MCID: LKD001
MIFTS: 59

Leukodystrophy

Categories: Neuronal diseases, Rare diseases
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Aliases & Classifications for Leukodystrophy

MalaCards integrated aliases for Leukodystrophy:

Name: Leukodystrophy 11 19 52 58 75 28 53 5 14 71
Leukodystrophies 41 33

Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

Disease Ontology 11 DOID:10579
ICD9CM 34 330.0
NCIt 49 C61253
SNOMED-CT 68 5101009
ICD10 via Orphanet 32 E75.2
UMLS via Orphanet 72 C0023520
Orphanet 58 ORPHA68356
UMLS 71 C0023520

Summaries for Leukodystrophy

MedlinePlus: 41 What are leukodystrophies? Leukodystrophies are a group of rare genetic disorders that affect the central nervous system (CNS). The CNS is made up of your brain and spinal cord. Leukodystrophies damage the white matter of your CNS. The white matter includes: Nerve fibers, also called axons, which connect your nerve cells Myelin, a layer of proteins and fatty materials that covers and protects the nerve fibers. It also helps speed up signals between the nerve cells. When the white matter is damaged, it can slow down or block the signals between nerve cells. This can cause many different symptoms, including trouble with movement, vision, hearing, and thinking. There are over 50 types of leukodystrophies. Some types are present at birth, while others may not cause symptoms until a child becomes a toddler. A few types mainly affect adults. Most types get worse over time. What causes leukodystrophies? Leukodystrophies are caused by genetic changes. These changes are usually inherited, meaning that they are passed from parent to child. What are the symptoms of leukodystrophies? The symptoms of leukodystrophies depend on the type; they can include a gradual loss of: Muscle tone balance and mobility Walking Speech Ability to eat Vision Hearing Behavior There can also be other symptoms, such as: Learning disabilities bladder issues Breathing problems Developmental disabilities Muscle control disorders Seizures How are leukodystrophies diagnosed? Leukodystrophies can be hard to diagnose because there are so many different types which can have different symptoms. Your health care provider may use many tools to make a diagnosis: Physical and neurological exams A medical history, including asking about family history Imaging tests, such as an MRI or CT scan Genetic testing to look for genetic changes that could cause leukodystrophies Lab tests What are the treatments for leukodystrophies? There is no cure for leukodystrophies. Treatment focuses on relieving symptoms and providing support. It may include: Medicines to manage muscle tone, seizures, and spasticity (muscle stiffness) Physical, occupational, and speech therapies to improve mobility, function, and cognitive problems Nutritional therapy for eating and swallowing problems Educational and recreational programs Stem cell or bone marrow transplantation can be helpful for a few types of leukodystrophy. One type of leukodystrophy, CTX, is treatable if it is diagnosed early. It is treated with chenodeoxycholic acid (CDCA) replacement therapy. NIH: National Institute of Neurological Disorders and Stroke

MalaCards based summary: Leukodystrophy, also known as leukodystrophies, is related to metachromatic leukodystrophy and krabbe disease, and has symptoms including tremor, back pain and headache. An important gene associated with Leukodystrophy is EIF2B5 (Eukaryotic Translation Initiation Factor 2B Subunit Epsilon), and among its related pathways/superpathways are Neural Stem Cells and Lineage-specific Markers and Translation factors. The drugs Prednisolone phosphate and Prednisolone acetate have been mentioned in the context of this disorder. Affiliated tissues include spinal cord, bone marrow and brain, and related phenotypes are Increased shRNA abundance (Z-score > 2) and Reduced mammosphere formation

NINDS: 52 Leukodystrophy is not a single disorder. The term refers to a group of rare, primarily inherited neurological disorders known as the leukodystrophies that result from the abnormal production, processing, or development of myelin and other components of central nervous system (CNS) white matter, such as cells called oligodendrocytes and astrocytes. All leukodystrophies are the result of genetic defects (mutations). Some forms are present at birth, while others may not produce symptoms until a child becomes a toddler. A few mostly affects adults. More than 50 different leukodystrophies have been identified, among them: Alexander disease autosomal dominant leukodystrophy with autonomic diseases (ADLD) Canavan disease cerebrotendinous xanthomatosis (CTX) metachromatic leukodystrophy (MLD) Pelizaeus-Merzbacher disease, and Refsum disease. Symptoms vary according to the specific type and may be difficult to recognize in the early stages of the disorder. Each type of leukodystrophy affects myelin differently and in different parts of the CNS, leading to a range of symptoms. The most common symptom is a gradual functional decline in an infant or child who previously appeared well. Progressive loss may appear in: muscle tone balance and mobility walking (gait) speech ability to eat vision hearing behavior

