Krabbe disease
From Wikipedia, the free encyclopedia
Krabbe disease (also known as
globoid cell leukodystrophy[1] or
galactosylceramide lipidosis) is a rare, often fatal degenerative disorder that affects the
myelin sheath of the
nervous system. It is a form of
sphingolipidosis, as it involves dysfunctional metabolism of
sphingolipids. This condition is inherited in an
autosomal recessive pattern. The disease is named after the Danish
neurologist Knud Haraldsen Krabbe (1885-1965).
[2]
Incidence
Krabbe disease occurs in about 1 in 100,000 births.
[3] A higher incidence, about 1 in 6,000,
[3] has been reported in some
Arab communities in
Israel.
[4] Scandinavian countries have comparatively high rates of the disease, reported to be 1 in 50,000 births.
[5] Krabbe disease may also be found in cats
[6] and in dogs, particularly
Westies and
Cairn Terriers.
[7][8]
Causes
Krabbe disease is caused by
mutations in the
GALC gene located on
chromosome 14 (14q31),
[9] which causes a deficiency of an
enzyme called
galactocerebrosidase. In rare cases it may be caused by a lack of active
saposin A.
The build-up of unmetabolized lipids affects the growth of the
nerve's protective myelin sheath (the covering that insulates many
nerves) and causes severe degeneration of motor skills. As part of a group of disorders known as
leukodystrophies, Krabbe disease results from the imperfect growth and development of myelin.
GALC deficiency also results in a build-up of a
glycosphingolipid called
Psychosine. It has been suggested Psychosine causes axonal degeneration in both the CNS and PNS by disrupting
lipid rafts and may play a role in Krabbe disease.
[10][11]
Symptoms
Infants with Krabbe disease are normal at birth. Symptoms begin between the ages of 3 and 6 months with irritability,
fevers, limb stiffness,
seizures, feeding difficulties,
vomiting,
and slowing of mental and motor development. In the first stages of the
disease, doctors often mistake the symptoms for those of
cerebral palsy. Other symptoms include muscle weakness, spasticity, deafness, optic atrophy, optic nerve enlargement,
[12]
blindness, paralysis, and difficulty when swallowing. Prolonged weight
loss may also occur. There are also juvenile- and adult-onset cases of
Krabbe disease, which have similar symptoms but slower progression.
Diagnosis
The disease may be diagnosed by its characteristic grouping of certain cells (
multinucleated globoid cells), nerve demyelination and degeneration, and destruction of brain cells. Special stains for
myelin (e.g.;
luxol fast blue) may be used to aid diagnosis.
Prognosis
In infants, the disease is generally fatal before age 2. Patients
with late-onset Krabbe disease tend to have a slower progression of the
disease and live significantly longer.
Treatment
Although there is no cure for Krabbe disease,
bone marrow transplantation
has been shown to benefit cases early in the course of the disease.
Generally, treatment for the disorder is symptomatic and supportive.
Physical therapy may help maintain or increase
muscle tone and circulation. A recent study in the
New England Journal of Medicine reports that
cord blood transplants have been successful in stopping the disease as long as they are given before overt symptoms appear.
[13]
Advocacy
Former
Buffalo Bills quarterback
Jim Kelly
has been a leader in gaining recognition and research funding for
Krabbe disease, following the diagnosis of his son, Hunter, in 1997.
Hunter Kelly died of the disease on August 5, 2005, at the age of 8.
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