Psychiatric manifestations of treatable hereditary metabolic disorders in adults

Abstract

Detecting psychiatric disorders of secondary origin is a crucial concern for the psychiatrist. But how can this reliably be done among a large number of conditions, most of which have a very low prevalence? Metabolic screening undertaken in a population of subjects with psychosis demonstrated the presence of treatable metabolic disorders in a significant number of cases. The nature of the symptoms that should alert the clinician is also a fundamental issue and is not limited to psychosis. Hereditary metabolic disorders (HMD) are a rare but important cause of psychiatric disorders in adolescents and adults, the signs of which may remain isolated for years before other more specific organic signs appear. HMDs that present purely with psychiatric symptoms are very difficult to diagnose due to low awareness of these rare diseases among psychiatrists. However, it is important to identify HMDs in order to refer patients to specialist centres for appropriate management, disease-specific treatment and possible prevention of irreversible physical and neurological complications. Genetic counselling can also be provided. This review focuses on three HMD categories: acute, treatable HMDs (urea cycle abnormalities, remethylation disorders, acute intermittent porphyria); chronic, treatable HMDs (Wilson’s disease, Niemann-Pick disease type C, homocystinuria due to cystathionine beta-synthase deficiency, cerebrotendinous xanthomatosis); and chronic HMDs that are difficult to treat (lysosomal storage diseases, X-linked adrenoleukodystrophy, creatine deficiency syndrome). We also propose an algorithm for the diagnosis of HMDs in patients with psychiatric symptoms.

Porphyria: often discussed but too often missed

“…These may begin with minor behaviour changes, such as anxiety, impatience or insomnia 18. Other features include severe depression, anhedonia, grandiose delusions and severe psychotic episodes, resembling symptoms more typically associated with schizophrenia.…”

Nosology and Phenomenology of Psychosis in Movement Disorders

“…In the first description of the disease, S.A. Kinnier Wilson described psychotic symptoms in 2 of 12 patients . Even though psychiatric disturbances have been reported in 50% to 70% of Wilson's disease (WD) patients, < 10% showed psychosis, suggesting that this manifestation is not a hallmark of the disease . On the other hand, psychotic symptoms at disease onset may be present in 35% of patients, with an interval between onset of psychosis and diagnosis of WD of 2.4 years .…”

Developmental Delay, Treatment-Resistant Psychosis, and Early-Onset Dementia in a Man With 22q11 Deletion Syndrome and Huntington’s Disease

“…This may be particularly important for people with long-standing psychiatric disorders who develop new signs and symptoms (e.g., dementia and a movement disorder as with EF). Although individually rare, dozens of single gene disorders can initially present with a clinical portrait confusable with idiopathic psychosis (38), and many are detected only when new neurological or medical symptoms develop.…”