Cobalamin C Deficiency, an Inborn Error of Metabolism presenting with Subacute Neuropsychiatric Symptoms
Sarah Engel1, Salman Rashid1, Ali Beshri2, Amitha Ananth1
1Department of Pediatrics, Division of Neurology, 2Department of Genetics, University of Alabama Birmingham
Objective:
Inpatient Neurology teams are often consulted to rule out neurological causes for new-onset neuropsychiatric symptoms. This case highlights the importance of considering possible Inborn Errors of Metabolism (IEM) that require specific treatments, and avoiding premature closure on a primary psychiatric disorder.
Background:
A 15-year-old presented to a pediatric hospital with a 4-8 week onset of neuropsychiatric (psychosis, psychomotor slowing, catatonia, sleep cycle irregularities, and tremors) and systemic (acute on chronic kidney injury and hypertension) symptoms. Neurology was consulted for further evaluation. In addition to the abnormal higher mental function exam, the neurological exam was significant for hyperreflexia in both the upper and lower extremities.
Results:
Neuroimaging (an initial non-contrast CT Head and MRI brain with and without contrast) did not reveal an intracranial abnormality. Analysis of cerebrospinal fluid, including an autoimmune encephalitis panel, was unremarkable. Metabolic testing was significant for elevated homocysteine and methylmalonic aciduria with normal Vitamin B12 levels. Genetics and metabolic consult recommended testing for Cobalamin C deficiency that returned positive with pathogenic mutations in MMACHC gene. Neuropsychiatric symptoms began to improve after the initiation of treatment with hydroxocobalamin, carnitine, betaine, and leucovorin.
Conclusions:
Cobalamin C deficiency (CblC) most commonly presents in infants less than 1 year, but is also known to present rarely in adolescence or adulthood, most commonly with subacute onset psychiatric symptoms, myelopathy, and cardiovascular disease. CblC is an autosomal recessive disorder caused most commonly by pathogenic variants within the MMACHC gene. Late-onset forms of IEM can present with isolated neuropsychiatric symptoms years after birth and thus are prone to be missed. Treatable metabolic disorders should be considered in the workup for new-onset neuropsychiatric symptoms.