The clinical study of neurogenetic diseases provides the context in which the goals of improved diagnosis and potential treatment modalities are identified. Several new phenotypes have been recognized including a number of cases of deficiency of hexosaminidase A presenting as motor neuron disease; glycerol kinase deficiency presenting as acidemia and stupor without mental retardation; and biopterin deficiency presenting as familial dystonia. A number of rare phenotypes have also been identified including Tay-Sachs disease in a young non-Jewish child, 2 cases of juvenile Krabbe's disease, an unusual presentation of multiple sulfatase deficiency, an unusual case of San Filippo A disease, a mild variant of Morquio's syndrome, a case of arylsulfatase activator deficiency, a case of Menke's disease in a female infant, and several cases of acute neuronopathic Gaucher's disease. A large number of typical neurogenetic diseases have been confirmed by studies performed in this protocol. Studies of chorionic villus samples (CVS) have allowed the prenatal diagnosis of a number of lysosomal storage diseases. We have developed an accurate method for biochemically distinguishing phenotypes pre-symptomatically. Finally, a clinical trial of enzyme replacement is being conducted in Gaucher's disease. The application of gene transfer to human disease is under consideration.