GARD: 19 A Leukodystrophy is a type of rare genetic disorder that affects the brain, spinal cord, and other nerves in the body. It is caused by destruction of the white matter of the brain. The white matter degrades due to defects of the myelin, which is a fatty covering that insulates nerves in the brain. Myelin is needed to protect the nerves and the nerves can't function normally without it. These disorders are progressive, meaning they tend to get worse with time. The leukodystrophies are a group of disorders caused by spelling mistakes in the genes involved in making myelin. Specific leukodystrophies include metachromatic Leukodystrophy, Krabbe Leukodystrophy, X-linked adrenoLeukodystrophy, Pelizaeus-Merzbacher disease, Canavan disease, and Alexander disease. The most common symptom of a Leukodystrophy is a decline in functioning of an infant or child who previously appeared healthy. This gradual loss may be seen with issues in body tone, movements, gait, speech, ability to eat, vision, hearing, and behavior.

Disease Ontology: 11 A cerebral degeneration characterized by dysfunction of the white matter of the brain.

Wikipedia: 75 Leukodystrophies are a group of usually inherited disorders characterized by degeneration of the white... more...

Related Diseases for Leukodystrophy

Diseases in the Leukodystrophy family:

Lmnb1-Related Autosomal Dominant Leukodystrophy Tubb4a-Related Leukodystrophy

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

(show top 50) (show all 648)
# Related Disease Score Top Affiliating Genes
1 metachromatic leukodystrophy 33.8 PSAP PLP1 GFAP GALC ARSA
2 krabbe disease 33.4 PSAP PLP1 GALC ARSA
3 pelizaeus-merzbacher disease 33.3 TUBB4A SOX10 POLR3B PLP1 GFAP GALC
4 leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism 33.2 TMEM63A POLR3B PLP1 EIF2B3
5 leukodystrophy, hypomyelinating, 6 33.2 TUBB4A POLR3B PLP1
6 leukodystrophy, hypomyelinating, 2 33.1 SOX10 PLP1 FA2H
7 leukoencephalopathy with vanishing white matter 33.1 POLR3B PLP1 GFAP EIF2B5 EIF2B3 EIF2B2
8 leukodystrophy, hypomyelinating, 13 33.1 POLR3B EIF2B3 EIF2B2
9 leukodystrophy, hypomyelinating, 11 33.1 TMEM63A POLR3B EIF2B3
10 leukodystrophy, hypomyelinating, 4 33.1 TUBB4A TMEM63A PLP1
11 leukodystrophy, hypomyelinating, 5 33.1 TUBB4A PLP1 GFAP GALC EIF2B5
12 leukodystrophy, hypomyelinating, 10 33.0 POLR3B EIF2B3 EIF2B2
13 leukodystrophy, hypomyelinating, 9 33.0 POLR3B EIF2B3
14 leukodystrophy, hypomyelinating, 3 33.0 PLP1 KARS1
15 hypomyelinating leukodystrophy 32.9 TUBB4A TMEM63A TMEM106B SOX10 POLR3B PLP1
16 leukodystrophy, hypomyelinating, 12 32.9 EIF2B3 EIF2B2
17 leukoencephalopathy, hereditary diffuse, with spheroids 1 32.9 TMEM106B EIF2B5 EIF2B3
18 megalencephalic leukoencephalopathy with subcortical cysts 32.9 TMEM63A PLP1 ARSA
19 peripheral demyelinating neuropathy, central dysmyelination, waardenburg syndrome, and hirschsprung disease 32.8 SOX10 POLR3B PLP1 EIF2B3 EIF2B2
20 leukodystrophy, demyelinating, adult-onset, autosomal dominant 32.8 PLP1 LMNB1
21 metachromatic leukodystrophy, juvenile form 32.7 PSAP ARSA
22 metachromatic leukodystrophy, late infantile form 32.7 PSAP ARSA
23 metachromatic leukodystrophy, adult form 32.5 PSAP ARSA
24 canavan disease 32.3 PLP1 GALC ARSA
25 spastic paraplegia 2, x-linked 32.2 PLP1 FA2H CNP
26 infantile krabbe disease 32.2 PSAP GALC
27 sphingolipidosis 32.1 PSAP GALC ARSA
28 demyelinating disease 31.5 PLP1 GFAP GALC ARSA
29 dystonia 31.3 TUBB4A LMNB1 FA2H EIF2B5 DEGS1
30 childhood ataxia with central nervous system hypomyelination / vanishing white matter 31.0 EIF2B5 EIF2B3 EIF2B2
31 nervous system disease 31.0 TUBB4A SOX10 PLP1 GFAP GALC EIF2B2
32 hereditary spastic paraplegia 31.0 TUBB4A PLP1 GALC FA2H
33 gaucher's disease 30.9 PSAP GALC ARSA
34 neuronal ceroid lipofuscinosis 30.8 TMEM106B PSAP GFAP GALC ARSA
35 spastic ataxia 30.8 POLR3B PLP1 KARS1 GALC FA2H ARSA
36 gangliosidosis 30.8 PSAP GALC ARSA
37 gm1 gangliosidosis 30.8 PSAP GALC ARSA
38 tay-sachs disease 30.6 PSAP GALC ARSA
39 cerebral palsy 30.6 TUBB4A PLP1 GFAP CNP ARSA
40 sandhoff disease 30.5 PSAP GALC ARSA
41 combined saposin deficiency 30.4 PSAP GALC EIF2B5 EIF2B3 EIF2B2 ARSA
42 niemann-pick disease 30.4 PSAP PLP1 GALC CNP ARSA
43 gaucher disease, type iii 30.4 PSAP ARSA
44 megalencephalic leukoencephalopathy with subcortical cysts 2a 30.3 TUBB4A PLP1
45 charcot-marie-tooth disease 30.3 SOX10 POLR3B PLP1 LMNB1 KARS1 AIFM1
46 gm2-gangliosidosis, ab variant 29.9 PSAP GALC
47 polr3-related leukodystrophy 11.8
48 metachromatic leukodystrophy due to saposin b deficiency 11.6
49 leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism 11.5
50 vasculopathy, retinal, with cerebral leukoencephalopathy and systemic manifestations 11.5

