OBJECTIVES: I. Determine the phenotypic heterogeneity of patients with genetic disorders
including their clinical spectrum and natural history.
II. Develop and evaluate novel methods for the treatment of genetic disorders including
metabolic manipulation, enzyme manipulation, enzyme replacement, enzyme transplantation, and
gene transfer techniques in these patients.
III. Develop and evaluate methods for the prenatal diagnosis of genetic disorders using
improved cytogenetic, biochemical, and nucleic acid techniques and amniotic fluid cells or
chorionic villi in these patients.
Patients are evaluated annually or biannually, depending on disease status and progression.
Patients undergo a complete medical history, an extensive family pedigree, and a physical
examination. Patients undergo general laboratory, imaging, physiologic, and clinical
laboratory studies according to their disease type. Patients undergo specialized laboratory
studies including plasma and leukocyte enzyme assays, quantitative urinary
mucopolysaccharides and oligosaccharides, urine and plasma glycolipids, plasma and urine
amino acids, urine organic acids, lymphoblastoid culture, DNA isolation from peripheral
leukocytes, skin biopsy for fibroblast culture (if indicated), and medical photography.
Patients also receive consultations with various specialties including ophthalmology, ENT,
cardiology, pulmonary, gastroenterology/nutrition, hematology, neurology, orthopedics,
rehabilitation medicine/physical therapy, and dermatology.
- Suspected diagnosis (homozygous or heterozygous) of a genetic disorder including, but
not limited to, one of the following: Tay-Sachs disease (adult form) Congenital
erythropoietic porphyria Galactosemia Mitochondrial myopathy Globoid cell
leukodystrophy (Krabbe disease) Methylmalonic acidemia Isovaleric acidemia Morquio
type A Glycogen storage disease type 1AB Ornithine aminotransferase deficiency Ceroid
lipofuscinosis Glutaric aciduria type 1 Citrullinemia Other malformation syndromes,
lysosomal storage disorders, or peroxisomal disorders