First-year metabolic control guidelines and their impact on future metabolic control and neurocognitive functioning in children with PKU

Abstract

There is a consensus on the importance of early and life-long treatment for PKU patients. Still, differences exist on target blood phenylalanine (Phe) concentrations for children with PKU in different countries and treatment centers. For the first time, long-term metabolic control and child development and cognitive functioning is compared between children with mean phenylalanine concentrations under 240 μmol/L (group A), between 240 and 360 μmol/L (group B) or over 360 μmol/L (group C) during their first year of life. METHODS: 70 patients diagnosed with PKU through neonatal screening with Phe > 900 μmol/L, were divided into 3 groups: A, B and C, according to mean Phe concentrations and standard deviation (SD). Metabolic control during childhood, psychomotor development and IQ were compared. RESULTS: In group A, Phe was maintained within the recommended range until 6 years of age, in Group B, until 3 years of age, and in group C, Phe was always over the recommended range. No significant differences were found between the three groups in mental development index (MDI) and motor development index (PDI) scores at 12, 24, and 30 months of age, but group C had the lowest scores on MDI at all age periods. At preschool and school age, IQ was higher in group A compared to group C. CONCLUSION: Results show that mean blood Phe concentrations between 120 and 240 μmol/L during first year of life have a positive impact in metabolic control and cognitive functioning during childhood.

Update on Dietary Compliance, Nutritional Status, and Neuropsychological Functioning in the Chilean Phenylketonuria cohort

“…Therefore, keeping Phe levels under 360 umol/L, avoiding fluctuations, will favor the correct neuropsychological functioning of individuals with PKU. [40,44] More that 80% of the sample had neuropsychologial functioning within the normal range, likely a result of good Phe level control.…”

Factors that increase risk for poor adherence to phenylketonuria treatment in Brazilian patients

“…A sample of the lifetime Phe of adolescents and adults, corresponding to the annual median Phe levels from the first 12 years of life, was averaged to obtain the childhood Phe level variable. The SD of lifetime and childhood Phe levels were also obtained to determine fluctuation rates (Anastasoaie et al, 2008; De la Parra et al, 2017; Hood et al, 2014; Palermo et al, 2017; Vilaseca et al, 2010). The current patient's blood Phe level was represented by the median Phe level over the 12 months prior to participation.…”

Motor control and learning in individuals with early-treated phenylketonuria.

“…Results of previous studies on motor control and ETPKU are mixed but generally suggest an impairment in arm/hand dexterity and fine motor control (for reviews, see Hofman et al, 2018; Janzen & Nguyen, 2010; Moyle et al, 2007). In terms of toddlers and young children with ETPKU, whereas some studies of young children have reported ETPKU-related impairments in motor development (e.g., Arnold et al, 1998; Beblo et al, 2007; Nazi et al, 2013), others have failed to find evidence of a delay (e.g., Brandalize & Czeresnia, 2004; de la Parra et al, 2017; Wu et al, 2011).…”