Comorbidity relations with Leukodystrophy via Phenotypic Disease Network (PDN):


Acute Cystitis Parkinson Disease, Late-Onset

Graphical network of the top 20 diseases related to Leukodystrophy:



Diseases related to Leukodystrophy

Symptoms & Phenotypes for Leukodystrophy

UMLS symptoms related to Leukodystrophy:


tremor; back pain; headache; syncope; pain; chronic pain; sciatica; seizures; vertigo/dizziness; sleeplessness

GenomeRNAi Phenotypes related to Leukodystrophy according to GeneCards Suite gene sharing:

25 (show all 19)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 no effect GR00402-S-1 10.1 AIFM1 ARSA CNP DEGS1 EIF2B2 EIF2B3
2 no effect GR00402-S-2 10.1 AIFM1 CNP EIF2B2 FA2H GALC LSM7
3 Increased shRNA abundance (Z-score > 2) GR00366-A-10 10.09 TUBB4A
4 Increased shRNA abundance (Z-score > 2) GR00366-A-104 10.09 EIF2B2
5 Increased shRNA abundance (Z-score > 2) GR00366-A-109 10.09 EIF2B2
6 Increased shRNA abundance (Z-score > 2) GR00366-A-12 10.09 EIF2B2
7 Increased shRNA abundance (Z-score > 2) GR00366-A-120 10.09 EIF2B2 EIF2B5
8 Increased shRNA abundance (Z-score > 2) GR00366-A-124 10.09 EIF2B5
9 Increased shRNA abundance (Z-score > 2) GR00366-A-135 10.09 TUBB4A
10 Increased shRNA abundance (Z-score > 2) GR00366-A-145 10.09 EIF2B5
11 Increased shRNA abundance (Z-score > 2) GR00366-A-147 10.09 EIF2B5
12 Increased shRNA abundance (Z-score > 2) GR00366-A-185 10.09 TUBB4A
13 Increased shRNA abundance (Z-score > 2) GR00366-A-20 10.09 EIF2B2
14 Increased shRNA abundance (Z-score > 2) GR00366-A-202 10.09 EIF2B2
15 Increased shRNA abundance (Z-score > 2) GR00366-A-26 10.09 TUBB4A
16 Increased shRNA abundance (Z-score > 2) GR00366-A-33 10.09 EIF2B5
17 Increased shRNA abundance (Z-score > 2) GR00366-A-69 10.09 EIF2B2
18 Increased shRNA abundance (Z-score > 2) GR00366-A-76 10.09 EIF2B2
19 Reduced mammosphere formation GR00396-S 9.5 AIFM1 EIF2B2 EIF2B5 GALC KARS1 PLP1

