(088) Initial psychotic episode in a patient with an inborn error of cobalamin metabolism methylcobalamin type cblG deficiency: A case report

Abstract:

Background: The relationship between neuropsychiatric disorders and cobalamin deficiency is well known, but little information is available on psychiatric complications of inborn errors of intracellular cobalamin metabolism. These patients present with developmental delay, seizures, dementia and psychosis, causing elevated levels of homocysteine and intrinsic vitamin B12 deficiency (Watkins, 2011). In this report, we describe the manifestations and successful psychiatric treatment of a patient with an inborn error of cobalamin metabolism.

Case: Mr. W is a 23-year-old male with cobalamin G defect, who was hospitalized for encephalopathy and hallucinations. Notable past medical history includes chronic kidney disease, seizures, intellectual disability, and hypothyroidism. He has no significant past psychiatric history. Due to the COVID-19 pandemic, the patient was increasingly isolated. Psychosis began with disorganized thoughts, progressing to delusions and eventually both auditory and visual hallucinations. Other notable exam findings include blunted affect and psychomotor retardation. Homocysteine levels were elevated from baseline. Cerebrospinal fluid showed elevated protein levels with the presence of 3-0-meythldopa. Risperidone was initiated, then switched to olanzapine due to reported side effects with persistence of psychosis. He was switched from olanzapine to aripiprazole after cross-titration and optimized on aripiprazole 10mg nightly, leading to a resolution in his psychiatric symptoms.

Discussion: Mr. W’s increased isolation may have led to increased stress, which has been associated with high levels of homocysteine in the literature (Gun Kang, 2005). Elevated homocysteine is reported in individuals with neuropsychiatric disorders (Moustafa, 2014). Additionally, high levels of homocysteine are linked with inflammatory bio-makers (Li, 2015). Aripiprazole and risperidone have been shown to decrease inflammatory biomarkers in patients with psychosis (Juncal-Ruiz, 2018).

Conclusion: Patients with inborn errors of cobalamin metabolism have increased levels of homocysteine, which is associated with an inflammatory response and neuropsychiatric disorders. We recommend that psychosis in patients with an inborn error of cobalamin metabolism be initially treated with risperidone, and aripiprazole as a second-line treatment.

References:
1. Watkins, D. & Rosenblatt, D. S. Inborn errors of cobalamin absorption and metabolism. American Journal of Medical Genetics 2011:157:33-44.
2. Gun Kang, M. et al. Job stress and cardiovascular risk factors in male workers. Preventive Medicine 2005;40:583-588.
3. Moustafa, A. et al. Homocysteine levels in schizophrenia and affective disorders—focus on cognition. Front Behav Neurosci 2014;8:343.
4. Li, T. et al. Serum Homocysteine Concentration Is Significantly Associated with Inflammatory/Immune Factors. PLOS ONE 2015;10:e0138099.
5. Juncal-Ruiz, M. et al. Comparison of the anti-inflammatory effect of aripiprazole and risperidone in 75 drug-naïve first episode psychosis individuals: A 3 months randomized study. Schizophrenia Research 2018;202:226-233.

Learning Objectives:
1. Describe the relationship between metabolic cobalamin deficiency and psychosis.
2. Question the role of transient biomarker elevation and psychosis.
3. Assess the treatment considerations for patients with metabolic cobalamin deficiency.