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 nerves 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.Galactosylceramidase deficiency also results in a buildup of a glycosphingolipid called psychosine, which is toxic to oligodendrocytes, a type of non-neuronal cell found in the nervous system, collectively termed neuroglia. Diagnosis
There are a few ways to help pinpoint the presence of Krabbe disease. Newborn screening for Krabbe disease includes assaying dried blood cells for GALC enzyme activity and molecular analysis for evidence of GALC enzyme mutations. Infants displaying low enzyme activity and/or enzyme mutations should be referred for additional diagnostic testing and neurological examination. 0-5% GALC enzyme activity is observed in all symptomatic individuals with Krabbe disease. High concentration of psychosine in dried blood spots may also be identified as a marker for Krabbe disease. A 2011 study discovered that individuals with Krabbe disease, more so in later-onset individuals, tend to have an abnormal increase in CSF protein concentration.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 include Krabbe in the newborn screening panel.
Individuals with Krabbe disease with severe motor deficits tend to be more susceptible to overfeeding, as they require less calorie consumption and thus consume fewer calories than what caretakers may expect. There is also evidence that routine vaccines may accelerate disease progression; many individuals with Krabbe disease tend to not follow traditional vaccination procedures. Prognosis
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, with a few surviving longer. Patients with late-onset Krabbe disease tend to have a slower progression of the disease and live significantly longer. Epidemiology
This disease does not only impact humans, but other animals such as monkeys, mice, and dogs have been observed to develop Krabbe disease as well. While certain gene deletions are more frequent than others, novel mutations resulting in Krabbe disease have been discovered worldwide. Most commonly, the underlying cause of the disease is a deletion of a GALC gene, which causes a deficiency in the GALC enzyme. This is the circumstance in 80% of patients who have European and Mexican origins. The mortality rate of early infantile Krabbe disease is 90% before the age of two. Later onset of symptoms is associated with longer life expectancy, with older children generally surviving two to seven years after the initial diagnosis.Krabbe disease occurs in about one in 100,000 births. Because the disease is genetic, incidence rates vary widely from population to population.