The Human Biochemical Genetics Section studies selected biochemical defects and other genetic disorders to provide insight into cellular mechanisms and to care for neglected groups of rare disease patients. Members of the section use the NIH Clinical Center to evaluate individuals with cystinosis, a lysosomal membrane defect leading to storage of the amino acid cystine and causing kidney failure in childhood. Section physicians document the beneficial effects of cystine-depleting therapy with oral cysteamine, and respond to scores of inquiries every year from cystinosis patients and their physicians throughout the world. Another focus of the section involves Hermansky-Pudlak syndrome (HPS), a rare disorder of oculocutaneous albinism and bleeding due to abnormal formation of intracellular vesicles; some patients also suffer a fatal pulmonary fibrosis. Members of the section have discovered three of the nine genetic subtypes of HPS, and serve as authorities on the clinical and basic research aspects of this group of diseases.
A third major focus involves ciliopathies, in which cilia (hair-like protrusions from cells) are defective. Special emphasis is placed on autosomal recessive polycystic kidney disease and congenital hepatic fibrosis (ARPKD/CHF), Alstrom syndrome, and the discovery of new genetic causes of ciliopathies. Members of the section are collaborating with investigators from the National Center for Advancing Translational Sciences (NCATS) to treat a late-onset muscle disease called GNE myopathy using sialic acid, whose production is defective in that disorder. The treatment consists of providing N-acetylmannosamine, which forms sialic acid in the body. Other rare disorders studied by the section include Chediak-Higashi disease, Erdheim-Chester disease, albinism, vascular calcification disorders, mitochondrial diseases and congenital disorders of glycosylation. Finally, members of the section lead the NIH Undiagnosed Diseases Program (UDP), which evaluates undiagnosed patients, attempts to diagnose very rare disorders and discovers new diseases using state-of-the-art genetic techniques.
Dr. William A. Gahl earned his B.S. in biology from the Massachusetts Institute of Technology in 1972 and his M.D. from the University of Wisconsin in 1976. He obtained a Ph.D. degree in oncology research from Wisconsin's McArdle Laboratories for Cancer Research in 1981 and served as pediatric resident and chief resident at the University of Wisconsin hospitals from 1976-80. In 1984, he completed clinical genetics and clinical biochemical genetics fellowships at the NIH's Interinstitute Medical Genetics Training Program, which he directed from 1989 to 1994. Dr. Gahl's research has focused on the natural history of rare metabolic disorders and the discovery of new genetic diseases. He elucidated the basic defects in cystinosis and Salla disease, i.e., deficiencies of the lysosomal membrane transporters that carry cystine and sialic acid, respectively, out of the lysosome.
Dr. Gahl also demonstrated effective therapy for nephropathic cystinosis, bringing cysteamine to new drug approval by the Food and Drug Administration. His group described the natural history of Lowe syndrome, alkaptonuria, autosomal recessive polycystic kidney disease, Chediak-Higashi disease, GNE myopathy, and Hermansky-Pudlak syndrome (HPS), a disorder of oculocutaneous albinism, bleeding, and pulmonary fibrosis. His lab discovered the genetic bases of gray platelet syndrome, Hartnup disease, arterial calcification due to deficiency of CD73, 3-methylglutaconic aciduria type III, 3 types of HPS, and neutropenia due to VPS45 deficiency. He has published more than 350 peer-reviewed papers and trained 36 biochemical geneticists. He established American Board of Medical Specialties certification for medical biochemical genetics. He served one the board of directors of the ABMG, as president of the Society for Inherited Metabolic Disorders, and was elected to the American Society for Clinical Investigation and the Association of American Physicians.
Dr. Gahl received the Dr. Nathan Davis Award for Outstanding Government Service from the AMA, the Service to America Medal in Science and the Environment, and numerous other awards.
Last Updated: December 7, 2015