Krabbe disease

Krabbe disease

Incidence
Worldwide, Krabbe disease occurs in about 1 in 100,000–200,000 births. A higher incidence (6 cases per 1,000 live births) has been reported in a few isolated communities in Israel.

Causes
Krabbe disease is caused by mutations in the GALC gene, which causes a deficiency of an enzyme called galactosylceramidase. The buildup of undigested fats affects the growth of the nerve’s protective myelin sheath (the covering that insulates many nerves) and causes severe degeneration of mental and motor skills. As part of a group of disorders known as leukodystrophies, Krabbe disease results from the imperfect growth and development of myelin. myelin  (mī'ə-lĭn)  Pronunciation Key A whitish, fatty substance that forms a sheath around many vertebrate nerve fibers. Myelin insulates the nerves and permits the rapid transmission of nerve impulses. The white matter of the brain is composed of nerve fibers covered in myelin.

Presentation
Infants with Krabbe disease are normal at birth. Symptoms begin between the ages of 3 and 6 months with irritability, inexplicable crying, fevers, limb stiffness, seizures, feeding difficulties, vomiting, and slowing of mental and motor development. Other symptoms include muscle weakness, spasticity, deafness, optic atrophy and 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, nerve demyelination and degeneration, and destruction of brain cells.

Treatment
Although there is no cure for Krabbe disease, bone marrow transplantation has been shown to benefit mild 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.

Prognosis
In infants, the disease is generally fatal before age 2. Patients with a later onset form of the disease have a milder course of the disease and live significantly longer.

Advocacy
Former Buffalo Bills quarterback Jim Kelly has been a leader in gaining recognition and research funding for the disease, following the diagnosis of his son, Hunter, with Krabbe disease in 1997. Hunter Kelly died of the disease August 5, 2005 at the age of 8. He was the longest known living survivor of infantile Krabbe disease.

Wikipedia links

 * The Myelin Project
 * The Stennis Foundation