MCID: KRB001
MIFTS: 70

Krabbe Disease

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

Aliases & Classifications for Krabbe Disease

MalaCards integrated aliases for Krabbe Disease:

Name: Krabbe Disease 53 37 12 72 23 49 24 50 55 71 36 13 51 14
Globoid Cell Leukodystrophy 53 12 23 49 50 55 69
Galc Deficiency 53 23 49 24 55 71
Galactosylceramide Beta-Galactosidase Deficiency 53 12 49 71 28
Globoid Cell Leukoencephalopathy 53 12 49 71
Galactocerebrosidase Deficiency 53 23 49 55
Gld 53 49 24 71
Leukodystrophy, Globoid Cell 72 71 41
Gcl 49 24 71
Galactosylceramidase Deficiency 23 55
Diffuse Globoid Body Sclerosis 12 24
Krabbe Leukodystrophy 72 49
Galactosylceramidase Deficiency Disease 24
Globoid Cell Leukodystrophy; Gld; Gcl 53
Infantile Globoid Cell Leukodystrophy 69
Beta Galactocerebrosidase Deficiency 12
Galactosylcerebrosidase Deficiency 24
Galactosylsphingosine Lipidosis 24
Galactosylceramide Lipidosis 24
Krabbe's Leukodystrophy 12
Psychosine Lipidosis 24
Krabbe's Disease 12

Characteristics:

Orphanet epidemiological data:

55
krabbe disease
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (United States),1-9/100000 (Europe),1-9/1000000 (Worldwide),1-9/1000000 (France),1-9/100000 (Sweden); Age of onset: Adolescent,Adult,Childhood,Infancy,Neonatal; Age of death: any age;

OMIM:

53
Miscellaneous:
episodic fever
four clinical forms of krabbe disease
infantile form has onset within first 6 months of life
infantile form accounts for 90% of cases
infantile form usually leads to death by age 2 years
late infantile form has onset between 19 months and 4 years
juvenile form has onset between 4 and 19 years
adult form onset has after 20 years
incidence of 1 in 100,000

Inheritance:
autosomal recessive


HPO:

31
krabbe disease:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Krabbe Disease

NIH Rare Diseases : 49 Krabbe disease is an inherited condition that affects the nervous system. The signs and symptoms of the condition and the disease severity differ by type. Babies affected by early-onset (infantile) Krabbe disease, the most common and severe form of the condition, typically develop features in the first six months of life. Symptoms of infantile Krabbe disease may include irritability; failure to thrive; slowed development; unexplained fevers; and progressive muscle weakness, hearing loss and vision loss. People affected by the late-onset forms may not develop symptoms until later in childhood, early adolescence or even into adulthood. Signs and symptoms of these forms are extremely variable but may include muscle weakness and rigidity; walking difficulties; vision loss; intellectual regression; and/or seizures. Krabbe disease is caused by changes (mutations) in the GALC gene and is inherited in an autosomal recessive manner. Treatment is generally based on the signs and symptoms present in each person; however, preliminary studies suggest that it may be beneficial to use hematopoietic stem cell transplantation (i.e. umbilical cord blood stem cells) as a treatment for patients in the early stages of infantile Krabbe disease and older people with mild symptoms. Last updated: 10/9/2015

MalaCards based summary : Krabbe Disease, also known as globoid cell leukodystrophy, is related to infantile krabbe disease and sphingolipidosis, and has symptoms including ataxia, fever and seizures. An important gene associated with Krabbe Disease is GALC (Galactosylceramidase), and among its related pathways/superpathways are Sphingolipid metabolism and Lysosome. The drugs Cyclophosphamide and Busulfan have been mentioned in the context of this disorder. Affiliated tissues include brain, bone and eye, and related phenotypes are behavior/neurological and hematopoietic system

OMIM : 53 Krabbe disease is an autosomal recessive lysosomal disorder affecting the white matter of the central and peripheral nervous systems. Most patients present within the first 6 months of life with 'infantile' or 'classic' disease manifest as extreme irritability, spasticity, and developmental delay (Wenger et al., 2000). There is severe motor and mental deterioration, leading to decerebration and death by age 2 years. Approximately 10 to 15% of patients have a later onset, commonly differentiated as late-infantile (6 months to 3 years), juvenile (3 to 8 years), and even adult-onset forms. The later-onset forms have less disease severity and slower progression. These later-onset patients can be clinically normal until weakness, vision loss and intellectual regression become evident; those with adult onset may have spastic paraparesis as the only symptom. Disease severity is variable, even within families (summary by Tappino et al., 2010). (245200)

UniProtKB/Swiss-Prot : 71 Leukodystrophy, globoid cell: An autosomal recessive disorder characterized by insufficient catabolism of several galactolipids that are important for normal myelin production. Four clinical forms are recognized. The infantile form accounts for 90% of cases. It manifests before six months of age with irritability, spasticity, arrest of motor and mental development, and bouts of temperature elevation without infection. This is followed by myoclonic jerks of arms and legs, oposthotonus, hypertonic fits, and mental regression, which progresses to a severe decerebrate condition with no voluntary movements and death from respiratory infections or cerebral hyperpyrexia before 2 years of age. Cases with later onset present with unexplained blindness, weakness and sensorimotor peripheral neuropathy, mental deterioration and death.

NINDS : 50 Krabbe disease is a rare, inherited metabolic disorder in which harmful amounts of lipids (fatty materials such as oils and waxes) build up in various cells and tissues in the body and destroys brain cells.  Krabbe disease, also known as globoid cell leukodystrophy, is characterized by the presence of globoid cells (cells that have more than one nucleus) that break down  the nerve’s protective myelin coating. Krabbe disease is caused by a deficiency of galactocerebrosidase, an essential enzyme for myelin metabolism.  The disease most often affects infants, with onset before age 6 months, but can occur in adolescence or adulthood.  Symptoms include severe deterioration of mental and motor skills, muscle weakness, hypertonia (inability of a muscle to stretch), myoclonic seizures (sudden, shock-like contractions of the limbs), and spasticity (involuntary and awkward movement). Other symptoms may include irritability, unexplained fever, blindness, difficulty with swallowing, and deafness. 

