Krabbe disease

Krabbe disease (also known as globoid cell leukodystrophy or galactosylceramide lipidosis) is a rare, often fatal degenerative disorder that affects the myelin sheath of the nervous system. This condition is inherited in an autosomal recessive pattern. The disease is named for the Danish neurologist Knud Haraldsen Krabbe.

Incidence
Krabbe disease occurs in about 1 in 100,000 births. A higher incidence, about 1 in 6,000, has been reported in some Arab communities in Israel. Scandinavian countries have comparatively high rates of the disease, reported to be 1 in 50,000 births. Krabbe disease may also be found in cats and in dogs, particularly Westies and Cairn Terriers.

Causes
Krabbe disease is caused by mutations in the GALC gene located on chromosome 14 (14q31), which causes a deficiency of an enzyme called galactocerebrosidase. 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.

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, 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.

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.