Krabbe
disease
Alternative names
Globoid cell leukodystrophy;
Galactosylcerebrosidase deficiency; Galactosylcereamidase
deficiency
Definition
Krabbe disease is an inherited
disorder characterized by a deficiency of the
enzyme galactocerebroside beta-galactosidase (i.e.,
galactosylcereamidase) and resulting in destruction
of myelin (a fatty material that surrounds and
insulates many of the nerves).
Causes
and risks
Krabbe disease is inherited as an autosomal
recessive trait. It has a higher incidence among
people of Scandinavian descent, but it generally
affects about 1 in 150,000 infants. Absence
of the enzyme galactocerebroside beta-galactosidase
causes increasing destruction of myelin. The
end result is a progressive destruction of the
nervous system.
Krabbe disease, like many other storage diseases,
has an early onset form and a late onset form.
In the early form, symptoms begin in the first
months of life with feeding problems and failure
to thrive, unexplained fevers, and vomiting.
Changes in muscle tone are frequent, and seizures
may begin very early, and are severe. Visual
and hearing losses are progressive. Affected
children eventually assume a rigid unusual body
position called decerebrate posturing. Death
follows shortly thereafter, usually before the
second year of life.
The late onset form of the disease begins in
late childhood or early adolescence. Visual
problems progressing to blindness may be the
first symptom. Gait disturbance (ataxia) and
muscle rigidity lead to progressive disability.
Prevention
Genetic counseling is recommended
for prospective parents with a family history
of Krabbe disease. Carrier states may be recognized
by decreased galactocerebroside beta-galactosidase
levels in their white blood cells or skin fibroblasts.
Prenatal diagnosis is possible by measuring galactocerebroside
beta-galactosidase levels in cultured amniotic
fluid cells or from cultured chorionic villi cells.
Symptoms
- Family history of Krabbe disease, especially
in a sibling
- Infantile irritability and sensitivity to
loud sounds
- Feeding difficulties
- Vomiting
- Failure to thrive
- Unexplained fevers
- Changing muscle tone from floppy to rigid
- Seizures, deterioration in function
of nerves in brain and body
- Infant who ceases to follow faces or motion
(symptomatic of blindness)
- Decreased hearing that progresses to deafness
Signs
and tests
Examination of the retina
may show optic atrophy. Abnormal posturing may
be evident (opisthotonos and decerebrate posturing)
in late stages of the disorder. There may be signs
of deafness.
Tests:
- Galactocerebroside beta-galactosidase levels
(levels can be measured from the serum, white
blood cells, chorionic villi, and fibroblasts)
- CSF total protein may be increased
- MRI of the head is the best test to
reveal abnormal white matter of the brain
- CT of the head
- Nerve conduction velocity showing delayed
nerve conduction and evidence of demyelination
- Presence of abnormal Globoid cells in biopsy
tissue of the nervous system
- Genetic testing may be available for the
glycosylceramidase gene (GALC)
Treatment
There is no specific treatment for Krabbe disease.
Bone marrow transplantation (with its own risks)
has been attempted in early stages of the disease.
It is too early to know if the new bone marrow
can fully restore the brain to health in the
small number of patients who have had this treatment.
In the future there may be 'enzyme replacement
therapy', but it is in the early stages of development
as of late 2001. Prevention, for example
by prenatal or genetic testing, is available.
Support
groups
United Leukodystrophy Foundation
Prognosis
The outcome is likely to
be poor. For example, infantile-onset cases die
before 2 years of age on average. Later onset
cases have survived into adulthood with neurologic
disease.
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