Krabbe disease

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 Krabbe (1885–1965).^[2]

Illinois, Kentucky,^[3] and Pennsylvania have laws to test for Krabbe and other diseases at birth. There is a movement in Maine and other states to adopt such regulations.

Signs and 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,^[4] blindness, paralysis, and difficulty when swallowing. Prolonged weight loss may also occur. Juvenile- and adult-onset cases of Krabbe disease also occur, which have similar symptoms but slower progression.

Causes

Krabbe disease is caused by mutations in the GALC gene located on chromosome 14 (14q31),^[5] which causes a deficiency of an enzyme called galactosylceramidase.^[6] 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. Psychosine has been suggested to cause axonal degeneration in both the central and peripheral nervous systems by disrupting lipid rafts and may play a role in Krabbe disease.^[7][8]

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.

Treatment

Although no cure for Krabbe disease is known, 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. Cord blood transplants have been successful in stopping the disease as long as they are given before overt symptoms appear.^[9]

Prognosis

In infants, the disease is generally fatal before age two. Patients with late-onset Krabbe disease tend to have a slower progression of the disease and live significantly longer.

Epidemiology

Krabbe disease occurs in about one in 100,000 births.^[10] A higher incidence, about six in 1,000,^[10] has been reported in certain communities in Israel.^[11] Scandinavian countries have comparatively high rates of the disease, reported to be one in 50,000 births.^[12] Krabbe disease may also be found in cats^[13] and in dogs, particularly Westies and Cairn Terriers.^[14][15] The disease may also be found in dolphins.

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.

See also

• The Myelin Project
• The Stennis Foundation
• Maria Luisa Escolar

References

This article incorporates public domain text from the United States National Library of Medicine and the National Institute of Neurological Disorders and Stroke.

External links

• Dr. Maria Escolar Speaks about Krabbe Disease - Infantile Krabbe Disease Parent Education Program
• GeneReviews/NCBI/NIH/UW entry on Krabbe disease
• OMIM entries on Krabbe disease
• The Stennis Foundation
• 00174 at CHORUS

• The Hunter's Hope Foundation
• DTI as a Tool to Identify Infants with Krabbe Disease in Need of Urgent Treatment - Study to aid detection and treatment of Krabbe Disease