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.
Non-steroidal anti-inflammatory drugs (NSAIDs) have also been used. Hydroxychloroquine has proven effective in some cases. History
In a 1985 paper published in the Journal of the American Medical Association, McCarty and colleagues first described a case series of patients with this disorder, for which they coined the abbreviation RS3PE. RS3PE was initially thought to represent a form of seronegative rheumatoid arthritis but is now believed to be a separate syndrome. == References ==