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Galactosylceramide beta-galactosidase deficiency(KRB)

MedGen UID:
44131
Concept ID:
C0023521
Disease or Syndrome
Synonyms: Galactocerebrosidase deficiency; Globoid cell leukoencephalopathy; Krabbe Disease; Krabbe leukodystrophy; KRB; Leukodystrophy, Globoid Cell
SNOMED CT: Diffuse globoid body sclerosis (189979005); Galactosylceramide beta-galactosidase deficiency (192782005); Krabbe's leukodystrophy (192782005); Globoid cell leucodystrophy (192782005); Krabbe leucodystrophy (192782005); GCL - Globoid cell leucodystrophy (192782005); Krabbe's disease (192782005); Krabbe disease (192782005); Galactocerebroside beta-galactosidase deficiency (192782005); Diffuse globoid cell cerebral sclerosis (192782005)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): GALC (14q31.3)
 
Monarch Initiative: MONDO:0009499
OMIM®: 245200
Orphanet: ORPHA487

Disease characteristics

Excerpted from the GeneReview: Krabbe Disease
Krabbe disease comprises a spectrum ranging from infantile-onset disease (i.e., onset of extreme irritability, spasticity, and developmental delay before age 12 months) to later-onset disease (i.e., onset of manifestations after age 12 months and as late as the seventh decade). Although historically 85%-90% of symptomatic individuals with Krabbe disease diagnosed by enzyme activity alone have infantile-onset Krabbe disease and 10%-15% have later-onset Krabbe disease, the experience with newborn screening (NBS) suggests that the proportion of individuals with possible later-onset Krabbe disease is higher than previously thought. Infantile-onset Krabbe disease is characterized by normal development in the first few months followed by rapid severe neurologic deterioration; the average age of death is 24 months (range 8 months to 9 years). Later-onset Krabbe disease is much more variable in its presentation and disease course. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Characteristics  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References
Authors:
Joseph J Orsini  |  Maria L Escolar  |  Melissa P Wasserstein, et. al.   view full author information

Additional descriptions

From OMIM
Krabbe disease (KRB) 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).  http://www.omim.org/entry/245200
From MedlinePlus Genetics
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.\n\nThe most common form of Krabbe disease, called the infantile form, usually begins before the age of 1. Initial signs and symptoms typically include irritability, muscle weakness, feeding difficulties, episodes of fever without any sign of infection, stiff posture, and delayed mental and physical development. As the disease progresses, muscles continue to weaken, affecting the infant's ability to move, chew, swallow, and breathe. Affected infants also experience vision loss and seizures. Because of the severity of the condition, individuals with the infantile form of Krabbe disease rarely survive beyond the age of 2.\n\nLess commonly, Krabbe disease begins in childhood, adolescence, or adulthood (late-onset forms). Vision problems and walking difficulties are the most common initial symptoms in these forms of the disorder, however, signs and symptoms vary considerably among affected individuals. Individuals with late-onset Krabbe disease may survive many years after the condition begins.  https://medlineplus.gov/genetics/condition/krabbe-disease

