Dr. Gahl studies rare inborn errors of metabolism through the observation and treatment of patients in the clinic and through biochemical, molecular biological, and cell biological investigations in the laboratory. His group focuses on a number of diseases, including cystinosis, Hermansky-Pudlak syndrome, alkaptonuria, and disorders of sialic acid metabolism.
Dr. Gahl has a long-standing research interest in cystinosis, a lysosomal storage disorder caused by a mutation in the CTNS gene that occurs in one in every 100,000 to 200,000 live births. The CTNS gene encodes the protein cystinosin, and mutations in CTNS lead to impaired transport of cystine out of lysosomes and the formation of cystine crystals in most cells in the body. Untreated, the disease causes kidney failure in childhood, along with a host of other severe complications. Over the past three decades, Dr. Gahl's laboratory has elucidated the pathogenesis of this disease and demonstrated the safety and efficacy of cysteamine therapy, a treatment that depletes cells of cystine. In fact, cysteamine therapy, along with kidney transplantation, has improved the future for many cystinosis patients from a life filled with debilitating complications to one marked by chronic yet manageable symptoms. Dr. Gahl's group is following about 125 pre- and post-transplant cystinosis patients to track their clinical course, identify additional mutations, and document complications of the disease and therapy.
Another of Dr. Gahl's major research areas is Hermansky-Pudlak syndrome (HPS), a group of vesicle formation and transport disorders characterized by albinism and bleeding. In some cases, HPS is also characterized by pulmonary fibrosis or colitis. HPS was first described in 1959 and was thought to be a single-gene disorder affecting vesicles involved in intracellular transport. Since then, nine human genes - including three discovered by Dr. Gahl's group - have been identified as causes of HPS. Because some HPS patients have no identifiable genetic mutation, it is believed that proper vesicle formation and movement may require other genes. No treatment has been developed for the underlying disorder, but Dr. Gahl's group has continues to pursue the identification of an anti-fibrotic agents through basic and clinical research. Another topic of investigation is alkaptonuria, a condition in which mutations in the HGD gene cause a buildup of homogentisic acid (HGA), which discolors the eyes and damages the connective tissues in major joints and cardiac valves. Dr. Gahl's group conducted continues to investigate the use of nitisinone, an inhibitor of HGA production, for the treatment of alkaptonuria.
Dr. Gahl also studies disorders of sialic acid, a charged sugar. Deficiency of sialic acid production causes a severe muscle-wasting disease that often forces patients into wheelchairs, ultimately leading to death by respiratory failure. Excess sialic acid is also detrimental to health, resulting in three rare childhood diseases characterized by growth retardation and developmental delays. One of these diseases is so rare that only seven patients have been identified worldwide. Dr. Gahl's laboratory has done mutation analysis on six of them. Research on treating sialic acid deficiency is progressing steadily.
Dr. Gahl's group includes national experts in autosomal recessive polycystic kidney disease and congenital hepatic fibrosis, Chediak-Higashi syndrome, Gray Platelet syndrome, and albinism.
Dr. Gahl also directs the NIH Undiagnosed Diseases Program (UDP), an initiative that attempts to obtain a diagnosis for patients who have long been unable to achieve that goal. The UDP intends to identify new diseases that will provide insights into normal cell biology, biochemistry and physiology. This Program is expanding to a nationwide network of centers.
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Last Updated: August 26, 2013