Jewish origins, there is a deficiency of both hexosaminidase A and B, moderate hepatosplenomegaly, and coarse granulations in bone marrow histiocytes. The clinical and pathologic picture is the same as in Tay-Sachs disease except for the additional signs of visceral lipid storage. Occasionally, these visceral organs are not enlarged.
In recent years, numerous variants of hexosaminidase A and B deficiency have been identified. They differ clinically from Tay-Sachs disease in having a later onset, less-extensive brain involvement (cortical neurons relatively spared and intense affection of basal ganglia, as well as cerebellar and spinal neurons). Accordingly, the clinical expression of the variants appearing in childhood, adolescence, and adult life takes the form of athetosis, dystonia, ataxia, and motor neuron paralysis; mental function can be normal. The process has also been found in a few congenital cases in which there was a rapidly progressive decline of a microcephalic infant.
Infantile Gaucher Disease (Type II Neuronopathic Form, Glucocerebrosidase Deficiency, GBA Mutation)
This is an autosomal recessive disease without ethnic predominance, first described by Gaucher in 1882. The onset of the neuronopathic form is usually before 6 months and frequently before 3 months. The clinical course is more rapid than that of Tay-Sachs disease (most patients with infantile Gaucher disease do not survive beyond 1 year and 90 percent not beyond 2 years). Oculomotor apraxia and bilateral strabismus are early signs and are accompanied by rapid loss of head control, of ability to roll over and sit, and of purposeful movements of the limbs—along with apathy, irritability, frequent crying, and difficulty in sucking and swallowing. In some cases, progression is slower, with acquisition of single words by the first year, bilateral corticospinal signs (Babinski signs and hyperactive tendon reflexes), persistent retroflexion of the neck, and strabismus. Laryngeal stridor and trismus, diminished reaction to stimuli, smallness of the head, rare seizures, normal optic fundi, enlarged spleen and slightly enlarged liver, poor nutrition, yellowish skin and scleral pigmentation, osteoporosis, vertebral collapse and kyphoscoliosis, and sometimes lymphadenopathy complete the clinical picture. The CSF is normal; the EEG is abnormal, but nonspecifically so.
The important laboratory findings are an increase in serum acid phosphatase and characteristic histiocytes (Gaucher cells) in marrow smears and liver and spleen biopsies. A deficiency of glucocerebrosidase in leukocytes and hepatocytes is diagnostic; glucocerebroside accumulates in the involved tissues. The characteristic pathologic feature is the Gaucher cell, 20 to 60 µm in diameter, with a wrinkled appearance of the cytoplasm and eccentricity of the nucleus. These cells are found in the marrow, lungs, and other viscera; neuronal storage is seldom evident. In the brain, the main abnormality is a loss of nerve cells—particularly in the bulbar nuclei, but also in the basal ganglia, cortex, and cerebellum—and a reactive gliosis that extends into the white matter.
In contrast to the type II form described above, type I