MGI Mouse Phenotypes related to Leukodystrophy:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 nervous system MP:0003631 10.22 AIFM1 ARSA CNP EIF2B5 FA2H GALC
2 homeostasis/metabolism MP:0005376 10.2 AIFM1 ARSA CNP DEGS1 EIF2B5 FA2H
3 muscle MP:0005369 10.07 AIFM1 CNP DEGS1 GALC GFAP LMNB1
4 cellular MP:0005384 10.03 AIFM1 ARSA CNP DEGS1 GALC GFAP
5 behavior/neurological MP:0005386 10.03 AIFM1 ARSA CNP DEGS1 EIF2B5 FA2H
6 vision/eye MP:0005391 9.65 AIFM1 ARSA CNP EIF2B5 FA2H GALC
7 mortality/aging MP:0010768 9.5 AIFM1 CNP DEGS1 EIF2B2 EIF2B3 EIF2B5

Drugs & Therapeutics for Leukodystrophy

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

(show all 50)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Prednisolone phosphate Approved, Vet_approved Phase 2, Phase 3 302-25-0
2
Prednisolone acetate Approved, Vet_approved Phase 2, Phase 3 52-21-1
3
Prednisolone Approved, Vet_approved Phase 2, Phase 3 50-24-8 4894 5755
4
Methylprednisolone hemisuccinate Approved Phase 2, Phase 3 2921-57-5 1875
5
Methylprednisolone Approved, Vet_approved Phase 2, Phase 3 83-43-2 4159 6741
6
Prednisolone hemisuccinate Experimental Phase 2, Phase 3 2920-86-7 4897
7
Methylprednisolone Acetate Phase 2, Phase 3 584547
8
Melphalan Approved Phase 2 148-82-3 4053 460612
9
Benzocaine Approved, Investigational Phase 2 1994-09-7, 94-09-7 2337
10
Hydroxyurea Approved Phase 2 127-07-1 3657
11
Tannic acid Approved Phase 2 1401-55-4 16129878 16129778
12
Clofarabine Approved, Investigational Phase 2 123318-82-1 119182
13
Coenzyme M Approved, Investigational Phase 2 3375-50-6 598 23662354
14
Mycophenolic acid Approved, Investigational Phase 2 24280-93-1 446541
15
Rituximab Approved Phase 2 174722-31-7
16
Fludarabine Approved Phase 2 75607-67-9, 21679-14-1 30751 657237
17
Celecoxib Approved, Investigational Phase 2 169590-42-5 2662
18
Acetylcysteine Approved, Investigational Phase 2 616-91-1 581 12035
19
Thiotepa Approved, Investigational Phase 2 52-24-4 5453
20
Tocopherol Approved, Investigational Phase 2 1406-66-2
21
Alemtuzumab Approved, Investigational Phase 2 216503-57-0
22
Busulfan Approved, Investigational Phase 2 55-98-1 2478
23
Cyclophosphamide Approved, Investigational Phase 2 50-18-0, 6055-19-2 2907
24
DL-alpha-Tocopherol Approved, Experimental, Investigational, Nutraceutical, Vet_approved Phase 2 59-02-9, 10191-41-0 2116 14985
25
Lipoic acid Approved, Investigational, Nutraceutical Phase 2 1200-22-2 864 6112
26
Tocotrienol Investigational Phase 2 6829-55-6 9929901
27 Calcineurin Inhibitors Phase 2
28 Cyclosporins Phase 2
29 Antimetabolites Phase 2
30 Dermatologic Agents Phase 2
31 Anti-Bacterial Agents Phase 2
32 Antitubercular Agents Phase 2
33 Antibiotics, Antitubercular Phase 2
34 Antilymphocyte Serum Phase 2
35 Vitamins Phase 2
36 Alpha-lipoic Acid Phase 2
37 N-monoacetylcystine Phase 2
38 Tocotrienols Phase 2
39 Tocopherols Phase 2
40 Antirheumatic Agents Phase 2
41 Alkylating Agents Phase 2
42 Antineoplastic Agents, Alkylating Phase 2
43 Antineoplastic Agents, Immunological Phase 2
44 Immunosuppressive Agents Phase 2
45 Immunologic Factors Phase 2
46
Aclarubicin Investigational Phase 1 57576-44-0
47 Adjuvants, Immunologic Phase 1
48 Aclacinomycins Phase 1
49
Warfarin Approved 81-81-2, 129-06-6 54678486
50 Anticoagulants

Interventional clinical trials:

