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Krabbe disease (KD) (also known as globoid cell leukodystrophy or galactosylceramide lipidosis) is a rare and often fatal lysosomal storage disease that results in progressive damage to the nervous system. KD involves dysfunctional metabolism of sphingolipids and is inherited in an autosomal recessive pattern. The disease is named after the Danish neurologist Knud Krabbe (1885–1965).
|A histopathology slide of a brain with Krabbe disease showing giant cells with PAS stain inclusions ("globoid cells") within astrocytic gliosis and loss of myelinated fibers.|
|Usual onset||Within 3 to 6 months of birth, but can present in childhood or even adulthood|
|Types||Infantile, juvenile and adult|
|Causes||Mutation of GALC gene|
|Risk factors||Parents who are heterozygous (only one copy) for the mutation to the GALC gene.|
|Diagnostic method||Histopathology, genetic testing|
|Prevention||Prenatal diagnosis and screening of at-risk couples and subsequent termination of pregnancy|
|Treatment||Symptomatic and supportive treatment only, but stem cell transplantation may be beneficial|
|Prognosis||One, two, and three year survival rates of 60%, 26%, and 14%, respectively|
Signs and symptomsEdit
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. Juvenile and adult-onset cases of Krabbe disease also occur, which have similar symptoms but slower progression.
Krabbe disease is caused by mutations in the GALC gene located on chromosome 14 (14q31), which is inherited in an autosomal recessive manner. Mutations in the GALC gene cause a deficiency of an enzyme called galactosylceramidase. In rare cases, it may be caused by a lack of active saposin A (a derivative of prosaposin).
The buildup of unmetabolized lipids adversely affects the growth of the nerve's protective myelin sheath (the covering that insulates many nerves) resulting in demyelination and severe progressive 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, which is toxic to oligodendrocytes, a type of non-neuronal cell found in the nervous system, collectively termed neuroglia.
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.
Although there is no known 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. Cord blood transplants from unrelated donors have been successful in stopping the disease as long as they are given before overt symptoms appear.
In infantile Krabbe disease, death usually occurs in early childhood. A 2011 study found one, two, and three year survival rates of 60%, 26%, and 14%, respectively. A few survived for longer. Patients with late-onset Krabbe disease tend to have a slower progression of the disease and live significantly longer.
Krabbe disease occurs in about one in 100,000 births. A higher incidence, about six in 1,000, has been reported in certain communities in Israel. Scandinavian countries report incidence rates of one in 50,000 births.
Society and cultureEdit
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.
Cove Ellis is a child from Georgia, United States, that was diagnosed with the disease in early 2016. Cove's family, along with her community, have worked to raise awareness of the disease and helped pass Cove's Law. This law allows parents the option to have prenatal screening for the disease which can potentially save the child.
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This article incorporates public domain text from the United States National Library of Medicine and the National Institute of Neurological Disorders and Stroke.