Genetics Home Reference : 24 Krabbe disease (also called globoid cell leukodystrophy) is a severe neurological condition. It is part of a group of disorders known as leukodystrophies, which result from the loss of myelin (demyelination) in the nervous system. Myelin is the protective covering around nerve cells that ensures the rapid transmission of nerve signals. Krabbe disease is also characterized by abnormal cells in the brain called globoid cells, which are large cells that usually have more than one nucleus.

GeneReviews: NBK1238

Related Diseases for Krabbe Disease

Diseases in the Krabbe Disease family:

Infantile Krabbe Disease Late-Infantile/juvenile Krabbe Disease
Adult Krabbe Disease

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

(show top 50) (show all 55)
# Related Disease Score Top Affiliating Genes
1 infantile krabbe disease 33.8 GALC PSAP
2 sphingolipidosis 31.0 ARSA GALC PSAP
3 leukodystrophy 30.3 ARSA GALC PSAP
4 metachromatic leukodystrophy 29.7 ARSA GALC PSAP
5 nervous system disease 29.2 CASP3 MBP NOS2
6 krabbe disease, atypical, due to saposin a deficiency 12.4
7 adult krabbe disease 12.1
8 late-infantile/juvenile krabbe disease 12.0
9 lymphedema, hereditary, iii 11.0
10 congenital generalized lipodystrophy 10.9
11 sturge-weber syndrome 10.9
12 cerebral atrophy 10.9
13 spasticity 10.9
14 gaucher disease, type i 10.3 CHIT1 PSAP
15 endotheliitis 10.1
16 niemann-pick disease, type a 10.1 CHIT1 MBP
17 internal hemorrhoid 10.1 CASP3 NOS2
18 mycetoma 10.1 CHIT1 NOS2
19 occlusion precerebral artery 10.1 CASP3 MBP
20 neuronitis 10.0
21 neuropathy 10.0
22 traumatic brain injury 10.0 CASP3 MBP
23 spinocerebellar degeneration 10.0
24 metachromatic leukodystrophy, adult form 10.0 ARSA PSAP
25 metachromatic leukodystrophy, late infantile form 10.0 ARSA PSAP
26 metachromatic leukodystrophy, juvenile form 10.0 ARSA PSAP
27 brain injury 9.9 CASP3 MBP
28 inclusion-cell disease 9.9 ARSA PSAP
29 periventricular leukomalacia 9.9 MBP NOS2
30 multiple sclerosis 9.9
31 aging 9.9
32 hematopoietic stem cell transplantation 9.9
33 cerebritis 9.9
34 leukomalacia 9.9 MBP NOS2
35 spinal cord injury 9.9 CASP3 NOS2 PLA2G2A
36 varicocele 9.8 CASP3 NOS2
37 lipid storage disease 9.7 ARSA GALC PSAP
38 intussusception 9.7
39 carney complex, type 1 9.7
40 ceroid lipofuscinosis, neuronal, 1 9.7
41 adrenoleukodystrophy 9.7
42 rett syndrome 9.7
43 ataxia and polyneuropathy, adult-onset 9.7
44 aceruloplasminemia 9.7
45 ataxia-oculomotor apraxia 3 9.7
46 lysosomal storage disease 9.7
47 motor neuron disease 9.7
48 neuronal ceroid lipofuscinosis 9.7
49 peripheral nervous system disease 9.7
50 conjunctivitis 9.7

Graphical network of the top 20 diseases related to Krabbe Disease:



Diseases related to Krabbe Disease

Symptoms & Phenotypes for Krabbe Disease

Symptoms via clinical synopsis from OMIM:

53
Neurologic Central Nervous System:
seizures
hyperirritability
hydrocephalus
developmental regression
motor deterioration
more
Head And Neck Eyes:
nystagmus
optic atrophy
blindness
abnormal flash visual evoked potentials (vep)

Head And Neck Ears:
deafness
abnormal brainstem auditory evoked potentials (baep)

Laboratory Abnormalities:
elevated cerebrospinal fluid (csf) protein
galactocerebroside beta-galactosidase deficiency in serum, leukocytes, and fibroblasts

Abdomen Gastroin testinal:
vomiting

Growth Other:
failure to thrive

Neurologic Peripheral Nervous System:
sensorimotor peripheral neuropathy
diffuse demyelinating neuropathy
decreased nerve conduction velocities


Clinical features from OMIM:

245200

Human phenotypes related to Krabbe Disease:

