The clinical study of neurogenetic diseases provides the context in which the goals of improved diagnosis and potential treatment modalities are identified. Several new clinical phenotypes have been recognized including a number of cases of hexosaminidase, a deficiency presenting as motor neuron disease, glycerol kinase deficiency presenting as acidemia and stupor without mental retardation, biopterin deficiency presenting as familial dystonia and a severe variant of cholesterol ester storage disease presenting with advanced liver disease. A number of rare phenotypes have also been identified including Tay-Sachs Disease in a young non-Jewish child, two 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 Monquio's Syndrome, a case of arylsulfatase activation deficiency, a case of Menke's Disease in a female infant and an unusal variant of mitochondrial encephalomyelopathy. A large number of typical neurogenetic diseases have been confirmed by studies performed in this protocol. Studies of chorionic villus samples have allowed early prenatal diagnosis of certain lysosomal storage disorders. Clinical trials of enzyme replacement in Gaucher's disease, biopterin supplementation in diurnally variant dystonia and cholesterol restriction therapy in C and D variants of Niemann- Pick Disease are being conducted. The application of gene transfer to human disease is under consideration.