Clinical features

From HPO
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Vomiting
MedGen UID:
12124
Concept ID:
C0042963
Sign or Symptom
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
Partial or complete loss of the ability to detect or understand sounds resulting from damage to the outer, middle, or inner ear structures. Causes include exposure to loud noise, ear infections, injuries to the ear, genetic, and congenital disorders.
Hydrocephalus
MedGen UID:
9335
Concept ID:
C0020255
Disease or Syndrome
Hydrocephalus is an active distension of the ventricular system of the brain resulting from inadequate passage of CSF from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation.
Neurodegeneration
MedGen UID:
17999
Concept ID:
C0027746
Cell or Molecular Dysfunction
Progressive loss of neural cells and tissue.
Seizures
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
EEG abnormality
MedGen UID:
56235
Concept ID:
C0151611
Finding
Abnormality observed by electroencephalogram (EEG), which is used to record of the brain's spontaneous electrical activity from multiple electrodes placed on the scalp.
CNS demyelination
MedGen UID:
137898
Concept ID:
C0338474
Disease or Syndrome
A loss of myelin from nerve fibers in the central nervous system.
Diffuse cerebral atrophy
MedGen UID:
108958
Concept ID:
C0598275
Finding
Diffuse unlocalised atrophy affecting the cerebrum.
Peripheral demyelination
MedGen UID:
451074
Concept ID:
C0878575
Pathologic Function
A loss of myelin from the internode regions along myelinated nerve fibers of the peripheral nervous system.
Sensorimotor neuropathy
MedGen UID:
207266
Concept ID:
C1112256
Disease or Syndrome
Increased CSF protein
MedGen UID:
329971
Concept ID:
C1806780
Finding
Developmental regression
MedGen UID:
324613
Concept ID:
C1836830
Disease or Syndrome
Loss of developmental skills, as manifested by loss of developmental milestones.
Hyperactive deep tendon reflexes
MedGen UID:
335355
Concept ID:
C1846176
Finding
Decreased nerve conduction velocity
MedGen UID:
347509
Concept ID:
C1857640
Finding
A reduction in the speed at which electrical signals propagate along the axon of a neuron.
Progressive spasticity
MedGen UID:
347171
Concept ID:
C1859520
Finding
Spasticity that increases in degree with time.
Motor deterioration
MedGen UID:
356495
Concept ID:
C1866284
Finding
Loss of previously present motor (i.e., movement) abilities.
Autoimmune thrombocytopenia
MedGen UID:
116621
Concept ID:
C0242584
Disease or Syndrome
The presence of thrombocytopenia in combination with detection of antiplatelet antibodies.
Decerebrate rigidity
MedGen UID:
41430
Concept ID:
C0011103
Pathologic Function
A condition characterized by abnormal posturing of the limbs that is associated with injury to the brainstem. This may occur as a clinical manifestation or induced experimentally in animals. The extensor reflexes are exaggerated leading to rigid extension of the limbs accompanied by hyperreflexia and opisthotonus. This condition is usually caused by lesions which occur in the region of the brainstem that lies between the red nuclei and the vestibular nuclei. In contrast, decorticate rigidity is characterized by flexion of the elbows and wrists with extension of the legs and feet. The causative lesion for this condition is located above the red nuclei and usually consists of diffuse cerebral damage. (From Adams et al., Principles of Neurology, 6th ed, p358)
Hypertonia
MedGen UID:
10132
Concept ID:
C0026826
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
Muscular hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
A condition of decreased tone of the skeletal muscles and diminished resistance to passive stretching.
Progressive spasticity
MedGen UID:
347171
Concept ID:
C1859520
Finding
Spasticity that increases in degree with time.
Autoimmune thrombocytopenia
MedGen UID:
116621
Concept ID:
C0242584
Disease or Syndrome
The presence of thrombocytopenia in combination with detection of antiplatelet antibodies.
Recurrent fever
MedGen UID:
811468
Concept ID:
C3714772
Sign or Symptom
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
A disorder characterized by loss of optic nerve fibers. It may be inherited or acquired. Acquired causes include ischemia, optic nerve neuropathy, glaucoma, trauma, radiation, brain tumors, and multiple sclerosis. It leads to vision disturbances.
Blindness
MedGen UID:
99138
Concept ID:
C0456909
Disease or Syndrome
Blindness is the condition of lacking visual perception defined as visual perception below 3/60 and/or a visual field of no greater than 10 degrees in radius around central fixation.
Abnormal flash visual evoked potentials
MedGen UID:
870329
Concept ID:
C4024772
Finding
Anomaly of the visual evoked potentials elicited by a flash stimulus, generally a flash of light subtending an angle of at least 20 degrees of the visual field and presented in a dimly lit room.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVGalactosylceramide beta-galactosidase deficiency
Follow this link to review classifications for Galactosylceramide beta-galactosidase deficiency in Orphanet.

Recent clinical studies

Diagnosis

McKelvie P, Vine P, Hopkins I, Poulos A
Pathology 1990 Oct;22(4):235-8. doi: 10.3109/00313029009086670. PMID: 2091007

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