Predictability and inconsistencies in the cognitive outcome of early treated PKU patients

Filippo Manti, Francesca Nardecchia, Sabrina Paci, Flavia Chiarotti, Claudia Carducci, Carla Carducci, Silvia Dalmazzone, Graziella Cefalo, Elisabetta Salvatici, Giuseppe Banderali, Vincenzo Leuzzi

Research output: Contribution to journalArticlepeer-review


Long-term cognitive outcome and treatment of adult early treated (ET)PKU patients is a main issue in PKU research. We questioned whether the intellectual development of ETPKU patients is stable and to what extent its variation may be predicted by the quality of metabolic control. The aims of the present longitudinal retrospective study were to assess in young adult ETPKU patients: i) the relationship between IQ and metabolic control during the first two decades of life; and ii) the intra- and interindividual variability in the developmental trajectory which cannot be predicted by the disease’s biomarkers. We collected biochemical data from 65 ETPKU patients (diagnostic blood Phe > 360 μmol/l) who were assessed twice for IQ (Wechsler Intelligence Scale) during their lifetime (mean age: 10.2 and 19.6 years, respectively). Results show that in ETPKU patients IQ over the second decade of life remained stable in about half of the patients (51%); while the rest experienced a gain (7 to 15 points) or loss (7 to 28 points) in IQ scores (23 and 26% respectively) whatever the quality of metabolic control was. The main factor affecting the second IQ was the value of the first IQ (p < 0.000) whose effect overruled that of the markers of metabolic control. Looking at the developmental trajectory of our ETPKU patients, the present study disclosed a remarkable interindividual variability in their cognitive outcome and also an inconsistent linkage between cognitive performances and biochemical control, thus supporting the hypothesis of an individual resilience or vulnerability to Phe in young adult ETPKU.

Original languageEnglish
Pages (from-to)793-799
Number of pages7
JournalJournal of Inherited Metabolic Disease
Issue number6
Publication statusPublished - Nov 1 2017


  • Cognition
  • Intellectual disabilities
  • Phenylketonurias

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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