2 6691 54678486
50 Anticoagulants

Interventional clinical trials:

(show all 37)
# Name Status NCT ID Phase Drugs
1 Treatment of Lysosomal and Peroxisomal Inborn Errors of Metabolism by Bone Marrow Transplantation Completed NCT00176904 Phase 2, Phase 3 Busulfan, Cyclophosphamide, Antithymocyte Globulin
2 An Open Label, Non-randomized Trial to Evaluate the Safety and Efficacy of a Single Infusion of OTL-200 in Patients With Late Juvenile (LJ) Metachromatic Leukodystrophy (MLD). Recruiting NCT04283227 Phase 3
3 A Phase III Trial of ALD-101 Adjuvant Therapy of Unrelated Umbilical Cord Blood Transplantation (UCBT) in Patients With Inborn Errors of Metabolism Terminated NCT00654433 Phase 3
4 A Phase I/II, Open Labeled, Monocentric Study of Direct Intracranial Administration of a Replication Deficient Adeno-associated Virus Gene Transfer Vector Serotype rh.10 Expressing the Human ARSA cDNA to Children With Metachromatic Leukodystrophy. Unknown status NCT01801709 Phase 1, Phase 2
5 A Single Center, Open-Label, Non-Randomized, Uncontrolled, Multiple-Dose, Dose Escalation Study of the Safety, Pharmacokinetics, Efficacy and Long Term Safety of HGT-1111 (Recombinant Human Arylsulfatase A [rhASA, Metazym]) for the Treatment of Patients With Late Infantile Metachromatic Leukodystrophy (MLD) Completed NCT00633139 Phase 1, Phase 2
6 A Phase I/II Multicenter Open-label Dose Escalation Study of HGT-1110 Administered Intrathecally in Children With Metachromatic Leukodystrophy Completed NCT01510028 Phase 1, Phase 2
7 and Safety of METAZYM (Recombinant Human Arylsulfatase A or rhASA) for the Treatment of Patients With Late Infantile MLD Who Had Previously Hematopoietic Stem Cell Transplantation Completed NCT01303146 Phase 2 rhARSA
8 Allogeneic Hematopoietic Stem Cell Transplantation for Standard Risk Inherited Metabolic Disorders Completed NCT01043640 Phase 2 Campath-1H;Cyclophosphamide;Busulfan;Cyclosporine A;Mycophenolate Mofetil
9 Treatment of High Risk, Inherited Lysosomal And Peroxisomal Disorders by Reduced Intensity Hematopoietic Stem Cell Transplantation Completed NCT00383448 Phase 2 Clofarabine;Melphalan;Alemtuzumab;mycophenylate mofetil;Hydroxyurea
10 A Global, Multicenter, Open-label, Matched Historical Control Study of Intrathecal SHP611 in Subjects With Late Infantile Metachromatic Leukodystrophy Recruiting NCT03771898 Phase 2 SHP611
11 A Phase I/II Clinical Trial of Lentiviral Hematopoietic Stem Cell Gene Therapy for Treatment of Developed Metachromatic Leukodystrophy and Adrenoleukodystrophy Recruiting NCT02559830 Phase 1, Phase 2
12 MT2013-31: Allogeneic Hematopoietic Cell Transplantation for Inherited Metabolic Disorders and Severe Osteopetrosis Following Conditioning With Busulfan (Therapeutic Drug Monitoring), Fludarabine +/- ATG Recruiting NCT02171104 Phase 2 IMD Preparative Regimen;Osteopetrosis Only Preparative Regimen;Osteopetrosis Haploidentical Only Preparative Regimen;cALD SR-A (Standard-Risk, Regimen A);cALD SR-B (Standard-Risk, Regimen B);cALD HR-D (High-Risk, Regimen C);cALD HR-D (High-Risk, Regimen D)
13 A Phase 2, Single-arm, Open-label Study to Evaluate the Safety and Efficacy of MGTA-456 in Patients With Inherited Metabolic Disorders (IMD) Undergoing Hematopoietic Stem Cell Transplantation (HSCT) Recruiting NCT03406962 Phase 2 MGTA-456
14 A Phase II Study of Reduced Intensity Conditioning in Pediatric Patients and Young Adults ≤55 Years of Age With Non-Malignant Disorders Undergoing Umbilical Cord Blood, Bone Marrow, or Peripheral Blood Stem Cell Transplantation Recruiting NCT01962415 Phase 2 Hydroxyurea;Alemtuzumab;Fludarabine;Melphalan;Thiotepa
15 A Phase I/II Clinical Trial of Hematopoietic Stem Cell Gene Therapy for the Treatment of Metachromatic Leukodystrophy Active, not recruiting NCT01560182 Phase 1, Phase 2