55 31 (show all 47)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ataxia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001251
2 fever 55 31 frequent (33%) Frequent (79-30%) HP:0001945
3 seizures 55 31 Frequent (79-30%) HP:0001250
4 spasticity 55 31 hallmark (90%) Very frequent (99-80%) HP:0001257
5 gait disturbance 55 31 frequent (33%) Frequent (79-30%) HP:0001288
6 hearing impairment 55 31 Very frequent (99-80%) HP:0000365
7 global developmental delay 55 31 hallmark (90%) Very frequent (99-80%) HP:0001263
8 recurrent respiratory infections 55 31 frequent (33%) Frequent (79-30%) HP:0002205
9 sensorineural hearing impairment 55 31 hallmark (90%) Very frequent (99-80%) HP:0000407
10 visual impairment 55 31 hallmark (90%) Very frequent (99-80%) HP:0000505
11 emg abnormality 55 31 hallmark (90%) Very frequent (99-80%) HP:0003457
12 irritability 55 31 frequent (33%) Frequent (79-30%) HP:0000737
13 sensory neuropathy 55 31 hallmark (90%) Very frequent (99-80%) HP:0000763
14 abnormality of the thumb 55 31 hallmark (90%) Very frequent (99-80%) HP:0001172
15 weight loss 55 31 occasional (7.5%) Occasional (29-5%) HP:0001824
16 generalized myoclonic seizures 55 31 frequent (33%) Frequent (79-30%) HP:0002123
17 cloverleaf skull 55 31 hallmark (90%) Very frequent (99-80%) HP:0002676
18 hemiplegia/hemiparesis 55 31 frequent (33%) Frequent (79-30%) HP:0004374
19 aplasia/hypoplasia of the abdominal wall musculature 55 31 hallmark (90%) Very frequent (99-80%) HP:0010318
20 feeding difficulties 55 31 hallmark (90%) Very frequent (99-80%) HP:0011968
21 vomiting 31 HP:0002013
22 hydrocephalus 31 HP:0000238
23 nystagmus 31 HP:0000639
24 muscular hypotonia 31 HP:0001252
25 failure to thrive 31 HP:0001508
26 eeg abnormality 31 HP:0002353
27 developmental regression 31 HP:0002376
28 behavioral abnormality 55 Very frequent (99-80%)
29 optic atrophy 31 HP:0000648
30 blindness 31 HP:0000618
31 hypertonia 31 HP:0001276
32 abnormality of metabolism/homeostasis 55 Very frequent (99-80%)
33 peripheral neuropathy 55 Very frequent (99-80%)
34 decreased nerve conduction velocity 31 HP:0000762
35 motor deterioration 31 HP:0002333
36 neurodegeneration 31 HP:0002180
37 progressive spasticity 31 HP:0002191
38 sensorimotor neuropathy 31 HP:0007141
39 increased csf protein 31 HP:0002922
40 autoimmune thrombocytopenia 31 HP:0001973
41 peripheral demyelination 31 HP:0011096
42 episodic fever 31 HP:0001954
43 hyperactive deep tendon reflexes 31 HP:0006801
44 diffuse cerebral atrophy 31 HP:0002506
45 cns demyelination 31 HP:0007305
46 decerebrate rigidity 31 HP:0025013
47 abnormal flash visual evoked potentials 31 HP:0007928

UMLS symptoms related to Krabbe Disease:


hyperirritability, vomiting, seizures

MGI Mouse Phenotypes related to Krabbe Disease:

43 (show all 11)
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.1 ARSA CASP3 GALC MBP NOS2 PLA2G4A
2 hematopoietic system MP:0005397 10.03 ARSA CASP3 GALC MBP NOS2 PLA2G4A
3 cellular MP:0005384 10.02 CASP3 GALC MBP NOS2 PLA2G4A PLA2G6
4 immune system MP:0005387 10.02 PSAP ARSA CASP3 CHIT1 GALC MBP
5 homeostasis/metabolism MP:0005376 10.01 ARSA CASP3 GALC MBP NOS2 PLA2G4A
6 nervous system MP:0003631 9.86 ARSA CASP3 GALC MBP NOS2 PLA2G4A
7 muscle MP:0005369 9.8 PLA2G4A PLA2G6 PSAP CASP3 GALC NOS2
8 hearing/vestibular/ear MP:0005377 9.76 ARSA CASP3 MBP PSAP
9 renal/urinary system MP:0005367 9.55 CASP3 GALC NOS2 PLA2G4A PSAP
10 reproductive system MP:0005389 9.43 CASP3 MBP NOS2 PLA2G4A PLA2G6 PSAP
11 vision/eye MP:0005391 9.1 CASP3 GALC MBP NOS2 PLA2G6 PSAP

Drugs & Therapeutics for Krabbe Disease

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

(show all 48)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Cyclophosphamide Approved, Investigational Phase 2, Phase 3 50-18-0, 6055-19-2 2907
2
Busulfan Approved, Investigational Phase 2, Phase 3 55-98-1 2478
3
Prednisolone Approved, Vet_approved Phase 2, Phase 3 50-24-8 5755
4
Methylprednisolone Approved, Vet_approved Phase 2, Phase 3 83-43-2 6741
5 Prednisolone acetate Phase 2, Phase 3
6 Alkylating Agents Phase 2, Phase 3
7 Methylprednisolone acetate Phase 2, Phase 3
8 Methylprednisolone Hemisuccinate Phase 2, Phase 3
9 Antilymphocyte Serum Phase 2, Phase 3
10 Prednisolone hemisuccinate Phase 2, Phase 3
11 Immunosuppressive Agents Phase 2, Phase 3
12 Prednisolone phosphate Phase 2, Phase 3
13 Antirheumatic Agents Phase 2, Phase 3
14
Melphalan Approved Phase 2 148-82-3 460612 4053
15
Mycophenolic acid Approved Phase 2 24280-93-1 446541
16
Mycophenolate mofetil Approved, Investigational Phase 2 128794-94-5 5281078
17
Hydroxyurea Approved Phase 2 127-07-1 3657
18
Miconazole Approved, Investigational, Vet_approved Phase 2 22916-47-8 4189
19
Mesna Approved, Investigational Phase 2 3375-50-6 598
20
alemtuzumab Approved, Investigational Phase 2 216503-57-0
21
Clofarabine Approved, Investigational Phase 2 123318-82-1 119182
22
Benzocaine Approved, Investigational Phase 2 1994-09-7, 94-09-7 2337
23
Celecoxib Approved, Investigational Phase 2 169590-42-5 2662
24
Fludarabine Approved Phase 2 21679-14-1, 75607-67-9 30751
25
rituximab Approved Phase 2 174722-31-7 10201696
26 Thiotepa Approved, Investigational Phase 2 52-24-4 5453
27
Acetylcysteine Approved, Investigational Phase 2 616-91-1 12035
28 tannic acid Approved, Nutraceutical Phase 2
29 Tocopherol Approved, Investigational, Nutraceutical Phase 2
30
Vitamin E Approved, Nutraceutical, Vet_approved Phase 2 59-02-9 14985
31 Cyclosporins Phase 2
32 Nucleic Acid Synthesis Inhibitors Phase 2
33 Dermatologic Agents Phase 2
34 Anti-Bacterial Agents Phase 2
35 Anti-Infective Agents Phase 2
36 Antifungal Agents Phase 2
37 Antimetabolites Phase 2
38 Antimetabolites, Antineoplastic Phase 2
39 Antibiotics, Antitubercular Phase 2
40 Calcineurin Inhibitors Phase 2
41 Antitubercular Agents Phase 2
42 N-monoacetylcystine Phase 2
43 Thioctic Acid Phase 2
44 Tocopherols Phase 2
45 Tocotrienols Phase 2
46 Vitamins Phase 2
47 Tocotrienol Investigational, Nutraceutical Phase 2 6829-55-6
48 Alpha-lipoic Acid Nutraceutical Phase 2

