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Diagnostic and treatment implications of psychosis secondary to treatable metabolic disorders in adults: a systematic review.

Bonnot O, Klünemann HH, Sedel F, Tordjman S, Cohen D, Walterfang M - Orphanet J Rare Dis (2014)

Bottom Line: In general, published reports did not provide explicit descriptions of psychiatric symptoms.The literature search findings are presented with a didactic perspective, showing key features for each disease and psychiatric signs that should trigger psychiatrists to suspect that psychotic symptoms may be secondary to an IEM.IEMs with a psychiatric presentation and a lack of, or sub-clinical, neurological signs are rare, but should be considered in patients with atypical psychiatric symptoms.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Child and Adolescent Psychiatry, Centre Hospitalier Universitaire de Nantes, Hôpital Mère-Enfant, 7 quai Moncousu, 44 000 Nantes, France. olivier.bonnot@chu-nantes.fr.

ABSTRACT

Objective: It is important for psychiatrists to be aware of certain inborn errors of metabolism (IEMs) as these rare disorders can present as psychosis, and because definitive treatments may be available for treating the underlying metabolic cause. A systematic review was conducted to examine IEMs that often present with schizophrenia-like symptoms.

Data sources: Published literature on MEDLINE was assessed regarding diseases of homocysteine metabolism (DHM; cystathionine beta-synthase deficiency [CbS-D] and homocysteinemia due to methyltetrahydrofolate reductase deficiency [MTHFR-D]), urea cycle disorders (UCD), acute porphyria (POR), Wilson disease (WD), cerebrotendinous-xanthomatosis (CTX) and Niemann-Pick disease type C (NP-C).

Study selection: Case reports, case series or reviews with original data regarding psychiatric manifestations and cognitive impairment published between January 1967 and June 2012 were included based on a standardized four-step selection process.

Data extraction: All selected articles were evaluated for descriptions of psychiatric signs (type, severity, natural history and treatment) in addition to key disease features.

Results: A total of 611 records were identified. Information from CbS-D (n = 2), MTHFR-D (n = 3), UCD (n = 8), POR (n = 12), WD (n = 11), CTX (n = 14) and NP-C publications (n = 9) were evaluated. Six non-systematic literature review publications were also included. In general, published reports did not provide explicit descriptions of psychiatric symptoms. The literature search findings are presented with a didactic perspective, showing key features for each disease and psychiatric signs that should trigger psychiatrists to suspect that psychotic symptoms may be secondary to an IEM.

Conclusion: IEMs with a psychiatric presentation and a lack of, or sub-clinical, neurological signs are rare, but should be considered in patients with atypical psychiatric symptoms.

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Related in: MedlinePlus

Diagnostic algorithm for diagnosing inborn errors of metabolism in patients with schizophrenia-like symptoms. Negative: If exams are negative and suspicion is high. Positive: Could lead to diagnoses or high suspicion of specific disease. MRI = magnetic resonance imaging; MTHFR-CbS = methylenetetrahydrofolate reductase-cystathionine beta-synthase; NP-C = Niemann-Pick disease type C; UCDs = urea cycle disorders, WD = Wilson disease.
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Figure 2: Diagnostic algorithm for diagnosing inborn errors of metabolism in patients with schizophrenia-like symptoms. Negative: If exams are negative and suspicion is high. Positive: Could lead to diagnoses or high suspicion of specific disease. MRI = magnetic resonance imaging; MTHFR-CbS = methylenetetrahydrofolate reductase-cystathionine beta-synthase; NP-C = Niemann-Pick disease type C; UCDs = urea cycle disorders, WD = Wilson disease.

