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 (1885–1961). Signs and symptoms
Symptoms in asymptomatic infantile-onset (<12 months after birth) and later-onset Krabbe disease present themselves differently. Of individuals with infantile-onset Krabbe disease, 85–90% display progressive neurologic deterioration in infancy and death before the age of two. Symptoms include irritability, fevers, limb stiffness, seizures, feeding difficulties (like GERD), vomiting, staring episodes, 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.10–15% of individuals with later-onset Krabbe disease have a much slower disease progression. These individuals may also display symptoms such as esotropia, slurred speech, and slow development or loss of motor milestones. Causes
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.
The incidence rate is extremely low in Japan, with between 5 and 10 cases per 1,000,000 live births. In the United States, Krabbe disease occurs in approximately 1 out of every 100,000 live births. Scandinavian countries report incidence rates of one in 50,000 births. In certain communities Krabbe disease is much more frequent, such as the Druze community in Israel, which has an incidence rate of 6 out of every 1,000 live births. This higher rate is thought to be due in part to a high frequency of consanguineous marriages. Almost 35% of all Druze marriages were found to be between first-cousin familial relations. There have been no reported cases of Krabbe disease among the Jewish community.Time of onset also varies in frequency by location. Early infantile Krabbe Disease is the most common form of the disease overall, but Nordic communities tend to have even higher rates of early infantile onset Krabbe disease, while Southern European countries have higher incidences of late-onset cases. It is difficult to estimate the incidence of adult-onset Krabbe disease, due to discrepancies in classifying cases late-onset versus adult-onset. Society and culture
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 eight.