Search

Urea cycle disorders (UCDs) are rare inherited metabolic conditions that impair the effectiveness of the urea cycle responsible for removing excess ammonia from the body. The estimated incidence of UCDs is 1:35 000 births, or approximately 113 new patients with UCD per year. This review summarizes neuropsychological outcomes among patients with the eight UCDs in reports published since 1980. Rates of intellectual disabilities published before (and including) 2000 and after 2000 were pooled and compared for each UCD. Since diagnoses for UCDs tended to occur earlier and better treatments became more readily available after the turn of the century, this assessment will characterize the extent that current management strategies have improved neuropsychological outcomes. The pooled sample included data on cognitive abilities of 1649 individuals reported in 58 citations. A total of 556 patients (34%) functioned in the range of intellectual disabilities. The decline in the proportion of intellectual disabilities in six disorders, ranged from 7% to 41%. Results from various studies differed and the cohorts varied with respect to age at symptom onset, age at diagnosis and treatment initiation, current age, severity of the metabolic deficiency, management strategies, and ethnic origins. The proportion of cases with intellectual disabilities ranged from 9% to 65% after 2000 in the seven UCDs associated with cognitive deficits. Positive outcomes from some studies suggest that it is possible to prevent or reverse the adverse impact of UCDs on neuropsychological functioning. It is time to "raise the bar" in terms of expectations for treatment effectiveness. [ABSTRACT FROM AUTHOR]

Abstract: Blood phenylalanine (Phe) levels provide a practical and reliable method for the diagnosis and monitoring of metabolic status in patients with phenylketonuria (PKU). To assess the reliability of blood Phe levels as a predictive biomarker of clinical outcomes in the development of treatments for PKU, a systematic literature review and meta-analysis of published trials of PKU, which included Phe level and neurological and dietary compliance outcome measures, was conducted. Within-study correlations between Phe level and intelligence quotient (IQ) were extracted from 40 studies. Significant, proportional correlations were found during critical periods (from 0 to 12 years of age) for early-treated patients with PKU (r =−0.35; 95% confidence interval [CI]: −0.44 to −0.27), where each 100μmol/l increase in Phe predicted a 1.3- to 3.1-point reduction in IQ. Similar significant correlations were observed between IQ and mean lifetime Phe level for early-treated patients (r =0.34; 95% CI: −0.42 to −0.25), where each 100μmol/l increase in Phe predicted a 1.9- to 4.1-point reduction in IQ. Moderate correlations were found between concurrent Phe level and IQ for early-treated patients. In conclusion, these results confirm a significant correlation between blood Phe level and IQ in patients with PKU, and support the use of Phe as a predictive biomarker for IQ in clinical trials. [Copyright &y& Elsevier]

Context: Untreated maternal phenylketonuria (PKU) increases risk for developmental problems in offspring. The extent to which this risk is reduced by maternal dietary therapy at various stages of pregnancy is not known.Objective: To determine whether dietary treatment during pregnancy of women with PKU affects developmental outcomes of offspring.Design: The Maternal PKU Collaborative Study, an ongoing, longitudinal prospective study begun in 1984.Setting: A total of 78 metabolic clinics and obstetrical offices in the United States, Canada, and Germany.Participants: A total of 253 children of women with PKU (n = 149), with untreated mild hyperphenylalaninemia (n = 33), or without known metabolic problems (comparison group; n = 71) were followed up to age 4 years.Intervention: Women with PKU were offered a low-phenylalanine diet prior to or during pregnancy with the aim of maintaining metabolic control (plasma phenylalanine < or =10 mg/dL [< or =605 micromol/L]). Women with mild hyperphenylalaninemia, who had plasma phenylalanine levels of no more than 10 mg/dL (605 micromol/L) on a normal diet, were not treated.Main Outcome Measures: Children's scores on cognitive and behavioral assessments (McCarthy Scales of Children's Abilities, Test of Language Development, Achenbach Child Behavior Checklist, Vineland Adaptive Behavior Scales, and Home Observation for Measurement of the Environment), compared by maternal metabolic status at 0 to 10 weeks', 10 to 20 weeks', and after 20 weeks' gestation.Results: Scores on the McCarthy General Cognitive Index decreased as weeks to metabolic control increased (r = -0.58; P<.001). Offspring of women who had metabolic control prior to pregnancy had a mean (SD) score of 99 (13). Forty-seven percent of offspring whose mothers did not have metabolic control by 20 weeks' gestation had a General Cognitive Index score 2 SDs below the norm. Overall, 30% of children born to mothers with PKU had social and behavioral problems.Conclusions: Our data suggest that delayed development in offspring of women with PKU is associated with lack of maternal metabolic control prior to or early in pregnancy. Treatment at any time during pregnancy may reduce the severity of delay. [ABSTRACT FROM AUTHOR]

Objectives. This study identified factors predicting adherence to medical recommendations in maternal phenylketonuria, which can result in severe fetal damage. Methods. Sixty-nine women with phenylketonuria, 68 of their acquaintances, and 69 women with diabetes mellitus were interviewed annually for 5 years, A model in which each stage in the maternal phenylketonuria life cycle represented a treatment-related goal provided a means to assess adherence. Results. At the stages of prevention of unplanned pregnancy, treatment initiation, and diet continuation throughout pregnancy, attitudes and social support were associated with adherence to medical recommendations. No specific variables were associated with outcome at reproductive decision making, but women with phenylketonuria were more likely to delay making a decision, resulting in unplanned and, hence, untreated or late-treated pregnancy. Conclusions. Women with phenylketonuria differed from their acquaintances and diabetic women in many respects, suggesting that special programs are needed. Greater emphasis on reproductive decision making is especially needed. Interventions that focus on improving social support networks and attitudes about treatment may increase adherence to recommendations [ABSTRACT FROM AUTHOR]

Objectives. The purpose of this study was to measure the effectiveness of resource mothers in reducing adverse consequences of maternal phenylketonuria. Methods. Nineteen pregnancies in the resource mothers group were compared with 64 pregnancies in phenylketonuric women without resource mothers. Weeks to metabolic control and offspring outcome were measured. Results. Mean number of weeks to metabolic control was 8.5 (SE = 2.2) in the resource mothers group, as compared with 16.1 (SE=1.7) in the comparison group. Infants of women in the resource mothers group had larger birth head circumferences and higher developmental quotients. Conclusions. The source mothers program described here improves metabolic control in pregnant women with phenylketonuria. [ABSTRACT FROM AUTHOR]