Child Neurology: Creatine Biosynthesis Disorder in an Adolescent With Capgras Syndrome and Reduplicative Paramnesia

This case report and discussion pertain to a 17-year-old female patient with developmental delay and acute onset of psychosis, diagnosed with guanidinoacetate methyltransferase (GAMT) deficiency, a rare creatine biosynthesis disorder. The patient experienced auditory hallucinations, paranoia, and delusional misidentification syndromes (Capgras syndrome and reduplicative paramnesia), following a viral respiratory illness. The neurologic examination was nonfocal but included intermittent negative myoclonus, generalized stiff movements, and a mechanical gait, which initially suggested catatonia or autoimmune encephalitis. MRI of the brain was normal, as was her CSF profile, although EEG revealed diffuse slowing with frequent generalized spike waves. Sequential empiric treatments for catatonia and autoimmune encephalitis provided limited benefit. Subsequent biochemical and genetic testing confirmed GAMT deficiency, supported by a markedly decreased creatine peak on MR spectroscopy of the brain. This case highlights GAMT deficiency as a consideration in young patients with neuropsychiatric symptoms, particularly psychosis with atypical motor findings and a history of developmental delay. The rare presentation of delusional misidentification symptoms expands the spectrum of clinical findings described in patients with GAMT deficiency, a rare disorder reported in at least 130 individuals to date. Treatment with creatine and ornithine supplementation led to marked improvement, returning her incrementally toward baseline functioning. This case broadens the understanding of GAMT deficiency's phenotypic range and underscores the importance of metabolic testing in tandem with or closely following empiric but unsuccessful treatment trials, even when the initial clinical presentation suggests primary psychiatric, autoimmune, or inflammatory etiologies.