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Galactosylceramide beta-galactosidase deficiency(GCL; GLD)

MedGen UID:
44131
Concept ID:
C0023521
Disease or Syndrome
Synonyms: Galactocerebrosidase deficiency; Globoid cell leukoencephalopathy; Krabbe Disease; Krabbe leukodystrophy; Leukodystrophy, Globoid Cell
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, Orphanet
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 homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
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)
 
Gene (location): GALC (14q31.3)
OMIM®: 245200
Orphanet: ORPHA487

Definition

Krabbe disease is characterized by infantile-onset progressive neurologic deterioration and death before age two years (85%-90% of individuals) or by onset between age one year and the fifth decade with slower disease progression (10%-15%). Children with the infantile form appear to be normal for the first few months of life but show extreme irritability, spasticity, and developmental delay before age six months; psychomotor regression progresses to a decerebrate state with no voluntary movement. The onset and progression in the late-onset forms can be quite variable. Individuals can be clinically normal until weakness, vision loss, and intellectual regression become evident. The onset of symptoms and clinical course can be variable even among siblings. [from GTR]

Additional descriptions

From GeneReviews
Krabbe disease is characterized by infantile-onset progressive neurologic deterioration and death before age two years (85%-90% of individuals) or by onset between age one year and the fifth decade with slower disease progression (10%-15%). Children with the infantile form appear to be normal for the first few months of life but show extreme irritability, spasticity, and developmental delay before age six months; psychomotor regression progresses to a decerebrate state with no voluntary movement. The onset and progression in the late-onset forms can be quite variable. Individuals can be clinically normal until weakness, vision loss, and intellectual regression become evident. The onset of symptoms and clinical course can be variable even among siblings.  https://www.ncbi.nlm.nih.gov/books/NBK1238
From OMIM
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).  http://www.omim.org/entry/245200
From GHR
Krabbe disease (also called globoid cell leukodystrophy) is a degenerative disorder that affects the nervous system. It is caused by the shortage (deficiency) of an enzyme called galactosylceramidase. This enzyme deficiency impairs the growth and maintenance of myelin, the protective covering around certain nerve cells that ensures the rapid transmission of nerve impulses. Krabbe disease is part of a group of disorders known as leukodystrophies, which result from the loss of myelin (demyelination). This disorder is also characterized by the abnormal presence of globoid cells, which are globe-shaped cells that usually have more than one nucleus.The symptoms of Krabbe disease usually begin before the age of 1 year (the infantile form). Initial signs and symptoms typically include irritability, muscle weakness, feeding difficulties, episodes of fever without any sign of infection, stiff posture, and slowed 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.Less commonly, onset of Krabbe disease can occur in childhood, adolescence, or adulthood (late-onset forms). Visual problems and walking difficulties are the most common initial symptoms in this form of the disorder, however, signs and symptoms vary considerably among affected individuals.  https://ghr.nlm.nih.gov/condition/krabbe-disease

Clinical features

Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Involuntary movements of the eye that are divided into two types, jerk and pendular. Jerk nystagmus has a slow phase in one direction followed by a corrective fast phase in the opposite direction, and is usually caused by central or peripheral vestibular dysfunction. Pendular nystagmus features oscillations that are of equal velocity in both directions and this condition is often associated with visual loss early in life. (Adams et al., Principles of Neurology, 6th ed, p272)
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
Finding
Blindness is the condition of lacking visual perception due to physiological or neurological factors.
Abnormal flash visual evoked potentials
MedGen UID:
870329
Concept ID:
C4024772
Anatomical Abnormality
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.
Failure to thrive
MedGen UID:
115900
Concept ID:
C0231246
Finding
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:
5453
Concept ID:
C0018772
Finding
A condition in which a person partially loses the ability to hear sounds in one or both ears.
Seizure Disorders
MedGen UID:
4506
Concept ID:
C0014544
Disease or Syndrome
A brain disorder characterized by episodes of abnormally increased neuronal discharge resulting in transient episodes of sensory or motor neurological dysfunction, or psychic dysfunction. These episodes may or may not be associated with loss of consciousness or convulsions.
Hydrocephalus
MedGen UID:
9335
Concept ID:
C0020255
Disease or Syndrome
Autosomal recessive nonsyndromic hydrocephalus is characterized by onset in utero of enlarged ventricles due to a disturbance of cerebrospinal fluid accumulation. Affected individuals may have neurologic impairment (summary by Drielsma et al., 2012). Hydrocephalus can also be caused by Arnold-Chiari malformation, atresia of foramen of Magendie, stenosis of aqueduct of Sylvius (307000), toxoplasmosis, hydranencephaly, etc. Furthermore, it develops in infancy or childhood in achondroplasia (100800) and in Hurler disease (607014). Genetic Heterogeneity of Congenital Hydrocephalus See also autosomal recessive HYC2 (615219), caused by mutation in the MPDZ gene (603785) on chromosome 9p. An X-linked form (307000) is caused by mutation in the L1CAM gene on (308840) on chromosome Xq28.
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.
Neurodegeneration
MedGen UID:
17999
Concept ID:
C0027746
Cell or Molecular Dysfunction
Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.
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
Increased concentration of protein in the cerebrospinal fluid.
Hyperactive deep tendon reflexes
MedGen UID:
335355
Concept ID:
C1846176
Finding
Psychomotor regression, progressive
MedGen UID:
340556
Concept ID:
C1850493
Finding
Loss of developmental skills, as manifested by loss of developmental milestones.
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:
75778
Concept ID:
C0272286
Disease or Syndrome
The presence of thrombocytopenia in combination with detection of antiplatelet antibodies.
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:
75778
Concept ID:
C0272286
Disease or Syndrome
The presence of thrombocytopenia in combination with detection of antiplatelet antibodies.
Episodic fever
MedGen UID:
82922
Concept ID:
C0277799
Finding
Cycles of fever with intervening periods of normothermia.

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. PMID: 2091007

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