Interventional clinical trials:

(show all 22)

# Name Status NCT ID Phase Drugs
1 Stem Cell Transplant for Inborn Errors of Metabolism Completed NCT00176904 Phase 2, Phase 3 Busulfan, Cyclophosphamide, Antithymocyte Globulin
2 ALD-101 Adjuvant Therapy of Unrelated Umbilical Cord Blood Transfusion (UCBT) in Patients With Inherited Metabolic Diseases Terminated NCT00654433 Phase 3
3 HSCT for High Risk Inherited Inborn Errors Completed NCT00383448 Phase 2 Clofarabine;Melphalan;Alemtuzumab;mycophenylate mofetil;Hydroxyurea
4 Allogeneic Bone Marrow Transplant for Inherited Metabolic Disorders Completed NCT01043640 Phase 2 Campath-1H;Cyclophosphamide;Busulfan;Cyclosporine A;Mycophenolate Mofetil
5 MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis 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)
6 MGTA-456 in Patients With Inherited Metabolic Disorders Undergoing Hematopoietic Stem Cell Transplantation (HSCT) Recruiting NCT03406962 Phase 2 MGTA-456
7 Reduced Intensity Conditioning for Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT Recruiting NCT01962415 Phase 2 Hydroxyurea;Alemtuzumab;Fludarabine;Melphalan;Thiotepa
8 Phase I/II Pilot Study of Mixed Chimerism to Treat Inherited Metabolic Disorders Active, not recruiting NCT01372228 Phase 1, Phase 2
9 Hematopoietic Stem Cell Transplantation (HCT) for Inborn Errors of Metabolism Terminated NCT00668564 Phase 2 Cyclophosphamide;Campath-1H;Busulfan
10 UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells Recruiting NCT02254863 Phase 1
11 Human Placental-Derived Stem Cell Transplantation Active, not recruiting NCT01586455 Phase 1 Human Placental Derived Stem Cell
12 Lysosomal Storage Disease: Health, Development, and Functional Outcome Surveillance in Preschool Children Unknown status NCT01938014
13 Study of Pulmonary Complications in Pediatric Patients With Storage Disorders Undergoing Allogeneic Hematopoietic Stem Cell Transplantation Unknown status NCT00005900
14 The Natural History of Infantile Globoid Cell Leukodystrophy Completed NCT00983879
15 Diagnostic and Screening Study of Genetic Disorders Completed NCT00006057
16 Reduced-Intensity Hematopoietic Stem Cell Transplant for High Risk Lysosomal and Peroxisomal Disorders Completed NCT01626092 Campath-1H;Clofarabine;Melphalan;Cyclosporine A;Mycophenolate mofetil
17 Krabbe Disease Global Patient Registry Recruiting NCT02993796
18 Biomarker for Krabbe Disease Recruiting NCT01425489
19 Longitudinal Study of Neurodegenerative Disorders Recruiting NCT03333200
20 Genetic Characterization of Movement Disorders and Dementias Recruiting NCT02014246
21 Diffusion Tensor Imaging (DTI) in Infants With Krabbe Disease Active, not recruiting NCT00787865
22 An Observational Study of Pediatric Subjects With Globoid Cell Leukodystrophy (GLD) Withdrawn NCT01093105

Search NIH Clinical Center for Krabbe Disease

Cell-based therapeutics:


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

Cochrane evidence based reviews: leukodystrophy, globoid cell

Genetic Tests for Krabbe Disease

Genetic tests related to Krabbe Disease:

# Genetic test Affiliating Genes
1 Galactosylceramide Beta-Galactosidase Deficiency 28 GALC

Anatomical Context for Krabbe Disease

MalaCards organs/tissues related to Krabbe Disease:

38
Brain, Bone, Eye, Bone Marrow, Skin, Testes, Spinal Cord

Publications for Krabbe Disease

Articles related to Krabbe Disease:

