Chemical Pathology of Krabbe Disease: The Occurrence of Psychosine and Other Neutral Sphingoglycolipids

Abstract

In 1916, the Danish neurologist, Knud Krabbe (9), delineated a new type of infantile familial diffuse brain sclerosis and gave the first description of the characteristic giant cells, which are the histological hallmark of the disease. During the 60s, cumulative analytical and experimental findings resulted in the concept of Krabbe disease as galactosylceramidosis, a concept corroborated by the demonstration of a generalized deficiency of galactosylceramide β-galactosidase (21). But further investigations disclosed also additional enzymic deficiencies, involving the degradation of galactosylsphingosine (13), monogalactosyl diglyceride (37) and lactosylceramide (38), all substrates with a terminal β-galactosidic linkage. Though this does not imply the assumption of a multiple enzyme deficiency, since a single enzyme seems to catalyze the hydrolysis of galactosylceramide and of the three other substrates (12, 14, 32, 37), it does open up new approaches in our search for a better comprehension of the pathophysiology of Krabbe disease. The impaired degradation of galactosylceramide appears to be directly involved in the formation of the globoid cells (1, 15, 20), but it cannot by itself explain other characteristics of the disease, such as the lack of demonstrable accumulation of galactosylceramide in extra-neural organs or in brain outside the globoid cells.