DECREASE IN BENZODIAZEPINE RECEPTOR-BINDING IN A PATIENT WITH ANGELMAN SYNDROME DETECTED BY I-123 IOMAZENIL AND SINGLE-PHOTON EMISSION TOMOGRAPHY

A receptor mapping technique using iodine 123 iomazenil and single-pho ton emission tomography (SPET) was employed to examine benzodiazepine receptor binding in a patient with Angelman syndrome (AS). AS is chara cterized by developmental delay, seizures, inappropriate laughter and ataxic movement. In this entity there is a cytogenic deletion of the p roximal long arm of chromosome 15q11-q13, where the gene encoding the GABA(A) receptor beta 3 subunit (GABRB3) is located. Since the benzodi azepine receptor is constructed as a receptor-ionophore complex that c ontains the GABA(A) receptor, it is a suitable marker for GABA-ergic s ynapsis. To determine whether benzodiazepine receptor density, which i ndirectly indicates changes in GABA(A) receptor density, is altered in the brain in patients with AS, we investigated a 27-year-old woman wi th AS using I-123-iomazenil and SPET. Receptor density was quantitativ ely assessed by measuring the binding potential using a simplified met hod. Regional cerebral blood flow was also measured with N-isopropyl-p -[I-123]iodoampheramine. 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 pres ent study, we indirectly demonstrated the disturbance of inhibitory ne urotransmission mediated by the GABA(A) receptor in the investigated p atient. I-123-iomazenil with SPET was useful to map benzodiazepine rec eptors, which indicate GABA(A) receptor distribution and their density .