(show top 50) (show all 245)
# Title Authors Year
1
AAVrh10 gene therapy ameliorates central and peripheral nervous system disease in canine globoid cell leukodystrophy (Krabbe disease). ( 29316812 )
2018
2
Consensus guidelines for newborn screening, diagnosis and treatment of infantile Krabbe disease. ( 29391017 )
2018
3
Quantitative DTI metrics in a canine model of Krabbe disease: comparisons versus age-matched controls across multiple ages. ( 29350082 )
2018
4
Large-scale Study of Clinical and Biochemical Characteristics of Chinese Patients Diagnosed with Krabbe Disease. ( 28598007 )
2017
5
Mesenchymal Stem Cells Yield Transient Improvements in Motor Function in an Infant Rhesus Macaque with Severe Early-Onset Krabbe Disease. ( 28170189 )
2017
6
Late onset Krabbe disease due to the new GALC p.Ala543Pro mutation, with intriguingly high residual GALC activity inA vitro. ( 28109651 )
2017
7
Stem cell transplantation in Krabbe disease: New truths discovered and opinions change. ( 28855407 )
2017
8
WITHDRAWN: Clinical and molecular analysis of six novel GALC mutations identified in 7 Chinese children with Krabbe disease. ( 28552323 )
2017
9
Lymphocyte Galactocerebrosidase Activity by LC-MS/MS for Post-Newborn Screening Evaluation of Krabbe Disease. ( 28592445 )
2017
10
Developmental outcomes of cord blood transplantation for Krabbe disease: A 15-year study. ( 28855403 )
2017
11
Krabbe Disease: Report of a Rare Lipid Storage and Neurodegenerative Disorder. ( 28168127 )
2017
12
Neuroradiological, neurophysiological and molecular findings in infantile Krabbe disease: two case reports. ( 27785412 )
2016
13
Adult-onset Krabbe disease presenting with an isolated form of peripheral neuropathy. ( 26840509 )
2016
14
Krabbe disease: One Hundred years from the bedside to the bench to the bedside. ( 27638583 )
2016
15
My encounters with Krabbe disease: A personal recollection of a 40-Year journey with young colleagues. ( 27638581 )
2016
16
Chaperones as potential therapeutics for Krabbe disease. ( 27638605 )
2016
17
Thickening of the cauda equina roots: a common finding in Krabbe disease. ( 27137647 )
2016
18
Synthesis and evaluation of N-alkylated analogues of aza-galacto-fagomine - potential pharmacological chaperones for Krabbe disease. ( 27545315 )
2016
19
Molecular Mechanisms of Disease Pathogenesis Differ in Krabbe Disease Variants. ( 27126738 )
2016
20
Patient fibroblasts-derived induced neurons demonstrate autonomous neuronal defects in adult-onset Krabbe disease. ( 27780934 )
2016
21
Ultrastructural Characterization of the Lower Motor System in a Mouse Model of Krabbe Disease. ( 28442746 )
2016
22
Insights into the Pathogenesis and Treatment of Krabbe Disease. ( 27491217 )
2016
23
A specific activity-based probe to monitor family GH59 galactosylceramidase - the enzyme deficient in Krabbe disease. ( 28000364 )
2016
24
Predominant Corticospinal Tract Involvement in a Late Infant with Krabbe Disease. ( 27679535 )
2016
25
Challenge of phenotype estimation for optimal treatment of Krabbe disease. ( 27638587 )
2016
26
Diffusion tensor imaging analysis of the brain in the canine model of Krabbe disease. ( 27677296 )
2016
27
New therapeutic approaches for Krabbe disease: The potential of pharmacological chaperones. ( 27638604 )
2016
28
Gene therapy for CNS diseases - Krabbe disease. ( 27525222 )
2016
29
A new mutation in an infant with Krabbe disease accompanied by enlargement of the optic nerves. ( 27040675 )
2016
30
Clinical management of Krabbe disease. ( 27638597 )
2016
31
Mutations in GALC cause late-onset Krabbe disease with predominant cerebellar ataxia. ( 26915362 )
2016
32
Adult-onset Krabbe disease presenting as acute hemiparesis and progressive demyelination detected by diffusion-weighted imaging. ( 27423612 )
2016
33
Clinical outcomes of children with abnormal newborn screening results for Krabbe disease in New York State. ( 27171547 )
2016
34
Should states adopt newborn screening for early infantile Krabbe disease? ( 26845105 )
2016
35
Ultrastructural Characterization of the Lower Motor System in a Mouse Model of Krabbe Disease. ( 27920424 )
2016
36
Metabolic profiling reveals biochemical pathways and potential biomarkers associated with the pathogenesis of Krabbe disease. ( 27638595 )
2016
37
Mesenchymal Stem Cells Yield Transient Improvements in Motor Function in an Infant Rhesus Macaque With Severe Early-Onset Krabbe Disease. ( 27559102 )
2016
38
Newborn screening for Krabbe disease in New York State: the first eight years' experience. ( 26795590 )
2016
39
RP-CARS reveals molecular spatial order anomalies in myelin of an animal model of Krabbe disease. ( 26990139 )
2016
40
Effect of vitamin D3 intake on the onset of disease in a murine model of human Krabbe disease. ( 25236689 )
2015
41
Compound Galactosylceramidase Gene (GALC) Heterozygosity in a Boy with Infantile Krabbe Disease (KD). ( 27442402 )
2015
42
Krabbe disease: involvement of connexin43 in the apoptotic effects of sphingolipid psychosine on mouse oligodendrocyte precursors. ( 26459425 )
2015
43
Clinical and molecular report of novel GALC mutations in Moroccan patient with Krabbe disease: case report. ( 26567009 )
2015
44
The Spectrum of Krabbe Disease in Greece: Biochemical and Molecular Findings. ( 26108647 )
2015
45
Regional differences in fiber tractography predict neurodevelopmental outcomes in neonates with infantile Krabbe disease. ( 25844309 )
2015
46
Midbrain morphology reflects extent of brain damage in Krabbe disease. ( 25859833 )
2015
47
Measurement of psychosine in dried blood spots - a possible improvement to newborn screening programs for Krabbe disease. ( 25762404 )
2015
48
Azasugar inhibitors as pharmacological chaperones for Krabbe disease. ( 26029356 )
2015
49
Brain angioarchitecture and intussusceptive microvascular growth in a murine model of Krabbe disease. ( 26310512 )
2015
50
Mechanism of neuromuscular dysfunction in Krabbe disease. ( 25632136 )
2015