16 A Single Arm, Open Label, Clinical Study of Cryopreserved Autologous CD34+ Cells Transduced With Lentiviral Vector Containing Human ARSA cDNA (OTL-200), for the Treatment of Early Onset Metachromatic Leukodystrophy (MLD) Active, not recruiting NCT03392987 Phase 2
17 An Open-Label Extension of Study HGT-MLD-070 Evaluating Long Term Safety and Efficacy of Intrathecal Administration of HGT-1110 in Patients With Metachromatic Leukodystrophy Active, not recruiting NCT01887938 Phase 1, Phase 2
18 Phase I/II Pilot Study of Mixed Chimerism to Treat Inherited Metabolic Disorders Active, not recruiting NCT01372228 Phase 1, Phase 2
19 A Multi-center, Open-Label Extension Study of HGT-1111 (Recombinant Human Arylsulfatase A or rhASA) Treatment in Patients With Late Infantile Metachromatic Leukodystrophy (MLD) Terminated NCT00681811 Phase 2 HGT-1111
20 A Single Center, Open-label, Non-randomized, Uncontrolled, Multiple-dose, Dose Escalation Study of the Safety, Pharmacokinetics and Efficacy of Metazym for the Treatment of Patients With Late Infantile Metachromatic Leukodystrophy (MLD) Completed NCT00418561 Phase 1 rhASA
21 Augmentation of Umbilical Cord Blood Transplantation for Inherited Metabolic Diseases With Intrathecal Administration of Human Umbilical Cord Blood-Derived Oligodendrocyte-Like Cells Recruiting NCT02254863 Phase 1
22 A Single-Arm Study to Assess the Safety of Transplantation With Human Placental-Derived Stem-Cells Combined With Unrelated and Related Cord Blood in Subjects With Certain Malignant Hematologic Diseases and Non-Malignant Disorders Active, not recruiting NCT01586455 Phase 1 Human Placental Derived Stem Cell
23 Treatment of Early Infantile-Onset Lysosomal Storage Diseases With Fetal Umbilical Cord Blood (UCB) Transplantation Withdrawn NCT01003912 Phase 1
24 Study of Pulmonary Complications in Pediatric Patients With Storage Disorders Undergoing Allogeneic Hematopoietic Stem Cell Transplantation Unknown status NCT00005900
25 Effect of Warfarin in the Treatment of Metachromatic Leukodystrophy Completed NCT00683189 Warfarin
26 Study of the Natural History of Cerebral White Matter Involvement in Metachromatic Leukodystrophy, Using High-field MRI and Diffusion Tensor Imaging Completed NCT01325025
27 Stem Cell Transplantation (SCT) for Genetic Diseases Completed NCT00004378
28 Treatment of High Risk, Inherited Lysosomal and Peroxisomal Disorders by Reduced-Intensity Hematopoietic Cell Transplantation and Low-Dose Total Body Irradiation With Marrow Boosting by Volumetric-Modulated Arc Therapy (VMAT) Completed NCT01626092 Campath-1H;Clofarabine;Melphalan;Cyclosporine A;Mycophenolate mofetil
29 Unrelated Donor Bone Marrow Transplantation for Definitive Treatment of Patients With Phosphoglycerate Kinase (PGK) Deficiency Completed NCT00592540
30 Gene Therapy for Metachromatic Leukodystrophy (MLD) Using a Self-inactivating Lentiviral Vector (TYF-ARSA) Recruiting NCT03725670
31 The Natural History of Metachromatic Leukodystrophy Active, not recruiting NCT00639132
32 Biomarker for Metachromatic Leukodystrophy Disease AN INTERNATIONAL, MULTICENTER, EPIDEMIOLOGICAL PROTOCOL Active, not recruiting NCT01536327
33 A Follow-Up Study to Evaluate the Safety and Clinical Outcomes of Patients With Non-Malignant Disease Who Have Undergone Hematopoietic Stem Cell Transplantation With MGTA-456 Enrolling by invitation NCT04008849
34 Allogeneic Stem Cell Transplantation for the Treatment of Multiple Sclerosis (Compassionate Use) No longer available NCT02084121
35 Single Patient Expanded Access Protocol: Phase I/II Pilot Study of Mixed Chimerism to Treat Inherited Metabolic Disorders No longer available NCT02021266
36 Expanded Access Protocol for CaspaCIDe T Cells From An HLA-Partially Matched Related Donor After Negative Selection of TCR αβ+T Cells In Pediatric Patients Affected by Hematological and Other Disorders No longer available NCT03639844 rimiducid
37 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:

