Neuropsychiatric comorbidities in adults with phenylketonuria: A retrospective cohort study

Deborah A. Bilder, Joyce A. Kobori, Jessica L. Cohen-Pfeffer, Erin M. Johnson, Elaina R. Jurecki, Mitzie L. Grant

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74 Scopus citations


Adults with phenylketonuria (PKU) may experience neurologic and psychiatric disorders, including intellectual disability, anxiety, depression, and neurocognitive dysfunction. Identifying the prevalence and prevalence ratios of these conditions will inform clinical treatment. This nested, case-controlled study used International Classification of Diseases, Ninth Revision (ICD-9) codes from the MarketScan® insurance claims databases from 2006 to 2012 and healthcare claims data for US-based employer and government-sponsored health plans. Prevalence and prevalence ratio calculations of neuropsychiatric comorbidities for adults (≥ 20 years old) with PKU were compared with two groups [diabetes mellitus (DM) and general population (GP)] matched by age, gender, geographic location, and insurance type. Age cohorts (i.e., 20–29, 30–39, 40–49, 50–59, 60–69, and 70 + years, and a combined subset of 20–39) were used to stratify data. The PKU cohort experienced significantly higher rates of several comorbid neurologic, psychiatric and developmental conditions. Compared to GP, PKU was associated with significantly higher prevalence for numerous neuropsychiatric conditions, most notably for intellectual disability (PR = 7.9, 95% CI: 6.4–9.9), autism spectrum disorder (PR = 6.1, 95% CI: 3.6–10.4), Tourette/tic disorders (PR = 5.4, 95% CI: 2.1–14.1), and eating disorders (4.0, 95% CI: 3.2–5.0). Rates of fatigue/malaise, epilepsy/convulsions, sleep disturbance, personality disorders, phobias, psychosis, and migraines among those with PKU exceeded rates for the GP but were comparable to those with DM, with significantly lower rates of concomitant disorders occurring in younger, compared to older, adults with PKU. Lifelong monitoring and treatment of co-occurring neuropsychiatric conditions are important for effective PKU management.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalMolecular Genetics and Metabolism
Issue number1
StatePublished - May 2017
Externally publishedYes


  • Comorbidity
  • Neurodevelopmental
  • Neurologic
  • Neuropsychiatric
  • Phenylalanine hydroxylase deficiency
  • Phenylketonuria


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