In the past few years, there has been an increase in research involving the connection between urea cycle disorders and other major diseases, such as cancer, AIDS and sickle cell anemia. Researchers have found at least two major areas of interest in relation to urea cycle disorders. The first connection involves changes in urea cycle enzyme production in cancer patients with bone marrow transplants undergoing chemotherapy. Because the production of urea cycle enzymes takes place in the liver, drugs toxic to the liver, such as those used in chemotherapy, are observed to be damaging urea cycle enzyme production. Therefore, these bone marrow transplant patients are developing the same accumulation of ammonia (hyperammonemia) seen in children with urea cycle disorders. Another study has found changes (polymorphisms) in these enzymes in the general population. This raises questions as to the significance of these variations on the overall health of the individual.

Another connection to major diseases relates to the drugs that were developed through the Orphan Drug Act for treating the children with of urea cycle disorders. These drugs, pioneered by children with urea cycle disorders, are now being used in Phase II clinical trials for other disorders, and at major cancer research institutions across the nation. The drugs appear to halt the production of cancer cells in numerous cancers, including melanoma and lymphoma.

Large research institutions are now looking at urea cycle disorders, a previously limited disease, as a new key to developing treatments in other areas of medicine. This new interest will bring more resources to bear for urea cycle research, and our ultimate goal of a cure for the children and adults suffering from these devastating disorders. (For more information, click here to go to the UCDC Contact Registry.)

Advancements in technologies such as tandem mass spectrometry (MS/MS) have made it possible to screen all newborns for argininosuccinate synthetase deficiency (citrullinemia), argininosuccinate lyase (ASA), and arginase deficiency (AG). NUCDF participated in grassroots movement to require every state to screen newborns at birth, and many states have now added these urea cycle disorders to their mandated screening programs. Research into screens for OTC and CPS deficiencies has been initiated.

Comprehensive newborn screening helps prevent brain damage and other severe consequences of delayed diagnoses and saves children’s lives. We have seen the difference that comprehensive newborn screening has made in the positive outcomes of newborns with citrullinemia, ASA and arginase deficiency and will continue to support research into screens for OTC and CPS.