# Genetic test Affiliating Genes
1 Metachromatic Leukodystrophy 29 ARSA

Anatomical Context for Metachromatic Leukodystrophy

MalaCards organs/tissues related to Metachromatic Leukodystrophy:

40
Brain, Bone, Bone Marrow, Spinal Cord, Skin, Liver, Kidney

Publications for Metachromatic Leukodystrophy

Articles related to Metachromatic Leukodystrophy:

(show top 50) (show all 1177)
# Title Authors PMID Year
1
Two new arylsulfatase A (ARSA) mutations in a juvenile metachromatic leukodystrophy (MLD) patient. 61 54 56 24 6
1684088 1991
2
Molecular basis of different forms of metachromatic leukodystrophy. 54 6 56 61 24
1670590 1991
3
Contribution of arylsulfatase A mutations located on the same allele to enzyme activity reduction and metachromatic leukodystrophy severity. 6 56 24 61
11941485 2002
4
Multiple mutations are responsible for the high frequency of metachromatic leukodystrophy in a small geographic area. 56 6 61 54
7825603 1995
5
An 11-bp deletion in the arylsulfatase A gene of a patient with late infantile metachromatic leukodystrophy. 56 54 61 6
1676699 1991
6
Identification of a mutation in the arylsulfatase A gene of a patient with adult-type metachromatic leukodystrophy. 61 54 56 6
1673291 1991
7
Metachromatic leukodystrophy: identification of the first deletion in exon 1 and of nine novel point mutations in the arylsulfatase A gene. 6 61 54 24
9090526 1997
8
Arylsulfatase A pseudodeficiency: loss of a polyadenylylation signal and N-glycosylation site. 61 56 6
2574462 1989
9
Lysosomal storage diseases: diagnostic confirmation and management of presymptomatic individuals. 61 24 56
21502868 2011
10
Umbilical cord blood transplantation for juvenile metachromatic leukodystrophy. 24 56 61
19067349 2008
11
Metachromatic leukodystrophy - mutation analysis provides further evidence of genotype-phenotype correlation. 24 56 61
18786133 2008
12
Late-onset metachromatic leukodystrophy: genotype strongly influences phenotype. 61 56 24
16966551 2006
13
Enzyme replacement improves nervous system pathology and function in a mouse model for metachromatic leukodystrophy. 56 61 24
15772092 2005
14
Prevalence of common mutations in the arylsulphatase A gene in metachromatic leukodystrophy patients diagnosed in Britain. 61 6 24
8095918 1993
15
Prosaposin deficiency and saposin B deficiency (activator-deficient metachromatic leukodystrophy): report on two patients detected by analysis of urinary sphingolipids and carrying novel PSAP gene mutations. 61 54 6
19267410 2009
16
Adult onset metachromatic leukodystrophy without electroclinical peripheral nervous system involvement: a new mutation in the ARSA gene. 54 56 61
15710861 2005
17
Biochemical characterization of two (C300F, P425T) arylsulfatase a missense mutations. 6 54 61
12503099 2003
18
Metachromatic leucodystrophy in Portugal-finding of four new molecular lesions: C300F, P425T, g.1190-1191insC, and g.2408delC. Mutations in brief no. 232. Online. 24 6
10220151 1999
19
Coincidence of two novel arylsulfatase A alleles and mutation 459+1G>A within a family with metachromatic leukodystrophy: molecular basis of phenotypic heterogeneity. 61 54 56
9888390 1999
20
Phenotype of arylsulfatase A-deficient mice: relationship to human metachromatic leukodystrophy. 61 54 56
8962139 1996
21
Late infantile metachromatic leukodystrophy in Israel. 61 54 56
7858169 1994
22
Complex arylsulfatase A alleles causing metachromatic leukodystrophy. 6 61 54
7981715 1994
23
An adult-type metachromatic leukodystrophy caused by substitution of serine for glycine-122 in arylsulfatase A. 61 6 54
7902317 1993
24
High residual arylsulfatase A (ARSA) activity in a patient with late-infantile metachromatic leukodystrophy. 6 54 61
