Studies in Globoid (Krabbe) Leukodystrophy

Infantile Globoid Cell Leucodystrophy – (Krabbe's Disease) A clinical and genetic study of 32 Swedish cases 1953–1967

“…The markedly decreased content of sul~hatides was first reported by SVENNERHOLM in 1961SVENNERHOLM in (published 1963. A metabolic block between cerebrosides and cerebroside sulfates has been postulated by AUSTIN (1963). As a support for this hypothesis, BACHHAWAT et al (1967) claimed to have demonstrated decreased activities in GLD of the enzyme cerebroside-~ul~hotransferase from white and grey matter and kidney tissue.…”

“…Contrary to the Wallerian degeneration, in which the myelin lipids, including cerebrosides, are removed, the nerves from subjects with G L D revealed the accumulation of a PAS positive lipid, most probably cerebroside, in Schwann cells and endoneurial phagocytes. I t is well known that the globoid cells and bodies in the brain in G L D accumulate cerebrosides (AUSTIN 1963). N o globoid cells and bodies have been seen in the peripheral nerves in GLD.…”

Some Lipid Diseases of the Brain

“…There have indeed been other terms used (for details see Poser 1965) and these include the pre-lipoid type of Scholz, the brown metachromatic type of von Hirsch and Peiffer and sulphatide lipidosis introduced by Austin. Our own biochemical studies have always indicated, as did those of Edgar (1957), that there was an increased content of hexosamine in the brain, as well as an increased sulphatide in this series, as found by Austin (1960). It would seem that the use either of the term metachromatic leucodystrophy or possibly of sulphatide lipidosis is permissible but the former has been chosen for this presentation.…”

“…The biochemical estimations can be difficult to interpret for there is a loss of myelin lipids with the presence of cholesterol esters in only some cases (see Fig 9). Austin (1963) has suggested that the ratio cerebroside to sulphatide is raised as compared with the normal ratio and this is true in a few of my 8 cases. Austin has separated the actual globoid bodies and finds that sulphatide is reduced in them whereas cerebroside is present in a relatively large amount.…”

“…Note the increase in sulphatide and reduction of cerebroside disease and my experience has been that in all the 31 cases examined there has been a raised total hexosamine level, and this fact formed the original basis for diagnosis. Austin (1958, 1960) and Jatzkewitz (1958, 1960) obtained raised sulphatide figures in their cases, and of the 20 cases studied by me since 1960 all have shown a sulphatide content raised above the normal for the age. These two features can therefore be regarded as diagnostic.…”