Recurrent psychiatric manifestations in thiamine‐responsive megaloblastic anemia syndrome due to a novel mutation c.63_71 delACCGCTC in the gene SLC19A2

Abstract

Thiamine-responsive megaloblastic anemia syndrome (TRMA) is a recessive condition that mainly manifests as megaloblastic anemia, hearing loss, and diabetes.1, 2 It is caused by mutations in the gene SLC19A2, which codes for a high-affinity thiamine transporter.3 Our male proband had sensorineural deafness diagnosed at 4 years of age and insulin-dependent diabetes diagnosed at 5 years. At 19 he was found to have myopia, astigmatism and decreased peripheral visual fields, as well as megaloblastic anemia with low serum thiamine level. He was started on 100 mg thiamine daily, which was later decreased to 50 mg. The proband's brother had similar features. He died at 18 years, reportedly from a heart problem. The proband had a history of inappropriate sexual behavior since the age of 13 and a long history of explosive/aggressive/assaulting behavior and transient paranoid ideations. Aggressive behavior was triggered by frustration around food items and by misperceptions and beliefs that others were ‘bad-mouthing’ him. He communicated through sign language and a few spontaneous verbalizations and was oriented x3. Irritable mood, impulsivity, and paranoid ideations were noted. Insight was impaired and judgment was fair for his mental age. A gradual decline from low–normal to mild intellectual disability was noted. Thiamine treatment during 18 months substantially decreased the frequency and severity of his explosive/aggressive episodes but did not affect his transient paranoid ideations. Multiple psychotropic medications were previously ineffective at controlling these episodes. Testing for mutations in SLC19A2 revealed homozygosity for the c.63_71delACCGCTC mutation, resulting in a frameshift and truncated protein. This mutation was not previously reported.2 To our knowledge, one other patient with TRMA and a psychotic episode was previously reported.4 This female patient had only one documented psychotic episode with mood changes. Neuropsychological manifestations related to thiamine deficiency have been well established in alcoholic populations known for nutrient deficits.5 Thiamine administration controlled the progressive encephalopathy and the explosive/aggressive behavior in our patient, but his recurrent mood disorder with paranoid ideations did not resolve with thiamine supplementation. In addition to the thiamine deficiency, the novel SLC19A2 mutation reported here may have contributed to the patient's psychotic manifestations by an unknown mechanism. No conflict of interest is reported for any of the authors. This report was partially supported by The Office of People with Developmental Disabilities of New York State. The sponsor did not have any role in the conducting or the reporting of the study. Consent was obtained from the patient's legal guardian.