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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 sphingolipidosis and is inherited in an autosomal recessive pattern. The disease is named after Danish neurologist Knud Krabbe (1885–1961).
About 10–15% of individuals with later-onset KD 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.
The buildup of unmetabolized adversely affects the growth of the nerve's protective myelin sheath (the covering that insulates many ) resulting in demyelination and severe progressive degeneration of motor skills. As part of a group of disorders known as leukodystrophy, KD results from the imperfect growth and development of myelin.
Galactosylceramidase deficiency also results in a buildup of the glycosphingolipid psychosine, which is toxic to , a type of non-neuronal cells 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.
New York, Missouri, and Kentucky(KRS 214.155) include KD in their newborn screening panel. Indiana started screening in 2020.
A 15-year study on the developmental outcomes of children with KD who underwent HSCT in the first seven weeks after birth found that patients have a better prognosis for both lifespan and functionality, with a slower disease progression. Even symptomatic individuals with later-onset Krabbe disease may benefit from HSCT if diagnosed early enough. Umbilical-cord blood is typically used as the source for the transplant stem cells. Clinical trials for gene therapy are currently enrolling patients.
Feeding tube are used to circumvent feeding difficulties and prevent aspiration. A simultaneous gastrostomy tube insertion and Nissen fundoplication procedure is commonly performed to prevent the need for a secondary surgical procedure. Individuals with KD with severe motor deficits tend to be more susceptible to overfeeding, as they require less calorie consumption, thus consuming fewer calories than caretakers may expect. Also, some evidence indicates that routine vaccines may accelerate disease progression; many individuals with KD tend to not follow traditional vaccination procedures.
Krabbe disease occurs in about one in 100,000 births. Because the disease is genetic, incidence rates vary widely from population to population. The incidence rate is extremely low in Japan, with between 5 and 10 cases per 1,000,000 live births. In the United States, KD occurs in about one of every 100,000 live births. Scandinavian countries report incidence rates of one in 50,000 births. Books.Google.com In certain communities, KD is much more frequent, such as the Druze community in Israel, which has an incidence rate of six of every 1,000 live births, 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. No cases of KD have been reported among the Jewish community.
The time of onset also varies in frequency by location. Early infantile KD is the most common form of the disease overall, but Nordic communities tend to have even higher rates of early-infantile onset KD, while Southern European countries have higher incidences of late-onset cases. Estimating the incidence of adult-onset KD is difficult due to discrepancies in classifying cases as late-onset versus adult-onset.
In 2016, Cove Ellis, a child from Georgia, United States, was diagnosed with the disease. Her family and local community has worked to raise awareness of the disease and helped pass "Cove's Law".
This article incorporates public domain text from the United States National Library of Medicine and the National Institute of Neurological Disorders and Stroke.
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