Mentions: The second major difficulty is to recognize IEMs and to think about an organic etiology in clinical practice. In order to help psychiatrists, it could be clinically useful to identify psychiatric features that may trigger for the search of organic disorder in patients with schizophrenia. Unfortunately, data regarding organic psychosis and its specific associated symptoms are scarce. One study, which was not specific for IEMs, analyzed the phenomenology of 74 patients with ‘organic schizophrenia’ compared with ‘non-organic schizophrenia’ [144]. Visual hallucinations and confusion were seen more often among patients with organic schizophrenia, and comparable features have been observed in elderly schizophrenia patients [145,146]. A handful of inborn errors of metabolism may cause elementary hallucination and visual hallucinations which are associated with various organic and psychiatric conditions [147]. Hallucinations are a core symptom of schizophrenia and are more often auditory or at least, auditory hallucinations are more important than visual hallucinations. We suggest therefore that predominant visual hallucinations are highly suggestive of organic disorders such as IEM. An acute onset of psychiatric symptoms may also raise suspicion of IEMs (e.g. UCDs, porphyria or homocysteinemia with CbS-D). It is also notable that data indicate a high degree of association of catatonia with organic disorders, especially if it occurs during childhood or adolescence [148]. An unusually high proportion of patients with organic disorders has been reported in large series of patients with early-onset schizophrenia, which suggests that an early-onset of schizophrenia-like symptoms is another indicator for possible organic origin of disease, especially if associated with progressive cognitive decline, which is a common feature in IEMs [149]. Finally, treatment resistance is frequently associated with IEMs [150], again suggesting its possible use as an indicator for possible organic disease. In summary, we may suggest six readily recognizable features that should trigger the suspicion of organicity associated with schizophrenia-like symptoms: 1) acute confusion; 2) visual hallucinations more important than auditory hallucinations; 3) catatonia; 4) progressive cognitive decline; 5) early or acute onset and; 6) treatment resistance (see Table 1). As the validity and specificity of these atypical psychiatric signs have not yet been evaluated, they are presented to raise awareness and suggest clinical and neurological exams prior to further progressive screening. Both atypical psychiatric signs and main clinical/biomarker features of IEM lead us to propose an algorithm (see Figure 2). This algorithm is based on clinical practice of OB, HK and MW and DC. We plan to study his validity and reliance in further study in population of patients with psychiatric signs and IEM. Further research is needed to develop a real suspicion index from our group of atypical psychiatric signs associated with this algorithm.


Diagnostic and treatment implications of psychosis secondary to treatable metabolic disorders in adults: a systematic review.

Bonnot O, Klünemann HH, Sedel F, Tordjman S, Cohen D, Walterfang M - Orphanet J Rare Dis (2014)

Diagnostic algorithm for diagnosing inborn errors of metabolism in patients with schizophrenia-like symptoms. Negative: If exams are negative and suspicion is high. Positive: Could lead to diagnoses or high suspicion of specific disease. MRI = magnetic resonance imaging; MTHFR-CbS = methylenetetrahydrofolate reductase-cystathionine beta-synthase; NP-C = Niemann-Pick disease type C; UCDs = urea cycle disorders, WD = Wilson disease.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4043981&req=5

