Comparison of Methods of Initial Ascertainment in 58 Cases of Propionic Acidemia Enrolled in the Inborn Errors of Metabolism Information System Reveals Significant Differences in Time to Evaluation and Symptoms at Presentation.

OBJECTIVES: To compare time to evaluation and symptoms at diagnosis of propionic acidemia (PA) by method of ascertainment, and to explore correlations between genotype and biochemical variables. STUDY DESIGN: Clinical symptoms, genotype, and biochemical findings were analyzed retrospectively in 58 individuals with PA enrolled in the Inborn Errors of Metabolism Information System (IBEM-IS) based on the type of initial ascertainment: abnormal newborn screening (NBS), clinical presentation (symptomatic), or family history. RESULTS: The average age at initial evaluation and treatment was significantly younger in patients ascertained via abnormal NBS compared with those referred for clinical symptoms. Furthermore, the majority of individuals ascertained because of abnormal NBS were asymptomatic at diagnosis, compared with a minority of clinical presentations. A notable difference in the frequency of metabolic acidosis at initial presentation was observed between those with abnormal NBS (12.5%; 2 of 16) and those with an abnormal clinical presentation (79%; 19 of 24). The frequency of hyperammonemia was similar in the 2 groups. CONCLUSION: Our data support the continued value of NBS to identify individuals with PA, who are diagnosed and treated earlier than for other modes of ascertainment. There were no statistically significant correlations between genotype and NBS for C3 acylcarnitines. Although expanded use of NBS has allowed for early diagnosis and treatment, long-term outcomes of individuals with PA, especially with respect to mode of ascertainment, remain unclear and would benefit from a longitudinal study.

Exploratory application of the Ages and Stages (ASQ) child development screening test in a low-income Peruvian shantytown population.

OBJECTIVES: Public health research on child health is increasingly focusing on the long-term impacts of infectious diseases, malnutrition and social deprivation on child development. The objectives of this exploratory study were to (1) implement the Ages and Stages Questionnaires (ASQ) in children aged 3 months to 5 years in a low-income Peruvian population and (2) to correlate outcomes of the ASQ with risk factors such as nutritional status, diarrhoea incidence and wealth index. SETTING: Primary data collection was carried out in the Pampas de San Juan de Miraflores, a periurban low-income community in Lima, Peru. PARTICIPANTS: The study population included 129 children selected through community census data, with a mean age of 22 months (SD 6.8) and with almost equal gender distribution (51% males). INTERVENTION: A Peruvian psychologist administered the age-appropriate (ASQ2 for participants enrolled in 2009, ASQ3 for participants enrolled in 2010). Results of the ASQ are reported separately for five scales, including Communication, Gross Motor, Fine Motor, Problem Solving and Personal-Social. PRIMARY AND SECONDARY OUTCOME MEASURES: For each scale, results are reported as normal or suspect, meaning that some milestone attainment was not evident and further evaluation is recommended. RESULTS: Overall, 50 of 129 children (38.7%) had suspect results for at least one of the five scales, with the highest rates of suspect results on the Communication (15.5%) and Problem Solving scales (13.9%). Higher rates of suspect outcomes were seen in older children, both overall (p=0.06) and on Problem Solving (p=0.009), and for some scales there were trends between suspect outcomes and wealth index or undernutrition. CONCLUSIONS: The ASQ was successfully applied in a community-based study in a low-income Peruvian population, and with further validation, the ASQ may be an effective tool for identifying at-risk children in resource-poor areas of Latin America.

Ammonia control in children ages 2 months through 5 years with urea cycle disorders: comparison of sodium phenylbutyrate and glycerol phenylbutyrate.

OBJECTIVES: To examine ammonia levels, pharmacokinetics, and safety of glycerol phenylbutyrate (GPB; also referred to as HPN-100) and sodium phenylbutyrate (NaPBA) in young children with urea cycle disorders (UCDs). STUDY DESIGN: This open label switch-over study enrolled patients ages 29 days to under 6 years taking NaPBA. Patients underwent 24-hour blood and urine sampling on NaPBA and again on a phenylbutyric acid-equimolar dose of GPB and completed questionnaires regarding signs and symptoms associated with NaPBA and/or their UCD. RESULTS: Fifteen patients (8 argininosuccinate lyase deficiency, 3 argininosuccinic acid synthetase deficiency, 3 ornithine transcarbamylase deficiency, 1 arginase deficiency) ages 2 months through 5 years enrolled in and completed the study. Daily ammonia exposure (24-hour area under the curve) was lower on GPB and met predefined noninferiority criteria (ratio of means 0.79; 95% CI 0.593-1.055; P=.03 Wilcoxon; 0.07 t test). Six patients experienced mild adverse events on GPB; there were no serious adverse events or significant laboratory changes. Liver tests and argininosuccinic acid levels among patients with argininosuccinate lyase deficiency were unchanged or improved on GPB. Eleven of 15 patients reported 35 symptoms on day 1; 23 of these 35 symptoms improved or resolved on GPB. Mean systemic exposure to phenylbutyric acid, phenylacetic acid, and phenylacetylglutamine (PAGN) were similar and phenylacetic acid exposure tended to be higher in the youngest children on both drugs. Urinary PAGN concentration was greater on morning voids and varied less over 24 hours on GPB versus NaPBA. CONCLUSIONS: GPB results in more evenly distributed urinary output of PAGN over 24 hours were associated with fewer symptoms and offers ammonia control comparable with that observed with NaPBA in young children with UCDs.