(show top 50) (show all 54)
# 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 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
4 Allogeneic Hematopoietic Stem Cell Transplantation for Standard Risk Inherited Metabolic Disorders Completed NCT01043640 Phase 2 Campath-1H;Cyclophosphamide;Busulfan;Cyclosporine A;Mycophenolate Mofetil
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 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)
9 A Phase 1/2 Open-Label, Multicenter Dose-Ranging and Confirmatory Study to Assess the Safety, Tolerability and Efficacy of PBKR03 Administered to Pediatric Subjects With Early Infantile Krabbe Disease (Globoid Cell Leukodystrophy) Recruiting NCT04771416 Phase 1, Phase 2
10 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
11 A Phase 1/2 Clinical Study of Intravenous Gene Transfer With an AAVrh10 Vector Expressing GALC in Krabbe Subjects Receiving Hematopoietic Stem Cell Transplantation (RESKUE) Recruiting NCT04693598 Phase 1, 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 A Global, Multicenter, Open-label, Matched Historical Control Study of Intrathecal SHP611 in Subjects With Late Infantile Metachromatic Leukodystrophy Active, not recruiting NCT03771898 Phase 2 SHP611
14 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
15 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
16 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
17 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. Active, not recruiting NCT01801709 Phase 1, Phase 2
18 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
19 Treatment of Lysosomal and Peroxisomal Inborn Errors of Metabolism by Hematopoietic Cell Transplantation Terminated NCT00668564 Phase 2 Cyclophosphamide;Campath-1H;Busulfan
20 Evaluation of the Tolerance and Efficiency of a Combined Oral Therapy With Lithium and GTA in Patients With Canavan Disease Withdrawn NCT00657748 Phase 2 Lithium Gluconate (drug) Glyceryl Triacetate GTA (drug)
21 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 Completed NCT01586455 Phase 1 Human Placental Derived Stem Cell
22 A Pilot Study of Aclarubicin for the Treatment of Retinal Vasculopathy With Cerebral Leukodystrophy (RVCL) Completed NCT02723448 Phase 1 aclarubicin
23 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
24 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
25 Study of Pulmonary Complications in Pediatric Patients With Storage Disorders Undergoing Allogeneic Hematopoietic Stem Cell Transplantation Unknown status NCT00005900
26 Gene Therapy for Metachromatic Leukodystrophy (MLD) Using a Self-inactivating Lentiviral Vector (TYF-ARSA) Unknown status NCT03725670
27 Effect of Warfarin in the Treatment of Metachromatic Leukodystrophy Completed NCT00683189 Warfarin
28 A Longitudinal Observational Study That Will Evaluate Prospectively Clinical and Surrogate Parameters That Are Affected in Infant Patients With Globoid Cell Leukodystrophy Completed NCT00983879
29 Study of the Natural History of Cerebral White Matter Involvement in Metachromatic Leukodystrophy, Using High-field MRI and Diffusion Tensor Imaging Completed NCT01325025
30 Diagnostic and Screening Study of Genetic Disorders Completed NCT00006057
31 Stem Cell Transplantation (SCT) for Genetic Diseases Completed NCT00004378
32 Leukodystrophies of Unknown Cause Completed NCT00889174
33 Lysosomal Storage Disease: Health, Development, and Functional Outcome Surveillance in Preschool Children Completed NCT01938014
34 The Etiology, Pathogenesis, and Natural History of the Leukodystrophies Completed NCT02843555
35 The Nosology and Etiology of Leukodystrophies of Unknown Cause Completed NCT00001671
36 The Myelin Disorders Biorepository Project and Global Leukodystrophy Initiative Clinical Trials Network Recruiting NCT03047369
37 MATRIX - "Modeling Macrophages Activation Pattern in X-linked Adrenoleukodystrophy, Metachromatic Leukodystrophy and Adult Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia" Recruiting NCT04925349
38 A Systems-based Approach to Patient-focused Rare Disease Research and Product Development Recruiting NCT04628364
39 LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies Recruiting NCT02699190
40 Natural History, Diagnosis, and Outcomes for Leukodystrophies Recruiting NCT03639285
41 Coordination of Rare Diseases at Sanford Recruiting NCT01793168
42 Study of Adapted Exercise and Mindfulness Interventions to Improve Motor Function and Sleep Quality in Individuals With Neurodegenerative Disease Recruiting NCT05443906
43 The Institute for Myelin and Glia Exploration's Clinical Database of Patients With Krabbe Disease, A World-Wide Registry Recruiting NCT02993796
44 The Natural History of Metachromatic Leukodystrophy Active, not recruiting NCT00639132
45 Biomarker for Metachromatic Leukodystrophy Disease AN INTERNATIONAL, MULTICENTER, EPIDEMIOLOGICAL PROTOCOL Active, not recruiting NCT01536327
46 Diffusion Tensor Imaging (DTI) as a Tool to Identify Infants With Krabbe Disease in Urgent Need of Treatment Active, not recruiting NCT00787865
47 Biomarker for Krabbe Disease AN INTERNATIONAL, MULTICENTER, EPIDEMIOLOGI-CAL PROTOCOL Active, not recruiting NCT01425489
48 ScreenPlus: A Comprehensive, Flexible, Multi-disorder Newborn Screening Program Enrolling by invitation NCT05368038
49 Characterization and Outcome of Children With Leukodystrophy: An Observational Study at Sohag University Hospital Not yet recruiting NCT04781010
50 Single Patient Expanded Access Protocol: Phase I/II Pilot Study of Mixed Chimerism to Treat Inherited Metabolic Disorders No longer available NCT02021266

