Onset of psychiatric signs and impaired neurocognitive domains in inherited metabolic disorders: A case series

François Medjkane, Marine Bohet, Marielle Ister, David Cohen, Aesa Parenti, Majda Janati, Karine Mention, Dries Dobbelaere, Renaud Jardri

Research output: Contribution to journalArticlepeer-review


Inherited metabolic disorders (IMDs) can present with psychiatric signs that vary widely from one disease to another. This picture is further complicated by the fact that these features occur at very different illness time points, which may further delay appropriate diagnosis and treatment. In this case series of 62 children and adolescents suffering from IMDs, we clustered psychiatric signs (on the basis of the fifth edition of the Diagnostic and Statistical Manual for Mental Disorders classification) as well as impaired cognitive domains (on the basis of the Research Domain Criteriamatrix) according to their mean age of onset (5.7 ± 4 years). We observed consistent patterns of occurrence across disorders. Externalizing symptoms, sleep problems, and cross-domain self-regulation deficits were found to precede the IMD diagnosis. Repetitive thoughts and behaviors as well as emotional dysregulation were found to occur around the disease onset. Finally, late-onset features included dissociative or eating disorders, together with impaired emotion knowledge. Clinicians should specifically look for the co-occurrence of age-specific atypical signs, such as treatment resistance or worsening with psychotropic medication in the earliest stages and symptom fluctuation, confusion, catatonia, or isolated visual hallucinations. We believe that the combined characterizations of psychiatric signs and impaired neurocognitive domains may enable the earliest detection of IMDs and the appropriate care of these particular manifestations. Key Points: Psychiatric signs are common in inherited metabolic disorders (IMDs) and may occur in the same age-range as other clinical manifestations. Three clusters of psychiatric signs and two clusters of neurocognitive domains can be defined according to their mean age of onset. Warning signs to be used in liaison psychiatry should include age-specific cognitive impairments.

Original languageEnglish
Pages (from-to)29-36
Number of pages8
JournalJIMD Reports
Issue number1
StatePublished - 1 Mar 2021
Externally publishedYes


  • DSM
  • RDoC
  • cognition
  • development
  • psychiatry
  • rare disease


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