Succinic Semialdehyde Dehydrogenase Deficiency Presenting as Autism Spectrum Disorder.

Abstract

To the Editor: A 10-y-old boy with autism spectrum disorder (DSM IV criteria) and normal perinatal history presented to our outpatient clinic for investigation. Evaluation revealed declined fine motor development, moderate language development, repetitive behavior, attention deficit and hyperactivity. Common laboratory tests, electroencephalogram and Magnetic Resonance Imaging (MRI) of the brain were normal. The metabolic screening requested revealed an elevated concent ra t ion of 4-hydroxy-buty r ic ac id in ur ine (60.8 mmol/mol creatinine of urine, normal values: 0). Genetic test revealed two pathogenic mutations in the ALDH5A1 gene, thus confirming diagnosis of succinic semialdehyde dehydrogenase deficiency (SSADHD). Treatment with vigabatrin was initiated without clinical improvement. SSADHD is caused by mutations of the ALDH5A1 gene (6p22), resulting in dysfunction of the enzyme succinic semialdehyde dehydrogenase and accumulation of γ-aminobutyric acid, succinic semialdehyde and γhydroxybutyric acid. Clinical features include intellectual disability, seizures, hypotonia, ataxia and behavioral disturbances. Diagnosis is mainly based on urinary organic acid analysis and genetic testing [1]. MRI of the brain often demonstrates globus pallidii signal changes and cerebellar atrophy [2]. Clinical studies about the impact of vigabatrin, sodium valproate and taurine on clinical aspects of the disease have controversial results [1]. The patient presented autism as the only symptom. This raises the question if metabolic screening should be requested for children with autism spectrum disorder. Schiff et al. found that a routine metabolic screening does not contribute to the causative diagnosis of autism, as the prevalence of inborn metabolic errors in nonsyndromic autism may not be higher than in the general population [3]. On the other hand, in a Greek cohort study of 187 children with confirmed autistic features, who underwent detailed metabolic screening, specific metabolic biomarkers were revealed in 5 of them (2, 7 %) with therapeutic relevance [4]. The underlying cause of autism is often elusive with the exception of recognizable genetic syndromes [3]. The identification of a specific cause at an early age is important for initiating effective individualized intervention and permits genetic counseling. * Maria Gogou mariaangogou@gmail.com