Amaurotic family idiocy

Infantile Amaurotic Familial Idiocy (Tay-Sachs Disease) Gaucher s Disease Niemann-Pick Disease Leukodystrophies and Fabry s Disease... 

Infantile Amaurotic Familial Idiocy (Tay-Sachs Disease)... 

Infantile amaurotic familial idiocy is a hereditary disease transmitted as an autosomal recessive trait resulting in the accumulation of gangliosides in the brain cells. The main clinical manifestations are dementia, paralysis, and blindness. The disease has been most frequently described among Jews, and it is generally restricted to children 6 months to 3 years old. However, late infantile and even juvenile forms have been described. 

The lipoid compounds that accumulate in the ganglion cells are gangliosides. In infantile amaurotic familial idiocy, the grey matter contains 10-20 times the amount of gangliosides found in normal individuals. In contrast, the levels of cerebrosides and sphingomyelins are normal. (A case has been described in which the levels of both cerebrosides and gangliosides of the brain were increased.)... 

The term gangliosides was introduced by Kjlenk for neuraminic acid-containing glycolipids which he found (1939—1942) in the brains of subjects with infantile amaurotic family idiocy. The neuraminic acid content of gangliosides permitted differentiation from other carbohydrate-containing lipids such as cere-brosides which accumulate in Gaucher s disease. 

With the exception of TSD, lipid data are scarce in the literature for the various forms of amaurotic family idiocies, and the subclassification as outlined is mainly based on clinical and histochemical differences. Since tinctorial properties of a chemical compound are much more dependent on the physico-chemical state than on the concentration (Hagberg et al. 1965), histochemistry is limited to qualitative studies and does not allow a quantitation of lipid storage. 

There is no question that there is ganglioside storage in TSD. In addition, recent analyses have shown that gangliosides are also increased in the late-infantile amaurotic family idiocy. Variable findings have been reported for the juvenile form, and increased gangliosides have not yet been found in the adult variety. 

The diagnosis of CAFI should be considered when the symptomatology of amaurotic family idiocy develops immediately at birth or during the first weeks thereafter. Biopsies from brain and rectum permit recognition of the histologic abnormalities of amaurotic family idiocy. 

It is now well established that great majority of cases of TSD occur in Jewish families. Exceptions were reported by Falkenheim (1901), Starck (1920), Catel (1943), Aronson et al. (1960). Probably, the incidence of TSD in races other than the Jewish would actually be even smaller than reported wdth more complete knowledge of the type of amaurotic family idiocy in some subjects and of the ancestry in others. 90% of 219 Tay-Sachs children of Aronson and Volk (1962) belonged to the Jewish race as jugded by their religion. TSD in Japanese families was reported by Cordes and Horner (1929) and Murakami (1957). From epidemiologic studies on the frequency of a deficiency of fructose-1-phosphate aldolase (Volk et al. 1964), the incidence of TSD in Jews is 100 times that of non-Jews. This is discussed in more detail in the chapter by Fuhrmann. 

There are no significant abnormalities of the main serum lipid classes in TSD. An increased NANA content (Saifer and Gerstenfield 1962) is found in a variety of diseases, but an elevated globulin neuraminic acid to globulin protein ratio was found to be a good statistical indicator for biochemical distinction of amaurotic family idiocy from other disease groups. 

Fig. 1. Infantile amaurotic family idiocy. HE-stain. Enlargement 230-fold. Ballooned motor ganglion cell of the brain stem. (Reproduced by courtesy of Prof. P. B. Diezel)...

Histologic and histochemical properties of material from brain biopsy or rectum biopsy render further evidence for the diagnosis, and secure to some degree the differentiation of TSD from other types of amaurotic family idiocy. Lipid analyses from brain tissue with the demonstration of the increase in Tay-Sachs ganglioside finally provide conclusive evidence for the diagnosis. 

There are many signs and symptoms common to LIAFI as well as TSD, such as hyperacusis, muscular twitching, irritability and decreasing response to the environment. However, bouts of screaming or laughter are rare and, in contrast to TSD, initial symptoms include loss of intellectual capacity and impairment of speech rather than progressive motor weakness and impaired mobility. In general, the symptoms resemble more those of the juvenile type of amaurotic family idiocy. 

IV. Juvenile Amaurotic Family Idiocy Definition and Introduction... 

In contrast to the infantile type of amaurotic family idiocy (Tay-Sachs disease), none of the patients with JAFI came from Jewish families (Jervis 1959, Diezel 1962). JAFI in a Negro girl could be confirmed at autopsy. Familial occurrence was observed in the majority of reported cases. Details on the heredity of JAFI are given by Fuhrmann in a separate chapter. 

In contrast, therefore, to Tay-Sachs disease, to some cases of late-infantile amaurotic family idiocy and to one case of congenital amaurotic family idiocy, there is no evidence of storage of a specific ganglioside in JAFI. The solution to yet unanswered questions may come from analyses of particularly involved areas instead of unselected parts, since, in contrast to Tay-Sachs disease, the biochemical lesion responsible for the development of JAFI, does not result in ganglioside storage which is as impressive as that observed in Tay-Sachs disease. 

The literature contains a number of cases reported as Tay-Sachs disease, late-infantile amaurotic family idiocy, congenital amaurotic family idiocy and gargoylism with foam cells in various visceral organs. While storage of gangliosides was demonstrated for a fraction of these cases the ganglioside was identified in only a few. 

Since the homogeneity of this particular class of amaurotic family idiocy is not yet established, a brief review of reported cases seems justified (see table 6). 

In the publication by Jatzkewitz and Sandhoff (1963) (see page 236) of a possible case of late-infantile amaurotic family idiocy with storage of GgntI there was also evidence of lipid storage in spleen, thymus and liver. 

A. Saifer, A. Kanof, and B. W. Volk Progression of amaurotic family idiocy as reflected by serum and cerebrospinal fluid changes. Amer. J. Med. 24, 390 (1958). 

M. P. Valsamis, and B. W. Volk Infantile amaurotic family idiocy. Occurrence, genetic considerations, and pathophysiology in the non-Jewish infant. Pediatrics 26, 229 (I960). 

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