A Correlative Synopsis of the Leukodystrophies

Abstract

Leukodystrophies are disorders affecting primarily oligodendroglial cells or myelin. Another necessary criteria for defining a leukodystrophy is that the disorder has to be of endogenous origin with a pattern compatible with genetic transfer of a metabolic defect. The clinical criterion of a steadily progressive deterioration of function must also be included. Much of the material presented during the conference related to three leukodystrophies from which subclasses with a relatively uniform clinical presentation can be distinguished and about which a considerable body of consistent biochemical information is available. These disorders are metachromatic leukodystrophy (MLD), globoid leukodystrophy (GLD, also referred to as Krabbe's disease) and adrenoleukodystrophy (ALD). Discussion was focused to the pathophysiology of the more prevalent "classical" subclass of each of these disorders; discussion of clinical variants was in the context of what we could learn about the more prevalent form. Finally, because of time restraints, most of the discussion on the final day was centered around MLD. This clinical disorder was used as a starting point for discussion of questions both specific to MLD as well as those questions common to all leukodystrophies. The discussion of GLD and ALD was more restricted and only points relevant to those specific leukodystrophies were discussed. Information from the presentation not dealing directly with these human disorders is also summarized.

The authors of this article were charged with preparing an "end of conference" summary, and with guiding a discussion to better define our understanding, or lack thereof, of the present state of knowledge concerning leukodystrophies. In order to structure the discussion we reviewed the information presented concerning the sequence of steps involved in the pathophysiology of the leukodystrophies. We then invited discussion concerning what was, or was not, known about each of the steps involved. In the interest of a coherent presentation, we have only occasionally attributed discussion comments to individual participants any names appearing in this synopsis refere to authors of articles contributing to the topic of leukodystrophies. Any new insight into understanding of the leukodystrophies which were developed results from the collective wisdom of the participants. The converse does not follow, since this report was not circulated among the participants, the authors of this article take solely responsibility for any misinterpretation or oversimplification of what was said.

Key words

Leukodystrophies, man, animals - Metachromatic leukodystrophy - Myelin globoid leukodystrophy - Sphingolipids - Psychosine - Adrenoleukodystrophy, long chain fatty acids - Genetic defects