Figure 2: Diagnostic algorithm for diagnosing inborn errors of metabolism in patients with schizophrenia-like symptoms. Negative: If exams are negative and suspicion is high. Positive: Could lead to diagnoses or high suspicion of specific disease. MRI = magnetic resonance imaging; MTHFR-CbS = methylenetetrahydrofolate reductase-cystathionine beta-synthase; NP-C = Niemann-Pick disease type C; UCDs = urea cycle disorders, WD = Wilson disease.
Mentions: The second major difficulty is to recognize IEMs and to think about an organic etiology in clinical practice. In order to help psychiatrists, it could be clinically useful to identify psychiatric features that may trigger for the search of organic disorder in patients with schizophrenia. Unfortunately, data regarding organic psychosis and its specific associated symptoms are scarce. One study, which was not specific for IEMs, analyzed the phenomenology of 74 patients with ‘organic schizophrenia’ compared with ‘non-organic schizophrenia’ [144]. Visual hallucinations and confusion were seen more often among patients with organic schizophrenia, and comparable features have been observed in elderly schizophrenia patients [145,146]. A handful of inborn errors of metabolism may cause elementary hallucination and visual hallucinations which are associated with various organic and psychiatric conditions [147]. Hallucinations are a core symptom of schizophrenia and are more often auditory or at least, auditory hallucinations are more important than visual hallucinations. We suggest therefore that predominant visual hallucinations are highly suggestive of organic disorders such as IEM. An acute onset of psychiatric symptoms may also raise suspicion of IEMs (e.g. UCDs, porphyria or homocysteinemia with CbS-D). It is also notable that data indicate a high degree of association of catatonia with organic disorders, especially if it occurs during childhood or adolescence [148]. An unusually high proportion of patients with organic disorders has been reported in large series of patients with early-onset schizophrenia, which suggests that an early-onset of schizophrenia-like symptoms is another indicator for possible organic origin of disease, especially if associated with progressive cognitive decline, which is a common feature in IEMs [149]. Finally, treatment resistance is frequently associated with IEMs [150], again suggesting its possible use as an indicator for possible organic disease. In summary, we may suggest six readily recognizable features that should trigger the suspicion of organicity associated with schizophrenia-like symptoms: 1) acute confusion; 2) visual hallucinations more important than auditory hallucinations; 3) catatonia; 4) progressive cognitive decline; 5) early or acute onset and; 6) treatment resistance (see Table 1). As the validity and specificity of these atypical psychiatric signs have not yet been evaluated, they are presented to raise awareness and suggest clinical and neurological exams prior to further progressive screening. Both atypical psychiatric signs and main clinical/biomarker features of IEM lead us to propose an algorithm (see Figure 2). This algorithm is based on clinical practice of OB, HK and MW and DC. We plan to study his validity and reliance in further study in population of patients with psychiatric signs and IEM. Further research is needed to develop a real suspicion index from our group of atypical psychiatric signs associated with this algorithm.

Bottom Line: In general, published reports did not provide explicit descriptions of psychiatric symptoms.The literature search findings are presented with a didactic perspective, showing key features for each disease and psychiatric signs that should trigger psychiatrists to suspect that psychotic symptoms may be secondary to an IEM.IEMs with a psychiatric presentation and a lack of, or sub-clinical, neurological signs are rare, but should be considered in patients with atypical psychiatric symptoms.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Child and Adolescent Psychiatry, Centre Hospitalier Universitaire de Nantes, Hôpital Mère-Enfant, 7 quai Moncousu, 44 000 Nantes, France. olivier.bonnot@chu-nantes.fr.

ABSTRACT

Objective: It is important for psychiatrists to be aware of certain inborn errors of metabolism (IEMs) as these rare disorders can present as psychosis, and because definitive treatments may be available for treating the underlying metabolic cause. A systematic review was conducted to examine IEMs that often present with schizophrenia-like symptoms.

Data sources: Published literature on MEDLINE was assessed regarding diseases of homocysteine metabolism (DHM; cystathionine beta-synthase deficiency [CbS-D] and homocysteinemia due to methyltetrahydrofolate reductase deficiency [MTHFR-D]), urea cycle disorders (UCD), acute porphyria (POR), Wilson disease (WD), cerebrotendinous-xanthomatosis (CTX) and Niemann-Pick disease type C (NP-C).

Study selection: Case reports, case series or reviews with original data regarding psychiatric manifestations and cognitive impairment published between January 1967 and June 2012 were included based on a standardized four-step selection process.

Data extraction: All selected articles were evaluated for descriptions of psychiatric signs (type, severity, natural history and treatment) in addition to key disease features.

Results: A total of 611 records were identified. Information from CbS-D (n = 2), MTHFR-D (n = 3), UCD (n = 8), POR (n = 12), WD (n = 11), CTX (n = 14) and NP-C publications (n = 9) were evaluated. Six non-systematic literature review publications were also included. In general, published reports did not provide explicit descriptions of psychiatric symptoms. The literature search findings are presented with a didactic perspective, showing key features for each disease and psychiatric signs that should trigger psychiatrists to suspect that psychotic symptoms may be secondary to an IEM.

Conclusion: IEMs with a psychiatric presentation and a lack of, or sub-clinical, neurological signs are rare, but should be considered in patients with atypical psychiatric symptoms.

Show MeSH
Related in: MedlinePlus