Search NIH Clinical Center for Leukodystrophy

Genetic Tests for Leukodystrophy

Genetic tests related to Leukodystrophy:

# Genetic test Affiliating Genes
1 Leukodystrophy 28

Anatomical Context for Leukodystrophy

Organs/tissues related to Leukodystrophy:

MalaCards : Spinal Cord, Bone Marrow, Brain, Bone, T Cells, Skin, Adrenal Cortex

Publications for Leukodystrophy

Articles related to Leukodystrophy:

(show top 50) (show all 3582)
# Title Authors PMID Year
1
Progressive Early-Onset Leukodystrophy Related to Biallelic Variants in the KARS Gene: The First Case Described in Latin America. 62 5
33260297 2020
2
DEGS1 variant causes neurological disorder. 62 5
31186544 2019
3
Predicting clinical phenotypes of metachromatic leukodystrophy based on the arylsulfatase A activity and the ARSA genotype? - Chances and challenges. 62 41
36240581 2022
4
The importance of early diagnosis and views on newborn screening in metachromatic leukodystrophy: results of a Caregiver Survey in the UK and Republic of Ireland. 62 41
36329444 2022
5
Understanding caregiver descriptions of initial signs and symptoms to improve diagnosis of metachromatic leukodystrophy. 62 41
36195888 2022
6
Whole-genome sequencing of patients with rare diseases in a national health system. 5
32581362 2020
7
SOX10 structure-function analysis in the chicken neural tube reveals important insights into its role in human neurocristopathies. 53 62
20308050 2010
8
Mutation of FA2H underlies a complicated form of hereditary spastic paraplegia (SPG35). 53 62
20104589 2010
9
A family with autosomal dominant leukodystrophy linked to 5q23.2-q23.3 without lamin B1 mutations. 53 62
19961535 2010
10
Fatty acid 2-Hydroxylation in mammalian sphingolipid biology. 53 62
20026285 2010
11
MLC1 trafficking and membrane expression in astrocytes: role of caveolin-1 and phosphorylation. 53 62
19931615 2010
12
Peptidomics analysis of lymphoblastoid cell lines. 53 62
20013214 2010
13
Eukaryotic initiation factor 2B (eIF2B) GEF activity as a diagnostic tool for EIF2B-related disorders. 53 62
20016818 2009
14
SURF-1 gene mutation associated with leukoencephalopathy in a 2-year-old. 53 62
19805825 2009
15
Neuronal loss in Pelizaeus-Merzbacher disease differs in various mutations of the proteolipid protein 1. 53 62
19562355 2009
16
Pathogenesis of leukodystrophy for Krabbe disease: molecular mechanism and clinical treatment. 53 62
19332366 2009
17
miR-23 regulation of lamin B1 is crucial for oligodendrocyte development and myelination. 53 62
19259393 2009
18
The ovarioleukodystrophy. 53 62
18678442 2008
19
Molecular pathogenesis of megalencephalic leukoencephalopathy with subcortical cysts: mutations in MLC1 cause folding defects. 53 62
18757878 2008
20
Mutations in the fatty acid 2-hydroxylase gene are associated with leukodystrophy with spastic paraparesis and dystonia. 53 62
19068277 2008
21
Nur7 is a nonsense mutation in the mouse aspartoacylase gene that causes spongy degeneration of the CNS. 53 62
18987190 2008
22
PLP1 splicing abnormalities identified in Pelizaeus-Merzbacher disease and SPG2 fibroblasts are associated with different types of mutations. 53 62
18470932 2008
23
Hearing profile and MRI myelination of auditory pathway in Pelizaeus-Merzbacher disease. 53 62
18421608 2008
