Case report A boy with a severe phenotype of succinic semialdehyde dehydrogenase deficiency Yoko Yamakawa a,b,⇑ , Tomoyuki Nakazawa a , Asuka Ishida a , Nobutomo Saito a , Mitsutaka Komatsu a , Tomoyo Matsubara a , Kaoru Obinata a , Shinichi Hirose c , Akihisa Okumura b , Toshiaki Shimizu b a Department of Pediatrics, Juntendo University, Urayasu Hospital, Japan b Department of Pediatrics, Juntendo University, School of Medicine, Japan c Department of Pediatrics, Fukuoka University, School of Medicine, Japan Received 20 December 2010; received in revised form 4 May 2011; accepted 6 May 2011 Abstract Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder affecting c-aminobutyric acid degradation. We describe here a boy with a severe phenotype of SSADH deficiency. He was referred because of a developmental delay at 4 months of age. At the age of 8 months, severe seizures developed. The diagnosis of SSADH deficiency was confirmed by an increase in 4-hydroxybutyric acid and heteroallelic mutation in the ALDH5A1 gene. His seizures were successfully treated with high-dose phenobarbital, and the electroencephalogram (EEG) abnormalities were ameliorated. However, the patient showed a degenerative clinical course with severe neurological deficits. A magnetic resonance imaging (MRI) scan revealed abnormal high intensities in the putamina and caudate nuclei on T2-weighted images, followed by marked atrophic changes. The clinical manifes- tation of our patient indicates the wide variety of SSADH deficiency phenotypes. Ó 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. 1. Introduction Succinic semialdehyde dehydrogenase (SSADH) defi- ciency is a rare autosomal recessive disorder affecting the degradation of c-aminobutyric acid (GABA). SSADH works with GABA transaminase to converts GABA to succinate. In the absence of SSADH, GABA is not broken down into succinic acid, but is converted into c-hydroxybutyric acid (GHB). It is unclear whether elevated GABA, GHB, or another neurometabolic change accounts for the phenotype, but the primary metabolic abnormality is an excessive concentration of GHB in the physiological fluids, with elevations up to 800-fold in the plasma and 1200-fold in the cerebrospi- nal fluid [1]. The SSADH gene (ALDH5A1) has been mapped to chromosome 6p22. More than 350 patients with SSADH deficiency have been identified worldwide. In Japan, Ishiguro et al. [2] reported the first patient in 2001, and since then, only a few patients have been reported. SSADH deficiency often presents in childhood with non-specific clinical manifestations. The most common neurological symptoms include language delay, ataxia, hypotonia, and mental retardation. Seizures are less common, occurring in about half of all patients [3]. Although SSADH deficiency does not generally mani- fest as a degenerative condition, developmental regres- 0387-7604/$ - see front matter Ó 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.braindev.2011.05.003 ⇑ Corresponding author. Address: Department of Pediatrics, Junt- endo University, School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Tel.: +81 3 3813 3111; fax: +81 3 5800 1580. E-mail address: yooyoo@juntendo.ac.jp (Y. Yamakawa). www.elsevier.com/locate/braindev Brain & Development 34 (2012) 107–112