OTC is an X-linked disorder of nitrogen homeostasis which has phenotypic variability in males and females. Variability in males is principally a function of mutational variability whereas variability in females is principally a function of random X-chromosome reactivation. The goal of this project is to investigate the phenotypic variability in adult women who have a mutation at the ornithine transcarbamylase (OTC) locus. Recent evidence suggests that many of these women have detectable metabolic abnormalities and may be at risk for life-threatening hyperammonemia. At-risk adult females for this study will be ascertained through 270 pedigrees of OTC deficient probands already identified by the Johns Hopkins Center for Urea Cycle Disorders; additional at-risk females will be recruited as new OTC deficient patients are referred. In pedigrees ascertained through a proband with OTC deficiency, untested at-risk adult females will be asked to take an allopurinol test to determine their carrier status. This test requires the careful collection of four timed urine specimens during a 24 hour period. Urine and plasma samples will also be obtained to measure biochemical variables associated with OTC deficiency. Self-administered questionnaires covering family history, demographic, education, dietary and medical information will be distributed to these women. Based on the results of the allopurinol tests, carrier and non-carrier females will be identified and compared to determine if carriers experience excess morbidity or premature mortality, decreased educational achievement or voluntary restriction of dietary protein. In addition, the relationship between abnormal biochemical measurements and unfavorable clinical outcomes in carriers will be examined. Identification of specific abnormalities in adult carrier females will allow better and more appropriate treatment for carriers of this mutant allele.
| Maestri, N E; Lord, C; Glynn, M et al. (1998) The phenotype of ostensibly healthy women who are carriers for ornithine transcarbamylase deficiency. Medicine (Baltimore) 77:389-97 |
| Carducci, M A; Choti, M; Maestri, N E et al. (1998) Allopurinol-induced pyrimidinuria in cancer patients. In Vivo 12:271-4 |
| Maestri, N E; Brusilow, S W; Clissold, D B et al. (1996) Long-term treatment of girls with ornithine transcarbamylase deficiency. N Engl J Med 335:855-9 |