Variations for Krabbe Disease

UniProtKB/Swiss-Prot genetic disease variations for Krabbe Disease:

71 (show all 45)
# Symbol AA change Variation ID SNP ID
1 GALC p.Gly111Asp VAR_003380 rs746487628
2 GALC p.Gly111Ser VAR_003381 rs756690487
3 GALC p.Thr112Ala VAR_003382 rs147313927
4 GALC p.Met117Leu VAR_003383
5 GALC p.Asp187Val VAR_003384 rs997021099
6 GALC p.Gly194Ala VAR_003385 rs963756824
7 GALC p.Ile250Thr VAR_003387 rs886039569
8 GALC p.Ala263Thr VAR_003388
9 GALC p.Gly284Ser VAR_003389 rs377274761
10 GALC p.Gly286Asp VAR_003390 rs199847983
11 GALC p.Asn295Thr VAR_003391 rs746922378
12 GALC p.Ser303Phe VAR_003392 rs756352952
13 GALC p.Pro318Ala VAR_003393 rs1057516642Leukodystrophy,
14 GALC p.Arg396Trp VAR_003394 rs770485731
15 GALC p.Pro400Leu VAR_003395
16 GALC p.Thr468Ser VAR_003396 rs34134328
17 GALC p.Phe514Ser VAR_003397 rs375867319
18 GALC p.Thr529Met VAR_003398 rs200960659
19 GALC p.Arg531Cys VAR_003399 rs749893889
20 GALC p.Asp544Asn VAR_003400 rs387906952
21 GALC p.Val566Gly VAR_003402
22 GALC p.Tyr567Ser VAR_003403 rs752537626
23 GALC p.Ala592Ser VAR_003404
24 GALC p.Ile599Ser VAR_003405 rs387906953
25 GALC p.Leu645Arg VAR_003407 rs780593419
26 GALC p.Gly59Arg VAR_013956
27 GALC p.Ser68Phe VAR_013957
28 GALC p.Arg79His VAR_013958 rs370117160
29 GALC p.Ile82Met VAR_013959
30 GALC p.Thr278Ile VAR_013961
31 GALC p.Tyr314Cys VAR_013963
32 GALC p.Tyr335Cys VAR_013964 rs757407613
33 GALC p.Trp426Gly VAR_013965
34 GALC p.Arg531His VAR_013966 rs200378205
35 GALC p.Gly553Arg VAR_013967 rs748573754
36 GALC p.Leu634Ser VAR_013968 rs138577661
37 GALC p.Thr668Arg VAR_013969
38 GALC p.Gly41Ser VAR_064431 rs387906955
39 GALC p.Glu130Lys VAR_064432 rs374635469
40 GALC p.Pro318Arg VAR_064433 rs387906954
41 GALC p.Gly323Arg VAR_064434
42 GALC p.Ile384Thr VAR_064435
43 GALC p.Arg396Leu VAR_064436
44 GALC p.Tyr490Asn VAR_064437 rs202135871
45 GALC p.Val681Met VAR_069512 rs200607029

ClinVar genetic disease variations for Krabbe Disease:

6 (show top 50) (show all 57)
# Gene Variation Type Significance SNP ID Assembly Location
1 GALC NM_000153.3(GALC): c.1630G> A (p.Asp544Asn) single nucleotide variant Pathogenic rs387906952 GRCh37 Chromosome 14, 88411937: 88411937
2 GALC NM_000153.3(GALC): c.1796T> G (p.Ile599Ser) single nucleotide variant Pathogenic rs387906953 GRCh37 Chromosome 14, 88407777: 88407777
3 GALC GALC, GLY553ARG single nucleotide variant Pathogenic
4 GALC GALC, IVS13DS, G-A, +1 single nucleotide variant Pathogenic
5 GALC GALC, 1-BP DEL, 1901T deletion Pathogenic
6 GALC NM_000153.3(GALC): c.857G> A (p.Gly286Asp) single nucleotide variant Pathogenic/Likely pathogenic rs199847983 GRCh37 Chromosome 14, 88434730: 88434730
7 GALC NM_000153.3(GALC): c.953C> G (p.Pro318Arg) single nucleotide variant Pathogenic rs387906954 GRCh37 Chromosome 14, 88431929: 88431929
8 GALC NM_000153.3(GALC): c.121G> A (p.Gly41Ser) single nucleotide variant Pathogenic rs387906955 GRCh37 Chromosome 14, 88459388: 88459388
9 GALC NM_000153.3(GALC): c.1161+2T> G single nucleotide variant Pathogenic rs398123175 GRCh37 Chromosome 14, 88429726: 88429726
10 GALC NM_000153.3(GALC): c.862T> C (p.Trp288Arg) single nucleotide variant Likely pathogenic rs398123177 GRCh37 Chromosome 14, 88434725: 88434725
11 GALC NM_000153.3(GALC): c.1592G> A (p.Arg531His) single nucleotide variant Pathogenic/Likely pathogenic rs200378205 GRCh37 Chromosome 14, 88411975: 88411975
12 GALC NM_000153.3(GALC): c.1700A> C (p.Tyr567Ser) single nucleotide variant Pathogenic/Likely pathogenic rs752537626 GRCh37 Chromosome 14, 88407873: 88407873
13 GALC NM_000153.3(GALC): c.1657G> A (p.Gly553Arg) single nucleotide variant Likely pathogenic rs748573754 GRCh37 Chromosome 14, 88411910: 88411910
14 GALC NM_000153.3(GALC): c.1591C> T (p.Arg531Cys) single nucleotide variant Likely pathogenic rs749893889 GRCh37 Chromosome 14, 88411976: 88411976
15 GALC NM_000153.3(GALC): c.1472delA (p.Lys491Argfs) deletion Pathogenic rs771489305 GRCh37 Chromosome 14, 88414089: 88414089
16 GALC NM_000153.3(GALC): c.955delT (p.Tyr319Metfs) deletion Pathogenic/Likely pathogenic rs786204454 GRCh37 Chromosome 14, 88431927: 88431927
17 GALC NM_000153.3(GALC): c.908+1G> A single nucleotide variant Likely pathogenic rs750524447 GRCh37 Chromosome 14, 88434678: 88434678
18 GALC NM_000153.3(GALC): c.658C> T (p.Arg220Ter) single nucleotide variant Likely pathogenic rs766310671 GRCh37 Chromosome 14, 88442796: 88442796
19 GALC NM_000153.3(GALC): c.599C> A (p.Ser200Ter) single nucleotide variant Likely pathogenic rs786204618 GRCh37 Chromosome 14, 88448571: 88448571
20 GALC NM_000153.3(GALC): c.489G> A (p.Trp163Ter) single nucleotide variant Likely pathogenic rs761550284 GRCh38 Chromosome 14, 87984487: 87984487
21 GALC NM_000153.3(GALC): c.388G> A (p.Glu130Lys) single nucleotide variant Likely pathogenic rs374635469 GRCh37 Chromosome 14, 88452887: 88452887
22 GALC NM_000153.3(GALC): c.169G> A (p.Gly57Ser) single nucleotide variant Pathogenic rs11623 GRCh37 Chromosome 14, 88459340: 88459340
23 GALC NM_000153.3(GALC): c.1543G> A (p.Glu515Lys) single nucleotide variant Likely pathogenic rs794727116 GRCh37 Chromosome 14, 88412024: 88412024
24 GALC NM_000153.3(GALC): c.205C> T (p.Arg69Ter) single nucleotide variant Pathogenic rs771111145 GRCh37 Chromosome 14, 88454858: 88454858
25 GALC NM_000153.3(GALC): c.430delA (p.Ile144Leufs) deletion Pathogenic rs775277935 GRCh37 Chromosome 14, 88452845: 88452845
26 GALC NM_000153.3(GALC): c.1153G> T (p.Glu385Ter) single nucleotide variant Pathogenic rs121908010 GRCh37 Chromosome 14, 88429736: 88429736
27 GALC GALC, 30-KB DEL, IVS10 deletion Pathogenic
28 GALC NM_000153.3(GALC): c.331G> A (p.Gly111Ser) single nucleotide variant Pathogenic rs756690487 GRCh37 Chromosome 14, 88452944: 88452944
29 GALC NM_000153.3(GALC): c.195G> C (p.Gly65=) single nucleotide variant Pathogenic/Likely pathogenic rs886042057 GRCh38 Chromosome 14, 87992970: 87992970
30 GALC NM_000153.3(GALC): c.243_244insAG (p.Ile82Argfs) insertion Pathogenic rs886043419 GRCh37 Chromosome 14, 88454819: 88454820
31 GALC NM_000153.3(GALC): c.1541T> C (p.Phe514Ser) single nucleotide variant Likely pathogenic rs375867319 GRCh37 Chromosome 14, 88412026: 88412026
32 GALC NM_000153.3(GALC): c.628A> T (p.Arg210Ter) single nucleotide variant Pathogenic rs202131052 GRCh37 Chromosome 14, 88442826: 88442826
33 GALC NM_000153.3(GALC): c.1890T> A (p.Tyr630Ter) single nucleotide variant Pathogenic/Likely pathogenic rs1057516453 GRCh38 Chromosome 14, 87939926: 87939926
34 GALC NM_000153.3(GALC): c.1851delT (p.Tyr617Terfs) deletion Likely pathogenic rs1057516433 GRCh37 Chromosome 14, 88406309: 88406309
35 GALC NM_000153.3(GALC): c.1837G> T (p.Gly613Ter) single nucleotide variant Likely pathogenic rs1057517033 GRCh37 Chromosome 14, 88406323: 88406323
36 GALC NM_000153.3(GALC): c.1670+1G> A single nucleotide variant Likely pathogenic rs749597090 GRCh38 Chromosome 14, 87945552: 87945552
37 GALC NM_000153.3(GALC): c.1586C> T (p.Thr529Met) single nucleotide variant Likely pathogenic rs200960659 GRCh38 Chromosome 14, 87945637: 87945637
38 GALC NM_000153.3(GALC): c.1426dupA (p.Ser476Lysfs) duplication Likely pathogenic rs1057517082 GRCh38 Chromosome 14, 87947791: 87947791
39 GALC NM_000153.3(GALC): c.1272_1273insTAG (p.Val425_Arg685del) insertion Likely pathogenic rs1057517372 GRCh37 Chromosome 14, 88416254: 88416255
40 GALC NM_000153.3(GALC): c.1273delG (p.Val425Tyrfs) deletion Likely pathogenic rs1057516394 GRCh37 Chromosome 14, 88416254: 88416254
41 GALC NM_000153.3(GALC): c.1065G> A (p.Trp355Ter) single nucleotide variant Likely pathogenic rs1057516270 GRCh38 Chromosome 14, 87963480: 87963480
42 GALC NM_000153.3(GALC): c.1021delG (p.Val341Serfs) deletion Likely pathogenic rs1057517382 GRCh37 Chromosome 14, 88431861: 88431861
43 GALC NM_000153.3(GALC): c.1012delG (p.Glu338Asnfs) deletion Likely pathogenic rs1057516469 GRCh38 Chromosome 14, 87965526: 87965526
44 GALC NM_000153.3(GALC): c.972delG (p.Met325Terfs) deletion Likely pathogenic rs1057516808 GRCh37 Chromosome 14, 88431910: 88431910
45 GALC NM_000153.3(GALC): c.952C> G (p.Pro318Ala) single nucleotide variant Likely pathogenic rs1057516642 GRCh38 Chromosome 14, 87965586: 87965586
46 GALC NM_000153.3(GALC): c.946C> T (p.Gln316Ter) single nucleotide variant Likely pathogenic rs776368825 GRCh38 Chromosome 14, 87965592: 87965592
47 GALC NM_000153.3(GALC): c.533G> A (p.Trp178Ter) single nucleotide variant Likely pathogenic rs968905231 GRCh37 Chromosome 14, 88450787: 88450787
48 GALC NM_000153.3(GALC): c.467_468dupGG (p.Leu157Glyfs) duplication Likely pathogenic rs1057517185 GRCh37 Chromosome 14, 88450852: 88450853
49 GALC NM_000153.3(GALC): c.442+2T> G single nucleotide variant Likely pathogenic rs1057516632 GRCh38 Chromosome 14, 87986487: 87986487
50 GALC NM_000153.3(GALC): c.415A> T (p.Lys139Ter) single nucleotide variant Likely pathogenic rs1057516673 GRCh38 Chromosome 14, 87986516: 87986516