24
Identification of proteolipid protein 1 gene duplication by multiplex ligation-dependent probe amplification: first report of genetically confirmed family of Pelizaeus-Merzbacher disease in Korea. 53 62
18437021 2008
25
Genetic and clinical heterogeneity in eIF2B-related disorder. 53 62
18263758 2008
26
Deletions at the SOX10 gene locus cause Waardenburg syndrome types 2 and 4. 53 62
17999358 2007
27
Translation of SOX10 3' untranslated region causes a complex severe neurocristopathy by generation of a deleterious functional domain. 53 62
17855451 2007
28
"Laminopathies": a wide spectrum of human diseases. 53 62
17467691 2007
29
N-Acetylaspartate in the CNS: from neurodiagnostics to neurobiology. 53 62
17275978 2007
30
Synergistic effects of the SAPK/JNK and the proteasome pathway on glial fibrillary acidic protein (GFAP) accumulation in Alexander disease. 53 62
17038307 2006
31
Alexander disease-associated glial fibrillary acidic protein mutations in mice induce Rosenthal fiber formation and a white matter stress response. 53 62
17065456 2006
32
Lamin B1 duplications cause autosomal dominant leukodystrophy. 53 62
16951681 2006
33
Aberrant trafficking of a proteolipid protein in a mild Pelizaeus-Merzbacher disease. 53 62
16844304 2006
34
Natural history of Canavan disease revealed by proton magnetic resonance spectroscopy (1H-MRS) and diffusion-weighted MRI. 53 62
17177147 2006
35
Childhood ataxia with CNS hypomyelination/vanishing white matter disease--a common leukodystrophy caused by abnormal control of protein synthesis. 53 62
16378743 2006
36
PLP1 and GPM6B intragenic copy number analysis by MAPH in 262 patients with hypomyelinating leukodystrophies: Identification of one partial triplication and two partial deletions of PLP1. 53 62
16416265 2006
37
Shah-Waardenburg syndrome and PCWH associated with SOX10 mutations: a case report and review of the literature. 53 62
16504559 2006
38
Heightened stress response in primary fibroblasts expressing mutant eIF2B genes from CACH/VWM leukodystrophy patients. 53 62
16041584 2005
39
Atypical MRI findings in Canavan disease: a patient with a mild course. 53 62
16217711 2005
40
Disorders of nuclear-mitochondrial intergenomic signaling. 53 62
15921863 2005
41
EIF2B5 mutations compromise GFAP+ astrocyte generation in vanishing white matter leukodystrophy. 53 62
15723074 2005
42
Dominantly-inherited adult-onset leukodystrophy with palatal tremor caused by a mutation in the glial fibrillary acidic protein gene. 53 62
15390001 2004
43
Decreased guanine nucleotide exchange factor activity in eIF2B-mutated patients. 53 62
15054402 2004
44
The effect of genotype on the natural history of eIF2B-related leukodystrophies. 53 62
15136673 2004
45
Alexander disease: a leukodystrophy caused by a mutation in GFAP. 53 62
15139294 2004
46
The latest on leukodystrophies. 53 62
15021247 2004
47
Indian Agarwal megalencephalic leukodystrophy with cysts is caused by a common MLC1 mutation. 53 62
15037685 2004
48
Globoid cell leukodystrophy (Krabbe's disease): update. 53 62
14572137 2003
49
Canavan disease: a monogenic trait with complex genomic interaction. 53 62
14567959 2003
50
Membrane phospholipids and high-energy metabolites in childhood ataxia with CNS hypomyelination. 53 62
12963756 2003