8101038 1993
25
Mutations in the arylsulfatase A pseudodeficiency allele causing metachromatic leukodystrophy. 56 61 54
1678251 1991
26
Genotype-phenotype relationship in various degrees of arylsulfatase A deficiency. 54 56 61
1673113 1991
27
An assay for the rapid detection of the arylsulfatase A pseudodeficiency allele facilitates diagnosis and genetic counseling for metachromatic leukodystrophy. 61 54 6
1671769 1991
28
Characterization of a mutation in a family with saposin B deficiency: a glycosylation site defect. 6 54 61
2320574 1990
29
Insertion in the mRNA of a metachromatic leukodystrophy patient with sphingolipid activator protein-1 deficiency. 54 6 61
1689485 1990
30
Detection of a point mutation in sphingolipid activator protein-1 mRNA in patients with a variant form of metachromatic leukodystrophy. 54 61 6
2302219 1990
31
The burden of inherited leukodystrophies in children. 61 56
20660364 2010
32
Molecular analysis of ARSA and PSAP genes in twenty-one Italian patients with metachromatic leukodystrophy: identification and functional characterization of 11 novel ARSA alleles. 54 24 61
18693274 2008
33
Stabilization of juvenile metachromatic leukodystrophy after bone marrow transplantation: a 13-year follow-up. 54 61 24
17890417 2007
34
ARSA gene mutations in five Chinese metachromatic leukodystrophy patients. 54 61 24
17560502 2007
35
Somatic intragenic recombination of the arylsulfatase A gene in a metachromatic leukodystrophy patient. 54 61 24
16782379 2006
36
Novel mutations in the arylsulfatase A gene in eight Italian families with metachromatic leukodystrophy. 24 54 61
16678723 2006
37
Arylsulfatase A Deficiency 6 61
20301309 2006
38
Mutations c.459+1G>A and p.P426L in the ARSA gene: prevalence in metachromatic leukodystrophy patients from European countries. 24 61 54
16140556 2005
39
Expression and purification of a human, soluble Arylsulfatase A for Metachromatic Leukodystrophy enzyme replacement therapy. 54 61 24
15862354 2005
40
Missense mutations as a cause of metachromatic leukodystrophy. Degradation of arylsulfatase A in the endoplasmic reticulum. 24 54 61
15720392 2005
41
Infantile metachromatic leukodystrophy (MLD) in a compound heterozygote for the c.459 + 1G > A mutation and a complete deletion of the ARSA gene. 61 54 24
15211666 2004
42
Novel mutations in arylsulfatase A gene in three Ukrainian families with metachromatic leukodystrophy. 54 61 24
14680985 2003
43
Oligomerization capacity of two arylsulfatase A mutants: C300F and P425T. 6 61
12788103 2003
44
High prevalence of I179S mutation in patients with late-onset metachromatic leukodystrophy. 6 61
12081727 2002
45
Defective oligomerization of arylsulfatase a as a cause of its instability in lysosomes and metachromatic leukodystrophy. 54 24 61
11777924 2002
46
Late-onset metachromatic leukodystrophy clinically presenting as isolated peripheral neuropathy: compound heterozygosity for the IVS2+1G-->A mutation and a newly identified missense mutation (Thr408Ile) in a Spanish family. 61 6
11456299 2001
47
Metachromatic leukodystrophy in the Navajo: fallout of the American-Indian wars of the nineteenth century. 61 56
11424134 2001
48
Variable onset of metachromatic leukodystrophy in a Vietnamese family. 24 54 61
11020646 2000
49
A non-glycosylated and functionally deficient mutant (N215H) of the sphingolipid activator protein B (SAP-B) in a novel case of metachromatic leukodystrophy (MLD). 6 61
10682309 2000
50
Identification of 12 novel mutations and two new polymorphisms in the arylsulfatase A gene: haplotype and genotype-phenotype correlation studies in Spanish metachromatic leukodystrophy patients. 61 54 24
10477432 1999

