Hyperphenylalaninemia is a hereditary metabolic disorder that causes elevated blood phenylalanine (Phe). Hyperphenylalaninemias are classified as Phenylketonuria PKU (Phe > 6 mg/dL) or mild hyperphenylalaninemia (mHPA) (Phe 2–6 mg/dL). This study examines the cognitive functioning of early diagnosed children with mHPA compared with early diagnosed and treated children with PKU.

Psychomotor development (BSID-II) at 12 and 36 months of age, and cognitive performance at 4 and 7 years of age (WPPSI and WISC-R), were assessed in 118 PKU and 97 mHPA patients. Cognitive profile analysis of WISC-R subscales in school age children was performed and results were compared between the two groups.

Both groups preformed within the average range. Scores were significantly higher in the mHPA group. The mean Mental Development Index (MDI) at 12 months of age was 98.1 in the mHPA group and 92.3 in the PKU group ( p < 0.0002). At 36 months the MDI was 94.6 in the mHPA group and 84.7 in the PKU group ( p = 0.0001. At age four years the mean Full Scale IQ was 106.5 (mHPA group) and 95.9 (PKU group) ( p < 0.0001). At age seven years the mean Full Scale IQ was 100.9 (mHPA group) and 89.9 (PKU group) ( p < 0.005). The pattern of deficits was similar in both groups, with relative weaknesses in working memory and attention.

Children with mHPA achieved cognitive performance well within the average range and attained significantly higher scores than children with PKU. However, they appeared to have relative weaknesses in working memory and attention, similar to children with PKU.