Decrease in benzodiazepine receptor binding in a patient with Angelman syndrome detected by iodine-123 iomazenil and single-photon emission tomography

A receptor mapping technique using iodine-123 iomazenil and single-photon emission tomography (SPET) was employed to examine benzodiazepine receptor binding in a patient with Angelman syndrome (AS). AS is characterized by developmental delay, seizures, inappropriate laughter and ataxic movement. In this entity there is a cytogenic deletion of the proximal long arm of chromosome 15g11–q13, where the gene encoding the GABA_A receptor3 subunit (GABRB3) is located. Since the benzodiazepine receptor is constructed as a receptor-ionophore complex that contains the GABA_A receptor, it is a suitable marker for GABA-ergic synapsis. To determine whether benzodiazepine receptor density, which indirectly indicates changes in GABA_A receptor density, is altered in the brain in patients with AS, we investigated a 27-year-old woman with AS using¹²³I-iomazenil and SPET. Receptor density was quantitatively assessed by measuring the binding potential using a simplified method. Regional cerebral blood flow was also measured withN-isopropyl-p-¹²³I]iodoamphetamine. We demonstrated that benzodiazepine receptor density is severely decreased in the cerebellum, and mildly decreased in the frontal and temporal cortices and basal ganglia, a result which is considered to indicate decreased GABA_A receptor density in these regions. Although the deletion of GABRB3 was not observed in the present study, we indirectly demonstrated the disturbance of inhibitory neurotransmission mediated by the GABA_A receptor in the investigated patient.¹²³I-iomazenil with SPET was useful to map benzodiazepine receptors, which indicate GABA_A receptor distribution and their density.