Variations for Leukodystrophy

ClinVar genetic disease variations for Leukodystrophy:

5 (show all 18)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TMEM63A NM_014698.3(TMEM63A):c.503G>A (p.Gly168Glu) SNV Pathogenic
689459 rs1576101665 GRCh37: 1:226055599-226055599
GRCh38: 1:225867899-225867899
2 TMEM63A NM_014698.3(TMEM63A):c.1385T>A (p.Ile462Asn) SNV Pathogenic
689460 rs1576080546 GRCh37: 1:226044710-226044710
GRCh38: 1:225857010-225857010
3 TMEM63A NM_014698.3(TMEM63A):c.1699G>A (p.Gly567Ser) SNV Pathogenic
689461 rs1576074651 GRCh37: 1:226041428-226041428
GRCh38: 1:225853727-225853727
4 KARS1 NM_005548.3(KARS1):c.1493C>T (p.Ala498Val) SNV Pathogenic
Uncertain Significance
694746 rs1415687857 GRCh37: 16:75663371-75663371
GRCh38: 16:75629473-75629473
5 LSM7 NM_016199.3(LSM7):c.121G>A (p.Asp41Asn) SNV Pathogenic
996070 GRCh37: 19:2324172-2324172
GRCh38: 19:2324173-2324173
6 EIF2B5 NM_003907.3(EIF2B5):c.943C>T (p.Arg315Cys) SNV Pathogenic
598970 rs113994063 GRCh37: 3:183858305-183858305
GRCh38: 3:184140517-184140517
7 ARSA NM_000487.6(ARSA):c.1010A>T (p.Asp337Val) SNV Pathogenic
3080 rs74315475 GRCh37: 22:51064461-51064461
GRCh38: 22:50626033-50626033
8 DEGS1 NM_003676.4(DEGS1):c.764A>G (p.Asn255Ser) SNV Pathogenic
625852 rs768180196 GRCh37: 1:224377960-224377960
GRCh38: 1:224190258-224190258
9 RAB33A, AIFM1 NM_004208.4(AIFM1):c.1646C>T (p.Ala549Val) SNV Likely Pathogenic
373913 rs761953453 GRCh37: X:129264069-129264069
GRCh38: X:130130094-130130094
10 HEXA NM_000520.6(HEXA):c.1305C>T (p.Tyr435=) SNV Likely Pathogenic
100729 rs587779406 GRCh37: 15:72638893-72638893
GRCh38: 15:72346552-72346552
11 RNF216 NM_207111.4(RNF216):c.2061G>A (p.Lys687=) SNV Likely Pathogenic
183356 rs730882248 GRCh37: 7:5751392-5751392
GRCh38: 7:5711761-5711761
12 ALMS1 NM_001378454.1(ALMS1):c.1732del (p.Arg578fs) DEL Likely Pathogenic
374506 rs777476179 GRCh37: 2:73675386-73675386
GRCh38: 2:73448259-73448259
13 GALC NM_000153.4(GALC):c.196G>A (p.Ala66Thr) SNV Likely Pathogenic
374023 rs1057518843 GRCh37: 14:88454867-88454867
GRCh38: 14:87988523-87988523
14 GALC NM_000153.4(GALC):c.850G>A (p.Gly284Ser) SNV Likely Pathogenic
374024 rs377274761 GRCh37: 14:88434737-88434737
GRCh38: 14:87968393-87968393
15 overlap with 8 genes GRCh37/hg19 6p24.1-23(chr6:12536624-13968949) CN GAIN Uncertain Significance
523282 GRCh37: 6:12536624-13968949
GRCh38:
16 SLC9A6 NM_001379110.1(SLC9A6):c.1190C>A (p.Ala397Glu) SNV Uncertain Significance
523398 rs1556619324 GRCh37: X:135098913-135098913
GRCh38: X:136016754-136016754
17 PEX6 NM_000287.4(PEX6):c.1680C>G (p.Pro560=) SNV Uncertain Significance
1683500 GRCh37: 6:42936036-42936036
GRCh38: 6:42968298-42968298
18 MEN1 NM_001370259.2(MEN1):c.1618C>T (p.Pro540Ser) SNV Uncertain Significance
200987 rs745404679 GRCh37: 11:64572021-64572021
GRCh38: 11:64804549-64804549

Copy number variations for Leukodystrophy from CNVD:

6
# CNVD ID Chromosome Start End Type Gene Symbol CNVD Disease
1 88184 14 87469110 87529660 Insertion GALC leukodystrophy

Expression for Leukodystrophy

Search GEO for disease gene expression data for Leukodystrophy.

Pathways for Leukodystrophy

GO Terms for Leukodystrophy

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

# Name GO ID Score Top Affiliating Genes
1 lysosome GO:0005764 9.7 TMEM63A TMEM106B PSAP GFAP GALC ARSA
2 myelin sheath GO:0043209 9.55 TUBB4A PLP1 CNP
3 eukaryotic translation initiation factor 2B complex GO:0005851 9.1 EIF2B5 EIF2B3 EIF2B2

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

# Name GO ID Score Top Affiliating Genes
1 response to glucose GO:0009749 9.91 EIF2B5 EIF2B3 EIF2B2
2 translational initiation GO:0006413 9.88 EIF2B5 EIF2B3 EIF2B2
3 response to peptide hormone GO:0043434 9.85 EIF2B5 EIF2B3 EIF2B2
4 response to heat GO:0009408 9.8 EIF2B5 EIF2B3 EIF2B2
5 astrocyte development GO:0014002 9.63 PLP1 GFAP EIF2B5
6 sphingolipid metabolic process GO:0006665 9.56 FA2H GALC PSAP
7 myelination GO:0042552 9.5 PLP1 GALC EIF2B5 EIF2B2
8 oligodendrocyte development GO:0014003 9.23 SOX10 EIF2B5 EIF2B3 EIF2B2

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

# Name GO ID Score Top Affiliating Genes
1 translation initiation factor activity GO:0003743 9.1 EIF2B5 EIF2B3 EIF2B2

Sources for Leukodystrophy

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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