There are now more than 40 lysosomal storage diseases in which the biochemical abnormalities have been determined. The main ones are listed in Table 36-3, which was adapted originally from the review of Kolodny and Cable. Each has an identified genetic cause. In addition to the sphingolipidoses, which are the lysosomal storage diseases most likely to be encountered in the first year of life, the table includes the storage diseases that may not appear clinically until a later age (in childhood and adolescence)—to be considered later in this chapter. The frequency of each of the various types, as detected in a comprehensive study of the Australian population, is given by Meikle and colleagues and generally accords with the ordering below. A broad perspective on the frequency of the lysosomal disorders can be appreciated from the report of the Australian national referral laboratory. There were 545 cases (75 detected prenatally) over a 16-year period, a calculated frequency of 1 case per 7,700 live births. This is close to the estimate in the United States, which is approximately 1 per 5,000 births.
The more frequent types of lysosomal storage diseases are as follows: 1. Tay-Sachs disease (GM2 gangliosidosis) and variants such as Sandhoff disease 2. Infantile Gaucher disease 3. Infantile Niemann-Pick disease 4. Infantile GM1 generalized gangliosidosis 5. Krabbe globoid-body leukodystrophy 6. Farber lipogranulomatosis 7. Pelizaeus-Merzbacher and other sudanophilic leukodystrophies 8. Spongy degeneration (Canavan-van Bogaert-Bertrand disease) 9. Alexander disease 10. Zellweger encephalopathy 11. Lowe oculorenal-cerebral disease
In the following descriptions, we have summarized the clinical and pathologic features of each of the diseases listed above and have italicized the characteristic clinical signs and corroborative laboratory tests. Leigh disease, which may appear in this age group, is described with the mitochondrial diseases, further on in this chapter.
Tay-Sachs Disease (GM2 Gangliosidosis, Hexosaminidase A Deficiency, HEXA Mutation)