Variations for Metachromatic Leukodystrophy

ClinVar genetic disease variations for Metachromatic Leukodystrophy:

6 (show top 50) (show all 373) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 ARSA NM_000487.6(ARSA):c.*96A>GSNV Benign, other 3049 rs6151429 22:51063477-51063477 22:50625049-50625049
2 ARSA NM_000487.6(ARSA):c.1055A>G (p.Asn352Ser)SNV Benign/Likely benign, other 3050 rs2071421 22:51064416-51064416 22:50625988-50625988
3 ARSA NM_000487.6(ARSA):c.465+1G>ASNV Pathogenic 3051 rs80338815 22:51065593-51065593 22:50627165-50627165
4 ARSA NM_000487.6(ARSA):c.1283C>T (p.Pro428Leu)SNV Pathogenic 3052 rs28940893 22:51063820-51063820 22:50625392-50625392
5 ARSA ARSA, 11-BP DEL, EX8deletion Pathogenic 3055
6 ARSA ARSA, 1-BP DEL, 447Cdeletion Pathogenic 3056
7 ARSA NM_000487.6(ARSA):c.542T>G (p.Ile181Ser)SNV Pathogenic 3057 rs74315457 22:51065404-51065404 22:50626976-50626976
8 ARSA NM_000487.6(ARSA):c.1210+1G>ASNV Pathogenic 3058 rs80338820 22:51064006-51064006 22:50625578-50625578
9 ARSA ARSA, 1-BP DEL, 297Cdeletion Pathogenic 3065
10 ARSA NM_000487.6(ARSA):c.467G>A (p.Gly156Asp)SNV Pathogenic 3066 rs74315463 22:51065479-51065479 22:50627051-50627051
11 ARSA NM_000487.6(ARSA):c.506C>G (p.Pro169Arg)SNV Pathogenic 3068 rs74315465 22:51065440-51065440 22:50627012-50627012
12 ARSB NM_000046.5(ARSB):c.629A>G (p.Tyr210Cys)SNV Pathogenic 885 rs118203943 5:78260300-78260300 5:78964477-78964477
13 ARSA NM_000487.6(ARSA):c.641C>T (p.Ala214Val)SNV Pathogenic 3070 rs74315467 22:51065305-51065305 22:50626877-50626877
14 ARSA NM_000487.6(ARSA):c.697C>A (p.Pro233Thr)SNV Pathogenic 3072 rs74315469 22:51065176-51065176 22:50626748-50626748
15 ARSA NM_000487.6(ARSA):c.890C>A (p.Ser297Tyr)SNV Pathogenic 3078 rs74315474 22:51064671-51064671 22:50626243-50626243
16 ARSA NM_000487.6(ARSA):c.1198_1200TTC[1] (p.Phe401del)short repeat Pathogenic 3086 rs1569077723 22:51064014-51064016 22:50625586-50625588
17 ARSA NM_000487.6(ARSA):c.1229C>T (p.Thr410Ile)SNV Pathogenic 3092 rs28940895 22:51063874-51063874 22:50625446-50625446
18 ARSA NM_000487.6(ARSA):c.905G>T (p.Cys302Phe)SNV Pathogenic 3093 rs74315484 22:51064656-51064656 22:50626228-50626228
19 ARSA NM_000487.6(ARSA):c.1279C>A (p.Pro427Thr)SNV Pathogenic 3094 rs74315485 22:51063824-51063824 22:50625396-50625396
20 ARSA NM_000487.6(ARSA):c.257G>A (p.Arg86Gln)SNV Pathogenic 21186 rs74315458 22:51065802-51065802 22:50627374-50627374
21 ARSA NM_000487.6(ARSA):c.769G>C (p.Asp257His)SNV Pathogenic 21187 rs80338819 22:51065104-51065104 22:50626676-50626676
22 ARSA NM_000487.6(ARSA):c.410T>C (p.Leu137Pro)SNV Pathogenic 3089 rs121434215 22:51065649-51065649 22:50627221-50627221
23 ARSA NM_000487.6(ARSA):c.862A>C (p.Thr288Pro)SNV Pathogenic 3090 rs28940894 22:51064699-51064699 22:50626271-50626271
24 ARSA NM_000487.6(ARSA):c.302G>T (p.Gly101Val)SNV Pathogenic 68129 rs74315455 22:51065757-51065757 22:50627329-50627329
25 ARSA NM_000487.6(ARSA):c.929G>T (p.Gly310Val)SNV Pathogenic 68164 rs199476356 22:51064632-51064632 22:50626204-50626204
