Serial Magnetic Resonance Imaging and ¹H-Magnetic Resonance Spectroscopy in GABA Transaminase Deficiency: A Case Report

Abstract

Gamma-aminobutyric acid transaminase (GABA-T) deficiency is a rare, autosomal recessive disorder characterized by severe psychomotor retardation, early-onset epileptic encephalopathy, intractable seizures, hypotonia, and hyperreflexia. The disease is caused by mutation in the 4-aminobutyrate aminotransferase (ABAT) gene, which encodes an enzyme involved in GABA catabolism. In this chapter, a 10-year follow-up of GABA-T deficiency in a rare case of a long-term survivor patient is discussed. The patient showed a progression of clinical phases with increasing age. In infancy, the patient developed psychomotor retardation and recurrent encephalopathic episodes associated with febrile illness. In early childhood, the patient presented with refractory involuntary and hyperkinetic movements and dystonic hypertonicity. In childhood, the patient gradually progressed into the chronic stable phase of the condition. Magnetic resonance imaging demonstrated high signal intensity on diffusion-weighted images involving the internal and external capsules and cerebral white matter in infancy which disappeared gradually by the age of 3 years, and showed subsequently diffuse brain atrophy in childhood. Using proton magnetic resonance spectroscopy, GABA levels in the basal ganglia were shown to be markedly elevated at the age of 1–2 years, and subsequently decreased with increasing age (toward 5 years). These findings suggest that the encephalopathic episodes in infancy and clinical severity of involuntary and hyperkinetic movements may be correlated with levels of GABA in the basal ganglia. The high levels of GABA in the cerebrospinal fluid remained unaltered, whereas levels of GABA in the serum decreased during childhood. Further investigation of long-term clinical surveillance may improve the understanding of GABA-T deficiency.

Appendices

Authors’ Contributions

K.I. wrote the manuscript and provided medical care for the patient; Y.T. and M.T. provided medical care for the patient; M.T. performed the analysis of magnetic resonance spectroscopy and interpreted the results; N.A. interpreted magnetic resonance images; T.G. approved the final manuscript. All authors read and approved the final version of the manuscript.

Corresponding Author

Kazushi Ichikawa.

Conflict of Interest

Kazushi Ichikawa, Megumi Tsuji, Yu Tsuyusaki, Moyoko Tomiyasu, Noriko Aida, and Tomohide Goto declare that they have no conflict of interest.

Funding

Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant Number 26461843) [Aida, Goto, Tsuyusaki].

Compliance with Ethics Guideline

Informed Consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from the patient’s parents for being included in the study.