Tay-Sachs Disease with Visceral Involvement and its Relation to Gargoylism

There is an accumulation of clinical, neuropathological, and chemical evidence pointing to the clear separation of Tay-Sachs disease from other forms of amaurotic family idiocy. One point of distinction is the rarity of visceral lipidosis in the infantile form of the disease. We have, in fact, only been able to find reference to five cases of Tay-Sachs disease in which the neuronal lipidosis was associated with signs of a more generalized storage disease, and in some of these the evidence is not very convincing. Davison and Jacobson (1936) reported foam cells in the spleen, and vacuoles containing sudanophil lipid in the cells of the liver and renal tubules. Brouwer (1936) also found foam cells in the spleen of his case. Marburg (1942) described vacuoles in the liver which were filled with lipid staining in the same way as that in the nerx c cells. This case was unusual because of the severe atrophy and fibrosis of some of the other glandular organs. It is difficult to assess the significance of these changes as part of a primary lipidosis, and it is certainly unlikely that the lipid in the organs of these three cases was chemically identical to that stored in the neurones. The brain in Tay-Sachs disease stores large amounts of ganglioside, and an essential component of this substance is neuraminic acid. Neuraminic acid is not normally present in the spleen, liver, or kidneys, so that an accumulation of ganglioside would not be expected to occur in these sites as the result of deranged local metabolism. On the other hand, it is well known that in certain lipidoses there may be differences between the substances or mixtures of substances that are stored in the brain and in the viscera. In gargoylism the nerve cells contain an increased amount of ganglioside (though usually much less so than in Tay-Sachs disease), while the other affected organs predominantly store polysaccharides. The latter material is readily diffusable, so that the involved tissues, after ordinary fixation, are characterized histologically by the presence of empty vacuoles. There are two recorded examples of undoubted Tay-Sachs disease, in which a similar change has been found in some of the visceral organs. Turban (1944) described a non-Jewish child who died at the age of 2 years after a progressive neurological illness. The characteristic cherry-red spot at the macula had been noted. Analysis of the cerebral cortex by Klenk showed a fivefold increase in ganglioside, and histologically the brain was typical of Tay-Sachs disease. Empty vacuoles were a conspicuous feature of the cells of the liver and renal tubules, and foam cells, also devoid of lipid, were present in the pulmonary alveoli and their walls. More extensive visceral involvement of the same type was described by Norman, Urich, Tingey, and Goodbody (1959) in their case of infantile amaurotic idiocy. This child had shown typical macular changes and also came from a non-Jewish family. There was hepatomegaly and slight enlargement of the spleen. Empty vacuoles were present in the parenchyma of the liver, kidney, pancreas, and thyroid. Empty foam cells were numerous in the liver, spleen, lymph nodes, thymus, intestines, bone-marrow, and lungs, both in the alveoli and their septa. The case to be reported in this paper is a further example of this unusual combination of neural and visceral lesions in a chemically verified case of Tay-Sachs disease. Additional interest is given by the detailed clinical examination which was made at a time when hypotonia was the main neurological abnormality. Case Report Clinical Finding This child (J.C.) was first referred under the care of Professor D. V. Hubble in December 1960, for investigation of motor and mental retardation, first suspected three months previously, at the age of 9 months. She was the first child of normal parents, with a