Clinical features and ALDH5A1 gene findings in 13 Chinese cases with succinic semialdehyde dehydrogenase deficiency

Abstract Background and aims: To investigate the clinical features, ALDH5A1gene variations, treatment, and prognosis of patients with succinic semialdehyde dehydrogenase (SSADH) deficiency. Materials and methods: This retrospective study evaluated the findings in 13 Chinese patients with SSADH deficiency admitted to the Pediatric Department of Peking University First Hospital from September 2013 to September 2023. Results: 13 patients (seven male and six female patients; two sibling sisters) were diagnosed as SSADH deficiency aged from 4 months to 15 years. Their urine 4-hydroxybutyrate acid levels were elevated and were accompanied by mildly increased serum lactate levels. Brain MRI showed symmetric abnormal signals in both sides of the globus pallidus and other areas. All 13 patients had psychomotor retardation, with seven showing epileptic seizures. Among the 18 variants of the ALDH5A1 gene identified in these 13 patients, six were previously reported, while 12 were novel variants. Among 12 novel variants, three (c.85_116del, c.206_222dup, c.762C>G) were pathogenic variants; four (c.427delA, c.515G>A, c.755G>T, c.1274T>C) were likely pathogenic; and the remaining five (c.454G>C, c.479C>T, c.637C>T, c.1480G>A, c.1501G>C) were variants of uncertain significance (VUS). The patients received drugs such as L-carnitine, vigabatrin and taurine, along with symptomatic treatment. Their urine 4-hydroxybutyric acid levels showed variable degrees of reduction. Conclusions: A cohort of 13 cases with early-onset SSADH deficiency were analyzed. Onset of symptoms occurred from 1 month to 1 year of age. 12 novel variants were identified from ALDH5A1 Gene.