26 ARSA NM_000487.6(ARSA):c.925G>A (p.Glu309Lys)SNV Pathogenic 68162 rs199476360 22:51064636-51064636 22:50626208-50626208
27 ARSA NM_000487.6(ARSA):c.1108-2A>GSNV Pathogenic 93115 rs398123411 22:51064111-51064111 22:50625683-50625683
28 ARSA NM_000487.6(ARSA):c.1408_1418del (p.Ala470fs)deletion Pathogenic 198735 rs80338823 22:51063685-51063695 22:50625257-50625267
29 ARSA NM_000487.6(ARSA):c.474C>A (p.Cys158Ter)SNV Pathogenic 265461 rs768028181 22:51065472-51065472 22:50627044-50627044
30 ARSA NM_000487.6(ARSA):c.346C>T (p.Arg116Ter)SNV Pathogenic 280950 rs761860059 22:51065713-51065713 22:50627285-50627285
31 ARSA NM_000487.6(ARSA):c.1274A>G (p.His425Arg)SNV Pathogenic 431090 rs1135401757 22:51063829-51063829 22:50625401-50625401
32 ARSA NM_000487.6(ARSA):c.852T>A (p.Asn284Lys)SNV Pathogenic 431089 rs1135401756 22:51065021-51065021 22:50626593-50626593
33 ARSA NM_000487.6(ARSA):c.545C>G (p.Pro182Arg)SNV Pathogenic 431086 rs1135401755 22:51065401-51065401 22:50626973-50626973
34 ARSA NM_000487.6(ARSA):c.229G>C (p.Ala77Pro)SNV Pathogenic 431085 rs763880042 22:51065830-51065830 22:50627402-50627402
35 ARSA NM_000487.6(ARSA):c.98T>C (p.Leu33Pro)SNV Pathogenic 431084 rs1135401754 22:51066110-51066110 22:50627682-50627682
36 ARSA NM_000487.6(ARSA):c.937C>T (p.Arg313Ter)SNV Pathogenic 434394 rs551472773 22:51064624-51064624 22:50626196-50626196
37 ARSA NM_000487.6(ARSA):c.960G>A (p.Trp320Ter)SNV Pathogenic 495883 rs1375757476 22:51064601-51064601 22:50626173-50626173
38 ARSA NC_000022.11:g.(?_50625125)_(50627799_?)deldeletion Pathogenic 526831 22:51063553-51066227 22:50625125-50627799
39 ARSA NM_000487.6(ARSA):c.1046del (p.Pro349fs)deletion Pathogenic 661357 22:51064425-51064425 22:50625997-50625997
40 ARSB NM_000046.5(ARSB):c.427del (p.Val143fs)deletion Pathogenic 559782 rs766914147 5:78264901-78264901 5:78969078-78969078
41 ARSA NM_000487.6(ARSA):c.157C>T (p.Gln53Ter)SNV Pathogenic 651844 22:51066051-51066051 22:50627623-50627623
42 ARSA NM_000487.6(ARSA):c.1366C>T (p.Gln456Ter)SNV Pathogenic 800502 22:51063737-51063737 22:50625309-50625309
43 ARSA NM_000487.6(ARSA):c.956_958del (p.Phe319del)deletion Pathogenic 800501 22:51064603-51064605 22:50626175-50626177
44 ARSA NM_000487.6(ARSA):c.712C>T (p.Gln238Ter)SNV Pathogenic 800498 22:51065161-51065161 22:50626733-50626733
45 ARSA NM_000487.6(ARSA):c.685-1G>ASNV Pathogenic 800497 22:51065189-51065189 22:50626761-50626761
46 ARSA NM_000487.6(ARSA):c.1087dup (p.Leu363fs)duplication Pathogenic 858399 22:51064383-51064384 22:50625955-50625956
47 ARSA NM_000487.6(ARSA):c.433C>T (p.Arg145Ter)SNV Pathogenic 840281 22:51065626-51065626 22:50627198-50627198
48 ARSA NM_000487.6(ARSA):c.855-1G>ASNV Pathogenic 840642 22:51064707-51064707 22:50626279-50626279
49 ARSA NC_000022.11:g.50627051deldeletion Pathogenic 856376
50 ARSA NM_000487.6(ARSA):c.418dup (p.His140fs)duplication Pathogenic 370305 rs745884435 22:51065640-51065641 22:50627212-50627213