Expression for Krabbe Disease

Search GEO for disease gene expression data for Krabbe Disease.

Pathways for Krabbe Disease

Pathways related to Krabbe Disease according to KEGG:

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

Pathways related to Krabbe Disease according to GeneCards Suite gene sharing:

(show all 17)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.71 ARSA CASP3 CHIT1 NOS2 PLA2G2A PLA2G6
2
Show member pathways
13.67 ARSA CHIT1 GALC NOS2 PLA2G2A PLA2G4A
3
Show member pathways
12.1 ARSA GALC PSAP
4
Show member pathways
12.1 CASP3 PLA2G2A PLA2G4A PLA2G6
5
Show member pathways
11.83 PLA2G2A PLA2G4A PLA2G6
6 11.67 ARSA GALC PSAP
7
Show member pathways
11.61 PLA2G2A PLA2G4A PLA2G6
8 11.27 CASP3 NOS2
9 11.26 PLA2G2A PLA2G4A
10 11.25 CASP3 NOS2 PLA2G4A
11
Show member pathways
11.24 PLA2G2A PLA2G4A
12 11.1 CASP3 PLA2G2A PLA2G4A
13 11.1 CASP3 MBP NOS2 PLA2G2A PLA2G6
14 11.05 NOS2 PLA2G4A
15 10.94 PLA2G4A PLA2G6
16 10.86 PLA2G2A PLA2G6
17 10.58 NOS2 PLA2G2A PLA2G4A

GO Terms for Krabbe Disease

Cellular components related to Krabbe Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lysosome GO:0005764 9.26 ARSA CHIT1 GALC PSAP
2 lysosomal lumen GO:0043202 8.8 ARSA GALC PSAP

Biological processes related to Krabbe Disease according to GeneCards Suite gene sharing:

(show all 15)
# Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 9.77 GALC PLA2G2A PLA2G4A PLA2G6 PSAP
2 metabolic process GO:0008152 9.72 ARSA CHIT1 GALC PLA2G4A PLA2G6
3 phosphatidic acid biosynthetic process GO:0006654 9.55 PLA2G2A PLA2G4A
4 sphingolipid metabolic process GO:0006665 9.54 GALC PSAP
5 cellular response to organic substance GO:0071310 9.52 CASP3 PSAP
6 response to bacterium GO:0009617 9.51 CHIT1 NOS2
7 arachidonic acid secretion GO:0050482 9.49 PLA2G2A PLA2G4A
8 positive regulation of blood vessel diameter GO:0097755 9.48 NOS2 PLA2G6
9 phosphatidylserine acyl-chain remodeling GO:0036150 9.46 PLA2G2A PLA2G4A
10 phosphatidylglycerol acyl-chain remodeling GO:0036148 9.43 PLA2G2A PLA2G4A
11 glycosphingolipid metabolic process GO:0006687 9.43 ARSA GALC PSAP
12 phosphatidylinositol acyl-chain remodeling GO:0036149 9.4 PLA2G2A PLA2G4A
13 phosphatidylcholine acyl-chain remodeling GO:0036151 9.33 PLA2G2A PLA2G4A PLA2G6
14 phosphatidylethanolamine acyl-chain remodeling GO:0036152 9.13 PLA2G2A PLA2G4A PLA2G6
15 lipid catabolic process GO:0016042 8.92 GALC PLA2G2A PLA2G4A PLA2G6

Molecular functions related to Krabbe Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 hydrolase activity GO:0016787 9.8 ARSA CASP3 CHIT1 GALC PLA2G2A PLA2G4A
2 calmodulin binding GO:0005516 9.54 MBP NOS2 PLA2G6
3 phospholipase A2 activity GO:0004623 9.33 PLA2G2A PLA2G4A PLA2G6
4 calcium-dependent phospholipase A2 activity GO:0047498 9.32 PLA2G2A PLA2G4A
5 phospholipase A2 activity (consuming 1,2-dipalmitoylphosphatidylcholine) GO:0102567 9.13 PLA2G2A PLA2G4A PLA2G6
6 phospholipase A2 activity consuming 1,2-dioleoylphosphatidylethanolamine) GO:0102568 8.8 PLA2G2A PLA2G4A PLA2G6

Sources for Krabbe Disease

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
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47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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