The Phenotype of Ostensibly Healthy Women Who Are Carriers for Ornithine Transcarbamylase Deficiency

Abstract

The combination of desmopressin (DDAVP) and behavioral therapy for treatment of nocturnal enuresis was compared with use of each of these modes alone. We randomly assigned 226 enuretic children being treated in primary care clinics of a major medical center in the largest health maintenance organization in Israel into 3 groups: Group A) DDAVP plus behavioral therapy (double-blind); Group B) behavioral therapy plus placebo (double-blind); and Group C) DDAVP alone (open group). DDAVP (20 micrograms/naris) and placebo were administered by intranasal spray. Both pharmacologic and behavioral therapy were initiated after a 2-week observation period and continued for 8 weeks. All patients were followed for 2 months after completion of treatment. A significant reduction in the number of wet nights/week was registered for all 3 groups: 49% in Group A, 45% in Group B, and 19% in Group C. After controlling for confounding factors, no significant difference in effect was noted among the 3 types of treatment during the trial period. However, on follow-up the results for the DDAVP patients were significantly less stable compared with the other 2 groups (p = 0.015). Minor side effects were registered, but none of the participants withdrew from the trial. To our knowledge, this is the largest randomized trial of nocturnal enuresis conducted to date. Our findings suggest that simply discussing the problem with the patient and family leads to improvement, and that behavioral therapy is also beneficial. DDAVP can help, but the relapse rate on discontinuation is high.

Ornithine Transcarbamylase Deficiency with Persistent Abnormality in Cerebral Glutamate Metabolism in Adults

“…[2][3][4][5][6][7][8][9][10][11][12][13] C]-␤-glucose and its primary metabolites (glutamate C5, glutamine C5, glutamate C1 plus glutamine C1, aspartate C1, and bicarbonate) were all readily observed in this frontal brain examination (Fig 4), confirming that the technique is applicable to the frontal brain regions studied.…”

“…Either [1-13 C]-glucose (n ϭ 3 for OTCD patients, n ϭ 2 for control subjects) or [2][3][4][5][6][7][8][9][10][11][12][13] C]-glucose (n ϭ 3 for OTCD patients, n ϭ 2 for control subjects) infusion was performed by one author (O.A.). An infusion of 99% 13 C-enriched glucose, at 0.23 g per kilogram of body weight (20% wt/vol), was administered intravenously as a single dose during 15 minutes.…”

“…The time courses of glutamate C4 and C2 and [1][2][3][4][5][6][7][8][9][10][11][12][13] C]-glucose appearing in the brain of one control subject (Fig 3c) and of one OTCD patient (Fig 3d) illustrate the principal differences between OTCD patients and control subjects.…”

“…The remainder may manifest behavioral aberrations and learning disabilities, protein intolerance, cyclical vomiting, strokelike episodes, and HA coma (11)(12)(13)(14). Specific neurocognitive deficits exist in these patients (15).…”

Clinical, biochemical, and molecular spectrum of hyperargininemia due to arginase I deficiency

“…Deficiencies of all of the enzymes of the urea cycle have been identified, and although each specific disorder results in accumulation of different metabolites, they (except for hyperargininemia) usually present in the newborn period or in early infancy with hyperammonemic encephalopathy and hyperglutaminemia [Batshaw et al, 1980;Maestri et al, 1999;Msall et al, 1984]. Most of these disorders (N-acetyl glutamate synthase deficiency, carbamoyl phosphate synthetase I deficiency, argininosuccinate synthetase deficiency, argininosuccinate lyase deficiency, and arginase I deficiency or hyperargininemia) are inherited in an autosomal recessive fashion, whereas ornithine transcarbamylase deficiency is X-linked [Maestri et al, 1998]. The overall prevalence of these conditions is estimated to be of 1:8200 in the United States [Brusilow and Maestri, 1996].…”