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

73 (show top 50) (show all 97)
# 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

Copy number variations for Metachromatic Leukodystrophy from CNVD:

7
# CNVD ID Chromosome 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

Pathways related to Metachromatic Leukodystrophy according to KEGG:

36
# Name Kegg Source Accession
1 Sphingolipid metabolism hsa00600
2 Lysosome hsa04142

GO Terms for Metachromatic Leukodystrophy

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

# Name GO ID Score Top Affiliating Genes
1 lysosome GO:0005764 9.65 STS PSAP MPZ IDUA HEXA GLA
2 endoplasmic reticulum lumen GO:0005788 9.55 SUMF1 STS ARSH ARSB ARSA
3 azurophil granule lumen GO:0035578 9.43 GLA ARSB ARSA
4 lysosomal lumen GO:0043202 9.23 PSAP IDUA HEXA GLA GALC CTSL

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

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 9.91 UGT8 STS PSAP GALC GAL3ST1
2 metabolic process GO:0008152 9.76 IDUA HEXA GLA GALC
3 central nervous system development GO:0007417 9.67 UGT8 MAL ARSB ARSA
4 lysosomal transport GO:0007041 9.52 PSAP ARSB
5 response to pH GO:0009268 9.49 ARSB ARSA
6 response to methylmercury GO:0051597 9.48 ARSB ARSA
7 sphingolipid metabolic process GO:0006665 9.46 UGT8 PSAP GALC GAL3ST1
8 galactosylceramide biosynthetic process GO:0006682 9.43 UGT8 GAL3ST1
9 chondroitin sulfate catabolic process GO:0030207 9.43 IDUA HEXA ARSB
10 myelination GO:0042552 9.43 PSAP PLP1 MPZ MAL GALC GAL3ST1
11 protein localization to paranode region of axon GO:0002175 9.4 UGT8 MAL
12 galactosylceramide catabolic process GO:0006683 9.32 PSAP GALC
13 glycosphingolipid metabolic process GO:0006687 9.23 UGT8 SUMF1 STS PSAP HEXA GLA

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

# Name GO ID Score Top Affiliating Genes
1 hydrolase activity GO:0016787 9.96 STS IDUA HEXA GLA GALC ERCC2
2 catalytic activity GO:0003824 9.7 STS SCP2 GLA GALC ARSH ARSB
3 hydrolase activity, acting on glycosyl bonds GO:0016798 9.62 IDUA HEXA GLA GALC
4 hydrolase activity, hydrolyzing O-glycosyl compounds GO:0004553 9.54 IDUA HEXA GLA
5 structural constituent of myelin sheath GO:0019911 9.4 PLP1 MAL
6 sulfuric ester hydrolase activity GO:0008484 9.26 STS ARSH ARSB ARSA
7 arylsulfatase activity GO:0004065 8.92 STS ARSH ARSB ARSA

Sources for Metachromatic Leukodystrophy

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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