Novel mutations in two unrelated Italian patients with SSADH deficiency
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Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a rare autosomal recessive disorder of γ-aminobutyric acid (GABA) catabolism caused by mutations in the gene coding for succinic semialdehyde dehydrogenase (ALDH5A1). The abnormal levels of GHB detected in the brain and in all physiological fluids of SSADHD patients represent a diagnostic biochemical hallmark of the disease. Here we report on the clinical and molecular characterization of two unrelated Italian patients and the identification of two novel mutations: a 22 bp DNA duplication in exon 1, c.114_135dup, p.(C46AfsX97), and a non-sense mutation in exon 10, c.1429C > T, p.(Q477X). The two patients showed very different clinical phenotypes, coherent with their age. These findings enrich the characterization of SSADHD families and contribute to the knowledge on the progression of the disease.
KeywordsSSADHD (succinic semialdehyde dehydrogenase deficiency) GABA (γ-aminobutyric acid) GHB (γ-hydroxybutyric acid) ALDH5A1 gene 4-HBA (4-hydroxybutiric aciduria)
The authors would like to thank Cometa Sardegna Onlus Association for its support to the research. We also thank Dr. M. Lo Ponte for the English revision of the manuscript.
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Conflict of interest
The authors declare no conflicts of interests.
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